Nitrile as activating group in the asymmetric bioreduction of β-cyanoacrylic acids catalyzed by ene-reductases

Abstract

Asymmetric bioreduction of an (E)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(S)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% ee. Deuterium labelling studies showed that the nitrile moiety was the preferred activating/anchor group in the active site of the enzyme over the carboxylic acid or the corresponding methyl ester. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.