Deracemisation of α‐Chiral Primary Amines by a One‐Pot, Two‐Step Cascade Reaction Catalysed by ω‐Transaminases

• Published in: European Journal of Organic Chemistry Vol. 2009; no. 14; pp. 2289 - 2292
• Main Authors: Koszelewski, Dominik, Clay, Dorina, Rozzell, David, Kroutil, Wolfgang
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag 01.05.2009; Wiley; Wiley-VCH
• Subjects: Aliphatic compounds; Amines; Asymmetric catalysis; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; Biotransformations; Chemistry; Chemistry, Organic; Deracemisation; Enzymes; Exact sciences and technology; Fundamental and applied biological sciences. Psychology; Methods. Procedures. Technologies; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Enzymes; Amines; ASYMMETRIC-SYNTHESIS; ACIDS; Biotransformations; Deracemisation; Asymmetric catalysis; DYNAMIC KINETIC RESOLUTION; BIOCATALYSIS; INHIBITION; MEXILETINE; VIBRIO-FLUVIALIS JS17; SUBSTRATE; RACEMIZATION; TYPE-1; Chiral compound; Stereoselectivity; Racemic; Biotransformation; Alanine; Catalytic reaction; Enzyme; Transferases; Pyruvate; Ketone; L-Lactate dehydrogenase; Enzymatic method; α-Aminoacid; Optical resolution; Aminoacid; Transaminases; Enantiomeric excess; Oxidoreductases; Primary amine; Successive reaction
• DOI: 10.1002/ejoc.200801265
• ISSN: 1434-193X

Racemic α‐chiral primary amines were deracemised to optically pure amines in up to >99 % conversion and >99 % ee within 48 h. The deracemisation was a result of a stereoinversion of one amine enantiomer; the formal stereoinversion was achieved by a one‐pot, two‐step procedure: in the first step, kinetic resolution of the chiral racemic amine was performed by employing a ω‐transaminase to yield an intermediate ketone and the remaining optically pure amine; in the second step, the ketone intermediate was stereoselectively transformed into the amine by employing alanine as the amine donor and a ω‐transaminase displaying opposite stereopreference than the ω‐transaminase in the first step. In the second step, lactate dehydrogenase was used to remove the side product pyruvate to shift the unfavourable reaction equilibrium to the product side. Depending on the order of the enantiocomplementary enzymes employed in the cascade, the (R), as well as the (S), enantiomer was accessible.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) Deracemisation of racemic α‐chiral primary amines was achieved by a one‐pot, two‐step procedure. In the first step, one amine enantiomer was transformed under kinetic resolution to the corresponding ketone, which was subsequently stereoselectively aminated in the second step with opposite stereopreference. By switching the order of the ω‐transaminases used, both enantiomers were accessible.