Enantioselective Synthesis of α-Thiocarboxylic Acids by Nitrilase Biocatalysed Dynamic Kinetic Resolution of α-Thionitriles |
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Authors: | Kate Lauder Silvia Anselmi Dr James D Finnigan Dr Yuyin Qi Dr Simon J Charnock Dr Daniele Castagnolo |
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Institution: | 1. School of Cancer and Pharmaceutical Sciences, King's College London, 150 Stamford Street, SE1 9NH London, UK;2. Prozomix Limited, West End Industrial Estate, Haltwhistle, Northumberland, NE49 9HA UK |
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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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Keywords: | biocatalysis dynamic kinetic resolution nitrilase thiocarboxylic acid thionitrile |
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