Preparing β-blocker (R)-Nifenalol based on enantioconvergent synthesis of (R)-p-nitrophenylglycols in continuous packed bed reactor with epoxide hydrolase

被引：4

作者：

Li, Fu-Long ^{[1
]}

Zheng, Yu-Cong ^{[1
]}

Li, Hao ^{[1
]}

Chen, Fei-Fei ^{[1
]}

Yu, Hui-Lei ^{[1
]}

Xu, Jian-He ^{[1
]}

机构：

[1] East China Univ Sci & Technol, Shanghai Collaborat Innovat Ctr Biomfg, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China

来源：

TETRAHEDRON | 2019年 / 75卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Vigna radiate epoxide hydrolase; Enantioconvergent hydrolysis; Immobilized enzyme; Packed bed reactor; (R)-Nifenalol; MICROBIOLOGICAL TRANSFORMATIONS; HYDROLYSIS; RESOLUTION; REDUCTION; COMPLEXES; OXIDE; ACID;

D O I：

10.1016/j.tet.2019.01.034

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An engineered epoxide hydrolase from Vigna radiate (VrEH2(M263N)) shows near-perfect enantioconvergence in single enzyme mediated hydrolysis of racemic p-nitrostyrene oxide (pNSO). To explore industrial potential of the promising biocatalyst, we tried to immobilize the VrEH2 variant by covalently linking onto a commercially available amino resin ECR8405F. Then a 5-mL packed bed reactor filled with the immobilized VrEH2(M263N) was connected with macroporous resin NKA-11 for in situ product adsorption, and the product (R)-p-nitrophenyl glycol (pNPG) was harvested by methanol elution, with 91% isolated yield and 97% ee. The continuous reactor was operated stably for more than 100 h with a space time yield of 20 g.L-1.h(-1). Subsequently, the beta-blocker (R)-Nifenalol was prepared by chemically synthesized from (R)-pNPG, affording the product in an overall yield of 61.3% (1.5 g) and an enantiopurity of 99.9% ee after recrystallization. (C) 2019 Published by Elsevier Ltd.

引用

页码：1706 / 1710

页数：5

共 31 条

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