Enantioselective Synthesis of α‐Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α‐Thionitriles

Lauder, Kate; Anselmi, S; Finnigan, James; Qi, Yuyin; Charnock, Simon J.; Castagnolo, Daniele

doi:10.1002/chem.202001108

Cited by 9 publications

(2 citation statements)

References 35 publications

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“…In 2020, Castagnolo and co-workers reported the transformation of racemic thionitriles to α-thioacids through DKR-based hydrolysis with nitrilases (Scheme 20). 51 The labile αstereocenter of the thionitrile substrate readily epimerizes under mild conditions, followed by preferential hydrolysis of one enantiomer by the nitrilase. Among the 35 nitrilases tested, enzymes Nit27 and Nit34 were found to efficiently catalyze the DKR of racemic α-thionitriles under mild conditions, affording the corresponding carboxylic acids with good conversions (24−83% yield) and good-to-excellent enantioselectivity (61− 99% ee).…”

Section: Dkr Of Carbonyl Compounds With Labilementioning

confidence: 99%

Recent Progress and Developments in Chemoenzymatic and Biocatalytic Dynamic Kinetic Resolution

Yang

Deng

Renata

2022

Org. Process Res. Dev.

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Dynamic kinetic resolution (DKR) is a powerful method to construct complex molecules with one or more stereocenters. In light of their exquisite stereospecificity and stereoselectivity, enzymes are becoming widely used as catalysts in DKR. This review summarizes chemoenzymatic and biocatalytic methodologies for DKR that have been developed in the past decade. Additionally, applications of these methodologies in the preparation of active pharmaceutical ingredients and emerging paradigms, including the combined use of biocatalysis and photocatalysis for DKR, are highlighted.

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Section: Dkr Of Carbonyl Compounds With Labilementioning

confidence: 99%

Recent Progress and Developments in Chemoenzymatic and Biocatalytic Dynamic Kinetic Resolution

Yang

Deng

Renata

2022

Org. Process Res. Dev.

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“…Following up on our studies on the synthesis of chiral sulfur compounds via biocatalysis, 19 herein, we report the preparation, screening, and development of novel MsrA biocatalysts from different microorganisms. Moreover, through a combination of in silico docking and molecular dynamics, protein NMR, and rational mutagenesis studies, a library of MsrA mutant enzymes has been rationally designed and prepared.…”

Section: Introductionmentioning

confidence: 99%

Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides

et al. 2023

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Methionine sulfoxide reductase A (MsrA) enzymes have recently found applications as nonoxidative biocatalysts in the enantioselective kinetic resolution of racemic sulfoxides. This work describes the identification of selective and robust MsrA biocatalysts able to catalyze the enantioselective reduction of a variety of aromatic and aliphatic chiral sulfoxides at 8–64 mM concentration with high yields and excellent ees (up to 99%). Moreover, with the aim to expand the substrate scope of MsrA biocatalysts, a library of mutant enzymes has been designed via rational mutagenesis utilizing in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies. The mutant enzyme MsrA33 was found to catalyze the kinetic resolution of bulky sulfoxide substrates bearing non-methyl substituents on the sulfur atom with ees up to 99%, overcoming a significant limitation of the currently available MsrA biocatalysts.

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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

et al. 2022

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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 CÀ 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 CÀ S bond with opposite enantioselectivities by dynamic kinetic resolution (DKR) of racemic α-thioaldehydes.

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Enantioselective Synthesis of α‐Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α‐Thionitriles

Cited by 9 publications

References 35 publications

Recent Progress and Developments in Chemoenzymatic and Biocatalytic Dynamic Kinetic Resolution

Recent Progress and Developments in Chemoenzymatic and Biocatalytic Dynamic Kinetic Resolution

Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides

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

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