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Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols
Author(s) -
Li DanYang,
Lou YuJiao,
Xu Jian,
Chen XiaoYang,
Lin XianFu,
Wu Qi
Publication year - 2021
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.202001367
Subject(s) - candida antarctica , chemistry , kinetic resolution , stereoselectivity , stereospecificity , methanol , lipase , stereochemistry , mutant , rational design , electronic effect , catalysis , organic chemistry , enzyme , enantioselective synthesis , nanotechnology , biochemistry , materials science , gene
Herein, we developed an electronic effect‐guided rational design strategy to enhance the enantioselectivity of Candida antarctica lipase B (CALB) mutants towards bulky pyridyl(phenyl)methanols. Compared to W104A mutant previously reported with reversed S ‐stereoselectivity toward sec ‐alcohols, three mutants (W104C, W104S and W104T) displayed significant improvement of S ‐enantioselectivity in the kinetic resolution (KR) of various phenyl pyridyl methyl acetates due to the increased electronic effects between pyridyl and polar residues. The electronic effects were also observed when mutating other residues surrounding the stereospecificity pocket of CALB, such as T42A, S47A, A281S or A281C, and can be used to manipulate the stereoselectivity. A series of bulky pyridyl(phenyl) methanols, including S ‐(4‐chlorophenyl)(pyridin‐2‐yl) methanol ( S ‐CPMA), the intermediate of bepotastine, were obtained in good yields and ee values.