Toward the synthesis of thapsigargin: enantioselective synthesis of 7,11-dihydroxyguaianolides

Org Lett. 2006 Jun 22;8(13):2879-82. doi: 10.1021/ol061024z.

Abstract

[reaction: see text] The enantioselective synthesis of a 7,11-dihydroxyguaianolide bearing the stereochemistry present in thapsigargin, a potent and selective inhibitor of the Ca(2+) SERCA-ATPase pumps, is described. Starting from (+)-dihydrocarvone, the synthesis presents two key steps. The first one involves the photochemical rearrangement of a gamma,delta-unsaturated ketone eudesmane into the corresponding guaiane. The second step consists of the regioselective oxidation of an unprotected tetrahydroxylated ketone to provide a dihydroxylactone with the required stereochemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Molecular Structure
  • Sesquiterpenes, Guaiane / chemical synthesis*
  • Sesquiterpenes, Guaiane / chemistry
  • Stereoisomerism
  • Thapsia / chemistry
  • Thapsigargin / chemical synthesis*

Substances

  • Sesquiterpenes, Guaiane
  • Thapsigargin