Deracemization of mexiletine biocatalyzed by omega-transaminases.
(S)- as well as (R)-mexiletine [1-(2,6-dimethylphenoxy)-2-propanamine], a chiral orally effective antiarrhythmic agent, was prepared by deracemization starting from the commercially available racemic amine using omega-transaminases in up to >99% ee and conversion with 97% isolated yield by a one-pot two-step procedure. The absolute configuration could be easily switched to the other enantiomer, just by switching the order of the applied transaminases. The cosubstrate pyruvate needed in the first oxidative step was recycled by using an amino acid oxidase.
Koszelewski
Dominik
D
Department of Chemistry, Organic and Bioorganic Chemistry, Research Centre Applied Biocatalysis, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Pressnitz
Desiree
D
Clay
Dorina
D
Kroutil
Wolfgang
W
D000588:Amines / Q000737:chemistry; D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D008801:Mexiletine / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism; D000637:Transaminases / Q000737:chemistry / Q000378:metabolism*
D000588:Amines; D000889:Anti-Arrhythmia Agents; D008801:Mexiletine; D000594:Amino Acid Oxidoreductases; D000637:Transaminases