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酮还原酶在药物和生物活性分子的不对称合成中的应用:最新进展(2018-2020)。

Application of Ketoreductase in Asymmetric Synthesis of Pharmaceuticals and Bioactive Molecules: An Update (2018-2020).

机构信息

Department of Chemistry, Engineering Center of Catalysis and Synthesis for Chiral Molecules, Fudan University, Shanghai Engineering Research Center of Industrial Asymmetric Catalysis of Chiral Drugs, 220 Handan Road, Shanghai, 200433, P. R. China.

出版信息

Chem Rec. 2021 Jul;21(7):1611-1630. doi: 10.1002/tcr.202100062. Epub 2021 Apr 9.

Abstract

With the rapid development of genomic DNA sequencing, recombinant DNA expression, and protein engineering, biocatalysis has been increasingly and widely adopted in the synthesis of pharmaceuticals, bioactive molecules, fine chemicals, and agrochemicals. In this review, we have summarized the most recent advances achieved (2018-2020) in the research area of ketoreductase (KRED)-catalyzed asymmetric synthesis of chiral secondary alcohol intermediates to pharmaceuticals and bioactive molecules. In the first part, synthesis of chiral alcohols with one stereocenter through the bioreduction of four different ketone classes, namely acyclic aliphatic ketones, benzyl or phenylethyl ketones, cyclic aliphatic ketones, and aryl ketones, is discussed. In the second part, KRED-catalyzed dynamic reductive kinetic resolution and reductive desymmetrization are presented for the synthesis of chiral alcohols with two contiguous stereocenters.

摘要

随着基因组 DNA 测序、重组 DNA 表达和蛋白质工程的快速发展,生物催化在药物、生物活性分子、精细化学品和农用化学品的合成中得到了越来越广泛的应用。在这篇综述中,我们总结了(2018-2020 年)在酮还原酶(KRED)催化的手性仲醇中间体不对称合成药物和生物活性分子的研究领域中取得的最新进展。在第一部分中,讨论了通过生物还原四种不同酮类,即无环脂肪族酮、苄基或苯乙基酮、环脂肪族酮和芳基酮,合成具有一个手性中心的手性醇。在第二部分,介绍了 KRED 催化的动态还原动力学拆分和还原去对称化反应在手性具有两个连续手性中心的醇的合成中的应用。

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