高立体选择性合成大体积二芳基和脂肪族二醇的工程尺寸-互补醇脱氢酶突变体

IF 4.7 1区化学 Q1 CHEMISTRY, ORGANIC

Organic Letters Pub Date : 2026-10-19 DOI:10.1021/acs.orglett.6c03975

Cheng-Long Xu,Lin-Lin Song,Meng-Jiao Li,Shu-Yun Ju,Zhe Dou,Ya-Jun Wang

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引用次数: 0

摘要

手性1,4-二醇是制药工业中重要的中间体，但其不对称合成仍然具有挑战性。通过醇脱氢酶的大小互补工程，合成了具有高立体选择性的大体积二芳基和脂肪族手性1,4-二醇。突变体M5对1,4-二苯基-1,4-丁二酮的催化效率提高了181倍，而突变体N2对(2S,5S)-己二醇的时空产率为1065 g L-1 d-1。这项工作为获取大体积二芳基和脂肪族二醇提供了一个有价值的平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Engineering Size-Complementary Alcohol Dehydrogenase Mutants for Highly Stereoselective Synthesis of Bulky Diaryl and Aliphatic Diols

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Engineering Size-Complementary Alcohol Dehydrogenase Mutants for Highly Stereoselective Synthesis of Bulky Diaryl and Aliphatic Diols

Chiral 1,4-diols serve as crucial intermediates in the pharmaceutical industry, yet their asymmetric synthesis remains challenging. Through size-complementary engineering of alcohol dehydrogenase from Saccharomyces kudriavzevii, bulky diaryl and aliphatic chiral 1,4-diols were synthesized with high stereoselectivity. Mutant M5 showed a 181-fold enhancement in catalytic efficiency toward 1,4-diphenyl-1,4-butanedione, whereas mutant N2 delivered a space–time yield of 1065 g L–1 d–1 for (2S,5S)-hexanediol. This work provides a valuable platform for accessing bulky diaryl and aliphatic diols.

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来源期刊

Organic Letters 化学-有机化学

CiteScore

9.30

自引率

11.50%

发文量

1607

审稿时长

1.5 months

期刊介绍： Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.