Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols
Abstract 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 ‐alcoh...
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Online Access: | http://dx.doi.org/10.1002/adsc.202001367 https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.202001367 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/adsc.202001367 |
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crwiley:10.1002/adsc.202001367 2024-06-02T07:58:21+00:00 Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols Li, Dan‐Yang Lou, Yu‐Jiao Xu, Jian Chen, Xiao‐Yang Lin, Xian‐Fu Wu, Qi National Natural Science Foundation of China Natural Science Foundation of Zhejiang Province 2021 http://dx.doi.org/10.1002/adsc.202001367 https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.202001367 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/adsc.202001367 en eng Wiley http://onlinelibrary.wiley.com/termsAndConditions#vor Advanced Synthesis & Catalysis volume 363, issue 7, page 1867-1872 ISSN 1615-4150 1615-4169 journal-article 2021 crwiley https://doi.org/10.1002/adsc.202001367 2024-05-03T11:06:06Z Abstract 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. magnified image Article in Journal/Newspaper Antarc* Antarctica Wiley Online Library Advanced Synthesis & Catalysis 363 7 1867 1872 |
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Wiley Online Library |
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language |
English |
description |
Abstract 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. magnified image |
author2 |
National Natural Science Foundation of China Natural Science Foundation of Zhejiang Province |
format |
Article in Journal/Newspaper |
author |
Li, Dan‐Yang Lou, Yu‐Jiao Xu, Jian Chen, Xiao‐Yang Lin, Xian‐Fu Wu, Qi |
spellingShingle |
Li, Dan‐Yang Lou, Yu‐Jiao Xu, Jian Chen, Xiao‐Yang Lin, Xian‐Fu Wu, Qi Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols |
author_facet |
Li, Dan‐Yang Lou, Yu‐Jiao Xu, Jian Chen, Xiao‐Yang Lin, Xian‐Fu Wu, Qi |
author_sort |
Li, Dan‐Yang |
title |
Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols |
title_short |
Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols |
title_full |
Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols |
title_fullStr |
Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols |
title_full_unstemmed |
Electronic Effect‐Guided Rational Design of Candida antarctica Lipase B for Kinetic Resolution Towards Diarylmethanols |
title_sort |
electronic effect‐guided rational design of candida antarctica lipase b for kinetic resolution towards diarylmethanols |
publisher |
Wiley |
publishDate |
2021 |
url |
http://dx.doi.org/10.1002/adsc.202001367 https://onlinelibrary.wiley.com/doi/pdf/10.1002/adsc.202001367 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/adsc.202001367 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Advanced Synthesis & Catalysis volume 363, issue 7, page 1867-1872 ISSN 1615-4150 1615-4169 |
op_rights |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
op_doi |
https://doi.org/10.1002/adsc.202001367 |
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Advanced Synthesis & Catalysis |
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363 |
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7 |
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1867 |
op_container_end_page |
1872 |
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1800741663359893504 |