Orchestration of concurrent oxidation and reduction cycles for stereoinversion and deracemisation of sec-alcohols

J Am Chem Soc. 2008 Oct 22;130(42):13969-72. doi: 10.1021/ja804816a. Epub 2008 Sep 27.

Abstract

Black and white are opposites as are oxidation and reduction. Performing an oxidation, for example, of a sec-alcohol and a reduction of the corresponding ketone in the same vessel without separation of the reagents seems to be an impossible task. Here we show that oxidative cofactor recycling of NADP (+) and reductive regeneration of NADH can be performed simultaneously in the same compartment without significant interference. Regeneration cycles can be run in opposing directions beside each other enabling one-pot transformation of racemic alcohols to one enantiomer via concurrent enantioselective oxidation and asymmetric reduction employing defined alcohol dehydrogenases with opposite stereo- and cofactor-preference. Thus, by careful selection of appropriate enzymes, NADH recycling can be performed in the presence of NADP (+) recycling to achieve overall, for example, deracemisation of sec-alcohols or stereoinversion representing a possible concept for a "green" equivalent to the chemical-intensive Mitsunobu inversion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / chemistry
  • Alcohols / chemical synthesis
  • Alcohols / chemistry*
  • Ketones / chemistry
  • Molecular Conformation
  • NAD / chemistry
  • NADP / chemistry
  • Oxidation-Reduction
  • Stereoisomerism

Substances

  • Alcohols
  • Ketones
  • NAD
  • NADP
  • Alcohol Dehydrogenase