Biocatalytic organic synthesis of optically pure (S)-scoulerine and berbine and benzylisoquinoline alkaloids

J Org Chem. 2011 Aug 19;76(16):6703-14. doi: 10.1021/jo201056f. Epub 2011 Jul 19.

Abstract

A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4-8 linear steps using either a Bischler-Napieralski cyclization or a C1-Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5-9 linear steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alkaloids / metabolism
  • Benzylisoquinolines / chemical synthesis*
  • Benzylisoquinolines / chemistry
  • Benzylisoquinolines / metabolism
  • Berberine Alkaloids / chemical synthesis*
  • Berberine Alkaloids / chemistry
  • Berberine Alkaloids / metabolism
  • Biocatalysis
  • Cyclization
  • Molecular Structure
  • Organic Chemistry Phenomena
  • Oxidation-Reduction
  • Stereoisomerism

Substances

  • Alkaloids
  • Benzylisoquinolines
  • Berberine Alkaloids
  • discretamine
  • berbine