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

• Published in: Advanced synthesis & catalysis Vol. 356; no. 8; pp. 1878 - 1882
• Main Authors: Winkler, Christoph K., Clay, Dorina, Turrini, Nikolaus G., Lechner, Horst, Kroutil, Wolfgang, Davies, Simon, Debarge, Sebastien, O'Neill, Pat, Steflik, Jeremy, Karmilowicz, Mike, Wong, John W., Faber, Kurt
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 26.05.2014; WILEY‐VCH Verlag
• Subjects: biocatalysis; cyanoacrylates; CC reduction; ene-reductases; pregabalin; Updates; pregabalin; cyanoacrylates; C=C reduction; ene-reductases; biocatalysis
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201301055

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.