Deracemization of mexiletine biocatalyzed by omega-transaminases

Org Lett. 2009 Nov 5;11(21):4810-2. doi: 10.1021/ol901834x.

Abstract

(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Amino Acid Oxidoreductases / metabolism*
  • Anti-Arrhythmia Agents / chemical synthesis*
  • Anti-Arrhythmia Agents / chemistry
  • Catalysis
  • Mexiletine / chemical synthesis*
  • Mexiletine / chemistry
  • Molecular Structure
  • Stereoisomerism
  • Transaminases / chemistry
  • Transaminases / metabolism*

Substances

  • Amines
  • Anti-Arrhythmia Agents
  • Mexiletine
  • Amino Acid Oxidoreductases
  • Transaminases