Nitrile as Activating Group in the Asymmetric Bioreduction of β‐Cyanoacrylic Acids Catalyzed by Ene‐Reductases

Abstract

Asymmetric bioreduction of an (<i>E</i>)-β-cyano-2,4-dienoic acid derivative by ene-reductases allowed a shortened access to a precursor of pregabalin [(<i>S</i>)-3-(aminomethyl)-5-methylhexanoic acid] possessing the desired configuration in up to 94% conversion and >99% <i>ee</i>. 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.