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

Kate Lauder; Silvia Anselmi; James D. Finnigan; Yuyin Qi; Simon J. Charnock; Daniele Castagnolo

doi:10.1002/chem.202001108

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

Kate Lauder, Silvia Anselmi, James D. Finnigan, Yuyin Qi, Simon J. Charnock, Daniele Castagnolo^*

^*Corresponding author for this work

Institute of Pharmaceutical Science

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

The enantioselective synthesis of α-thiocarboxylic acids by biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyse the DKR of racemic α-thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good-to-excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base.

Original language	English
Pages (from-to)	10422-10426
Number of pages	5
Journal	Chemistry - A European Journal
Volume	26
Issue number	46
DOIs	https://doi.org/10.1002/chem.202001108
Publication status	Published - 17 Aug 2020

Keywords

biocatalysis
dynamic kinetic resolution
nitrilase
thiocarboxylic acid
thionitrile

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10.1002/chem.202001108

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abstract = "The enantioselective synthesis of α-thiocarboxylic acids by biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyse the DKR of racemic α-thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good-to-excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base.",

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author = "Kate Lauder and Silvia Anselmi and Finnigan, {James D.} and Yuyin Qi and Charnock, {Simon J.} and Daniele Castagnolo",

year = "2020",

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T1 - Enantioselective Synthesis of α-Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α-Thionitriles

AU - Lauder, Kate

AU - Anselmi, Silvia

AU - Finnigan, James D.

AU - Qi, Yuyin

AU - Charnock, Simon J.

AU - Castagnolo, Daniele

PY - 2020/8/17

Y1 - 2020/8/17

N2 - The enantioselective synthesis of α-thiocarboxylic acids by biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyse the DKR of racemic α-thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good-to-excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base.

AB - The enantioselective synthesis of α-thiocarboxylic acids by biocatalytic dynamic kinetic resolution (DKR) of nitrile precursors exploiting nitrilase enzymes is described. A panel of 35 nitrilase biocatalysts were screened and enzymes Nit27 and Nit34 were found to catalyse the DKR of racemic α-thionitriles under mild conditions, affording the corresponding carboxylic acids with high conversions and good-to-excellent ee. The ammonia produced in situ during the biocatalytic transformation favours the racemization of the nitrile enantiomers and, in turn, the DKR without the need of any external additive base.

KW - biocatalysis

KW - dynamic kinetic resolution

KW - nitrilase

KW - thiocarboxylic acid

KW - thionitrile

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U2 - 10.1002/chem.202001108

DO - 10.1002/chem.202001108

M3 - Article

AN - SCOPUS:85088126253

SN - 0947-6539

VL - 26

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JO - Chemistry (Weinheim an der Bergstrasse, Germany)

JF - Chemistry (Weinheim an der Bergstrasse, Germany)

IS - 46

ER -

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

Abstract

Keywords

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