Synthesis of (-)-Picrotoxinin by Late-Stage Strong Bond Activation

J Am Chem Soc. 2020 Jul 1;142(26):11376-11381. doi: 10.1021/jacs.0c05042. Epub 2020 Jun 23.

Abstract

We report a concise, stereocontrolled synthesis of the neurotoxic sesquiterpenoid (-)-picrotoxinin (1, PXN). The brevity of the route is due to regio- and stereoselective formation of the [4.3.0] bicyclic core by incorporation of a symmetrizing geminal dimethyl group at C5. Dimethylation then enables selective C-O bond formation in multiple intermediates. A series of strong bond (C-C and C-H) cleavages convert the C5 gem-dimethyl group to the C15 lactone of PXN.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Molecular Conformation
  • Picrotoxin / analogs & derivatives*
  • Picrotoxin / chemical synthesis
  • Picrotoxin / chemistry
  • Sesterterpenes
  • Stereoisomerism

Substances

  • Sesterterpenes
  • Picrotoxin
  • picrotoxinin