Highly diastereo- and enantioselective catalytic synthesis of the bis-tetrahydrofuran alcohol of Brecanavir and Darunavir

Black, David M.; Davis, Roman; Doan, Brian D.; Lovelace, Tom; Millar, Alan; Toczko, Jennifer F.; Xie, Shiping

doi:10.1016/j.tetasy.2008.07.037

Cited by 25 publications

(18 citation statements)

References 31 publications

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“…While syntheses of both groups are relatively efficient due to the overall short synthetic sequences, enzymatic enhancements are still required to obtain bis-THF alcohol 1′ with sufficient enantiomeric purity. Few examples of highly enantio- and diastereoselective syntheses of bis-THF alcohol 1′ through chiral catalysis including our own works have been reported. , …”

Section: Introductionmentioning

confidence: 99%

“…Few examples of highly enantio-and diastereoselective syntheses of bis-THF alcohol 1′ through chiral catalysis including our own works have been reported. 8,9 In our previous study, a practical method for the synthesis of bis-THF alcohol 1′ through chiral enamine catalysis was developed (Scheme 1, our first generation). 9 The route is based on an enantioselective proline catalyzed direct cross aldol reaction between aldehydes 10 to give predominantly Anti-4 followed by cyclization and TEMPO oxidation to afford ketone 5, which is reduced diastereoselectively to give bis-THF alcohol 1′ in an optically pure form.…”

Section: ■ Introductionmentioning

confidence: 99%

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Research and Development of an Efficient Synthesis of a Key Building Block for Anti-AIDS Drugs by Diphenylprolinol-Catalyzed Enantio- and Diastereoselective Direct Cross Aldol Reaction

Hayashi

Aikawa

Shimasaki

et al. 2016

Org. Process Res. Dev.

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An efficient method for synthesizing 1-({[(3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-yloxy]carbonyl}oxy)pyrrolidine-2,5-dione (1), a key building block for HIV protease inhibitors, has been developed. A diphenylprolinol-catalyzed highly enantio- and diastereoselective cross aldol reaction of polymeric ethyl glyoxylate with an aldehyde was used as the key step. Acetalized aldol adduct was reduced with NaBH4 to give the diol intermediate in quantitative yield. The acetal exchange reaction followed by hydrogenation with Pd/C catalyst afforded 1′ in 95% yield over 2 steps. The condensation of 1′ with a carbonate gave crystalline 1 (>99/1 dr, > 99% ee) after single crystallization. This is a highly practical synthetic method since environmentally benign organocatalysis is utilized, the amount of catalyst is reduced to 3 mol %, and all of the intermediates before 1′ can be used without any purification.

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Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

Research and Development of an Efficient Synthesis of a Key Building Block for Anti-AIDS Drugs by Diphenylprolinol-Catalyzed Enantio- and Diastereoselective Direct Cross Aldol Reaction

Hayashi

Aikawa

Shimasaki

et al. 2016

Org. Process Res. Dev.

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“… 40 This strategy was applied to the synthesis of bis-tetrahydrofuran alcohol 25 with excellent diastereoselectivity (dr = 98:2) and enantioselectivity (94% ee), which provided an important structural moiety present in several protease inhibitors including darunavir. 68 …”

Section: Furanone-derived Enolates As Nucleophilesmentioning

confidence: 99%

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

2017

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γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials.

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“…4 This explains why numerous routes for its synthesis have been described. 2,3,[4][5][6][7][8][9][10][11][12][13] In this study we have assessed the greenness and sustainability of the three most recent and innovative routes. 3,4,13 Publication in 1992 of the amounts of waste generated per kg of product (The (E)nvironmental Factor), in various sectors of the chemical industry (Table 1), 14 served to focus attention on the high E-factors observed in pharmaceuticals manufacture.…”

Section: Introductionmentioning

confidence: 99%

Comparing the greenness and sustainability of three routes to an HIV protease inhibitor intermediate

2021

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Highly diastereo- and enantioselective catalytic synthesis of the bis-tetrahydrofuran alcohol of Brecanavir and Darunavir

Cited by 25 publications

References 31 publications

Research and Development of an Efficient Synthesis of a Key Building Block for Anti-AIDS Drugs by Diphenylprolinol-Catalyzed Enantio- and Diastereoselective Direct Cross Aldol Reaction

Research and Development of an Efficient Synthesis of a Key Building Block for Anti-AIDS Drugs by Diphenylprolinol-Catalyzed Enantio- and Diastereoselective Direct Cross Aldol Reaction

Catalytic Asymmetric Synthesis of Butenolides and Butyrolactones

Comparing the greenness and sustainability of three routes to an HIV protease inhibitor intermediate

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