文献类型：期刊文献

英文题名：Dual-Enzyme Catalyzed Stereoselective Synthesis of Chiral Aromatic Polysubstituted γ-Butyrolactones

作者：Chu, Liliang[1];Zhang, Xiaoyan[1];Fan, Daidi[2];Bai, Yunpeng[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Northwest Univ, Shaanxi R&D Ctr Biomat & Fermentat Engn, Sch Chem Engn, Xian 710069, Shaanxi, Peoples R China

年份：2024

卷号：14

期号：23

起止页码：17276

外文期刊名：ACS CATALYSIS

收录：;EI(收录号：20244717400390);WOS:【SCI-EXPANDED(收录号:WOS:001352418300001)】；

基金：This work was financially sponsored by the National Key R&D Program of China (grant nos. 2021YFC2102800 and 2023YFA0913600), the National Natural Science Foundation of China (grant nos. 22078096 and 22378120).

语种：英文

外文关键词：enzyme catalysis; cascade reaction; ene reductase; carbonyl reductase; directed evolution; polysubstituted gamma-butyrolactones

摘要：Chiral polysubstituted aromatic gamma-butyrolactones are core structural units of many natural products and high value-added chemicals in the pharmaceutical and food industries. Currently, the precise construction of multiple chiral centers on the five-membered heterocycle substituted by bulky phenyl groups faces big challenges, such as low stereoselectivity, expensive noble metal catalysts, harsh reaction conditions and low atom economy. Herein, we report a one-pot, two-enzyme catalytic strategy for the synthesis of 18 bulky di/trisubstituted aromatic gamma-butyrolactones on the alpha-, beta- and gamma-carbons with good enantioselectivities (up to >99% ee) and diastereoselectivities (up to >99:1 dr). This cascade process includes sequential two-step asymmetric reduction of alpha-/beta-unsaturated gamma-ketoesters by four ene reductases and a carbonyl reductase without intermediate isolation and catalyst removal. In particular, the large sterically hindered substrates (1p-1s) were converted to the corresponding trisubstituted gamma-butyrolactones (4p-4s) with 98-99% ee and >99:1 dr. This enzymatic cascade process represents a simple, atom-economic and enantioselective method to deliver a broad of bulky polysubstituted gamma-butyrolactones in a cheap and efficient manner compared to conventional methods.