Synthesis of (±)-7-hydroxylycopodine

J Org Chem. 2012 Sep 7;77(17):7143-56. doi: 10.1021/jo300353t. Epub 2012 Mar 30.

Abstract

A seven-step synthesis of (±)-7-hydroxylycopodine that proceeds in 5% overall yield has been achieved. The key step is a Prins reaction in 60% sulfuric acid that gave the key tricyclic intermediate with complete control of the ring fusion stereochemistry. A one-pot procedure orthogonally protected the primary alcohol as an acetate and the tertiary alcohol as a methylthiomethyl ether. The resulting product was converted to 7-hydroxydehydrolycopodine by heating with KO-t-Bu and benzophenone in benzene followed by acidic workup. During unsuccessful attempts to make optically pure starting material, we observed the selective Pt-catalyzed hydrogenation of the 5-phenyl group of a 4,5-diphenyloxazolidine under acidic conditions and the Pt-catalyzed isomerization of the oxazolidine to an amide under neutral conditions. In attempts to hydroxylate the starting material so that we could adapt this synthesis to the preparation of (±)-7,8-dihydroxylycopodine (sauroine) we observed the novel oxidation of a bicyclic vinylogous amide to a keto pyridine with Mn(OAc)(3) and to an amino phenol with KHMDS and oxygen.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkaloids / chemical synthesis*
  • Alkaloids / chemistry
  • Molecular Structure
  • Quinolizines / chemical synthesis*
  • Quinolizines / chemistry
  • Stereoisomerism

Substances

  • 7-hydroxylycopodine
  • Alkaloids
  • Quinolizines