Chemoenzymatic synthesis of (2S)-2-arylpropanols through a dynamic kinetic resolution of 2-arylpropanals with alcohol dehydrogenases

Org Biomol Chem. 2010 Sep 21;8(18):4117-23. doi: 10.1039/c005098a. Epub 2010 Jul 13.

Abstract

We applied Horse Liver Alcohol Dehydrogenase (HLADH) to the enantioselective synthesis of six (2S)-2-arylpropanols, useful intermediates in the synthesis of Profens. The influence of substrate structure and reaction conditions on yields and enantioselectivity were investigated. The high yields and high enantioselectivity towards the (S)-enantiomer obtained in the bioreduction of 2-arylpropionic aldehydes, clearly indicate the achievement of a DKR process through a combination of an enzyme-catalyzed kinetic reduction with a chemical base-catalyzed racemization of the unreacted aldehydes. The racemization step is represented by the keto-enol equilibrium of the aldehyde and can be controlled by modulating pH and reaction conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / chemistry
  • Alcohol Dehydrogenase / metabolism*
  • Aldehydes / chemistry*
  • Animals
  • Biocatalysis
  • Horses
  • Hydrogen-Ion Concentration
  • Kinetics
  • Liver / enzymology*
  • Molecular Structure
  • Propanols / chemical synthesis*
  • Propanols / chemistry*
  • Stereoisomerism

Substances

  • Aldehydes
  • Propanols
  • Alcohol Dehydrogenase