Synthesis of α,β-unsaturated esters via a chemo-enzymatic chain elongation approach by combining carboxylic acid reduction and Wittig reaction.
Synthesis of α,β-unsaturated esters via a chemo-enzymatic chain elongation approach by combining carboxylic acid reduction and Wittig reaction.
复制标题
DOI：
10.3762/bjoc.11.243
复制
发表时间：
2015
影响因子：
2.7
通讯作者：
Zhu D
中科院分区：
文献类型：
--
作者：
Duan Y;Yao P;Du Y;Feng J;Wu Q;Zhu D
α，β-不饱和酯是有机合成的通用结构单元，在工业应用中具有重要意义。人们已经开发了各种各样的合成方法，其中相当多的方法使用醛作为前体。本文报道了一种通过酶促羧酸还原和Wittig反应相结合的化学-酶促链延长方法来获得α，β-不饱和酯。最近，我们发现分枝杆菌能够将苯乙酸（1a）还原为2-苯基-1-乙醇（1c），并且分枝杆菌基因组中的两个序列与来自爱荷华诺卡氏菌的羧酸还原酶（CAR）基因具有高度同源性。这两个推定的CAR基因被克隆并在大肠杆菌中过表达。大肠杆菌中的两种蛋白质中的一种可以降低1a。对重组CAR进行纯化和表征。该酶对包括布洛芬在内的多种芳香族和脂肪族羧酸表现出高活性。分枝杆菌CAR催化羧酸还原生成醛，然后通过Wittig反应生成两个碳原子延伸的α，β-不饱和酯，为这些重要化合物的合成提供了一种新的化学-酶法。
α,β-Unsaturated esters are versatile building blocks for organic synthesis and of significant importance for industrial applications. A great variety of synthetic methods have been developed, and quite a number of them use aldehydes as precursors. Herein we report a chemo-enzymatic chain elongation approach to access α,β-unsaturated esters by combining an enzymatic carboxylic acid reduction and Wittig reaction. Recently, we have found that Mycobacterium sp. was able to reduce phenylacetic acid (1a) to 2-phenyl-1-ethanol (1c) and two sequences in the Mycobacterium sp. genome had high identity with the carboxylic acid reductase (CAR) gene from Nocardia iowensis. These two putative CAR genes were cloned, overexpressed in E. coli and one of two proteins could reduce 1a. The recombinant CAR was purified and characterized. The enzyme exhibited high activity toward a variety of aromatic and aliphatic carboxylic acids, including ibuprofen. The Mycobacterium CAR catalyzed carboxylic acid reduction to give aldehydes, followed by a Wittig reaction to afford the products α,β-unsaturated esters with extension of two carbon atoms, demonstrating a new chemo-enzymatic method for the synthesis of these important compounds.