Stereoselectivity-Tailored, Metal-Free Hydrolytic Dynamic Kinetic Resolution of Morita-Baylis-Hillman Acetates Using an Engineered Lipase-Organic Base Cocatalyst
Stereoselectivity-Tailored, Metal-Free Hydrolytic Dynamic Kinetic Resolution of Morita-Baylis-Hillman Acetates Using an Engineered Lipase-Organic Base Cocatalyst
复制标题
使用工程脂肪酶有机碱助催化剂对 Morita-Baylis-Hillman 乙酸酯进行立体选择性定制、无金属水解动态动力学解析
DOI：
10.1021/acscatal.7b01400
复制
发表时间：
2017-07-01
期刊：
影响因子：
12.9
通讯作者：
Wu, Qi
中科院分区：
文献类型：
--
作者：
Xia, Bo;Xu, Jian;Wu, Qi
以三乙胺（TEA）为外消旋催化剂，以野生型或工程化脂肪酶B（CALB）为立体选择性决定催化剂，建立了Morita-Baylis-Hillman（MBH）乙酸酯的无金属对映互补水解动力学拆分方法，得到了具有R或S构型的手性MBH醇.在TEA-WT CALB催化体系中，WT CALB对一系列MBH乙酸酯显示出优异的S对映选择性（高达96%ee和98%转化率）。有利于（R）-MBH醇的对映体选择性的恢复（95%ee; 95%转化率）通过产生由少于20种变体组成的聚焦位点特异性诱变文库来实现。分子模型解释了立体选择性的起源。
Metal-free enantiocomplementary hydrolytic dynamic kinetic resolution of Morita-Baylis-Hillman (MBH) acetates was developed using triethylamine (TEA) as a racemization catalyst and wild-type or engineered lipase B from Candida antarctica (CALB) as stereoselectivity-determining catalyst, leading to chiral MBH alcohols with tailor-made R or S configurations on an optional basis. In the TEA-WT CALB catalysis system, WT CALB displays excellent S enantioselectivity for a series of MBH acetates tested (up to 96% ee and 98% conversion). Reversal of enantioselectivity in favor of (R)-MBH alcohols (95% ee; 95% conversion) was achieved by generating a focused site-specific mutagenesis library composed of less than 20 variants. Molecular modeling explains the origin of stereoselectivity.