Oxidoreductase-Catalyzed Synthesis of Chiral Amines,ACS Catalysis

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Oxidoreductase-Catalyzed Synthesis of Chiral Amines
ACS Catalysis ( IF 11.3 ) Pub Date : 2018-10-16 00:00:00 , DOI: 10.1021/acscatal.8b02924
Mahesh D. Patil ₁ , Gideon Grogan ₂ , Andreas Bommarius ₃ , Hyungdon Yun ₁

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Chiral amines are valuable constituents of many important pharmaceutical compounds and their intermediates. It is estimated that ∼40%–45% of small molecule pharmaceuticals contain chiral amine scaffolds in their structures. The major challenges encountered in the chemical synthesis of enantiopure amines are the use of toxic chemicals, the formation of a large number of byproducts, and multistep syntheses. To address these limitations, cost-effective biocatalytic methods are maturing and proving to be credible alternatives for the synthesis of chiral amines in enantiomerically pure forms. Herein, we report the recent progress achieved and current perspectives in the enzymatic synthesis of chiral amines using four important enzymes, i.e., imine reductases, amine dehydrogenases, monoamine oxidases, and cytochrome P450s. Applications to the industrial synthesis of chiral amines are highlighted. Protein engineering approaches, which play a critical role in improving or altering enzyme activity and substrate scope, are also addressed, along with the discovery of pioneering enzymatic activities from nature. This survey of recent work demonstrates that enzymatic approaches to the synthesis of chiral amines will continue to be a major focus of research in biocatalytic chemistry in the years to come.

中文翻译：

氧化还原酶催化的手性胺的合成

手性胺是许多重要药物化合物及其中间体的有价值的组成部分。据估计，约有40％–45％的小分子药物在其结构中包含手性胺骨架。对映纯胺的化学合成中遇到的主要挑战是使用有毒化学物质，形成大量副产物以及多步合成。为了解决这些限制，具有成本效益的生物催化方法正在成熟，并被证明是合成对映体纯形式的手性胺的可靠替代方法。在本文中，我们报告了使用四种重要的酶即亚胺还原酶，胺脱氢酶，单胺氧化酶和细胞色素P450酶进行手性胺的酶促合成所取得的最新进展和当前的观点。强调了手性胺在工业合成中的应用。还讨论了蛋白质工程方法，这些方法在改善或改变酶活性和底物范围方面起着至关重要的作用，同时还发现了自然界中开创性的酶活性的发现。这项对最近工作的调查表明，合成手性胺的酶学方法将继续是未来几年生物催化化学研究的主要重点。

更新日期：2018-10-16

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