A Formal Synthesis of (-)-Perhydrohistrionicotoxin Using a Cross Metathesis-Hydrogenation Approach

J Org Chem. 2017 Aug 18;82(16):8725-8732. doi: 10.1021/acs.joc.7b01257. Epub 2017 Jul 31.

Abstract

The development of an efficient, high yielding six-step convergent synthesis of the semisynthetic alkaloid (-)-perhydrohistrionicotoxin is described. The key transformations include the cross metathesis of a Brønsted-acid masked primary homoallylic amine with a vinyl cyclohexenone and a regioselective palladium catalyzed hydrogenation. This sequence generated the advanced Winterfeldt spirocyclic precursor in 47% overall yield, with a longest linear sequence of five steps.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amphibian Venoms / chemical synthesis*
  • Amphibian Venoms / chemistry
  • Hydrogenation
  • Molecular Structure
  • Stereoisomerism

Substances

  • Amphibian Venoms
  • perhydrohistrionicotoxin