Exploiting PdII and TiIII chemistry to obtain gamma-dioxygenated terpenoids: synthesis of rostratone and novel approaches to aphidicolin and pyripyropene A

J Org Chem. 2005 Oct 14;70(21):8265-72. doi: 10.1021/jo0502910.

Abstract

In nature there are several terpenoids with a characteristic gamma-dioxygenated system on the A ring, and many of them show interesting pharmacological properties. We have developed a novel strategy for the synthesis of these terpenoids involving three stages: (a) the selective epoxidation of commercial polyenes, (b) titanium(III)-catalyzed cyclization of the epoxypolyprenes thus obtained, and (c) Pd-mediated remote functionalization of the equatorial methyl group attached at C-4 on ring A of the cyclic terpenoid thus formed. This strategy has proved to be useful for the synthesis of the natural labdane rostratone (1) and related terpenoids, as well as for advanced synthetic approaches toward the pharmacologically active products aphidicolin (2) and pyripyropene A (3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Aphidicolin / chemical synthesis*
  • Aphidicolin / chemistry
  • Diterpenes / chemical synthesis*
  • Diterpenes / chemistry
  • Molecular Structure
  • Oxygen / chemistry*
  • Palladium / chemistry*
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Sesquiterpenes / chemical synthesis*
  • Sesquiterpenes / chemistry
  • Terpenes / chemical synthesis*
  • Titanium / chemistry*

Substances

  • Antiviral Agents
  • Diterpenes
  • Pyridines
  • Sesquiterpenes
  • Terpenes
  • rostratone
  • pyripyropene A
  • Aphidicolin
  • Palladium
  • Titanium
  • Oxygen