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Chemoenzymatic Cascades for the Enantioselective Synthesis of β-Hydroxysulfides Bearing a Stereocentre at the C−O or C−S Bond by Ketoreductases

Research output: Contribution to journalArticlepeer-review

Fei Zhao, Kate Lauder, Siyu Liu, James D. Finnigan, Simon J. Charnock, Simon J. Charnock, Daniele Castagnolo

Original languageEnglish
Article numbere202202363
JournalAngewandte Chemie - International Edition
Volume61
Issue number31
DOIs
Accepted/In press2022
Published1 Aug 2022

Bibliographical note

Funding Information: We gratefully acknowledge the K.C. Wong Foundation and BBSRC (iCASE Studentship BB/M016218/1 to K.L.) for financial support. F.Z. gratefully acknowledges the European Commission for the financial support through a Marie Skłodowska-Curie Action Individual Fellowship (BioPhoCS Action with grant agreement ID 838326). Funding Information: We gratefully acknowledge the K.C. Wong Foundation and BBSRC (iCASE Studentship BB/M016218/1 to K.L.) for financial support. F.Z. gratefully acknowledges the European Commission for the financial support through a Marie Skłodowska‐Curie Action Individual Fellowship (BioPhoCS Action with grant agreement ID 838326). Publisher Copyright: © 2022 Wiley-VCH GmbH.

King's Authors

Abstract

Chiral β-hydroxysulfides are an important class of organic compounds which find broad application in organic and pharmaceutical chemistry. Herein we describe the development of novel biocatalytic and chemoenzymatic methods for the enantioselective synthesis of β-hydroxysulfides by exploiting ketoreductase (KRED) enzymes. Four KREDs were discovered from a pool of 384 enzymes identified and isolated through a metagenomic approach. KRED311 and KRED349 catalysed the synthesis of β-hydroxysulfides bearing a stereocentre at the C−O bond with opposite absolute configurations and excellent ee values by novel chemoenzymatic and biocatalytic-chemical-biocatalytic (bio-chem-bio) cascades starting from commercially available thiophenols/thiols and α-haloketones/alcohols. KRED253 and KRED384 catalysed the enantioselective synthesis of β-hydroxysulfides bearing a stereocentre at the C−S bond with opposite enantioselectivities by dynamic kinetic resolution (DKR) of racemic α-thioaldehydes.

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