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Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High pH Dynamic Kinetic Reduction.

Authors :
Xu, Feng
Kosjek, Birgit
Cabirol, Fabien L.
Chen, Haibin
Desmond, Richard
Park, Jeonghan
Gohel, Anupam P.
Collier, Steven J.
Smith, Derek J.
Liu, Zhuqing
Janey, Jacob M.
Chung, John Y. L.
Alvizo, Oscar
Source :
Angewandte Chemie. 6/4/2018, Vol. 130 Issue 23, p6979-6983. 5p.
Publication Year :
2018

Abstract

Abstract: Described here is an efficient stereoselective synthesis of vibegron enabled by an enzymatic dynamic kinetic reduction that proceeds in a high‐pH environment. To overcome enzyme performance limitations under these conditions, a ketoreductase was evolved by a computationally and structurally aided strategy to increase cofactor stability through tighter binding. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00448249
Volume :
130
Issue :
23
Database :
Academic Search Index
Journal :
Angewandte Chemie
Publication Type :
Academic Journal
Accession number :
129873425
Full Text :
https://doi.org/10.1002/ange.201802791