Total Synthesis of Celastrol, Development of a Platform to Access Celastroid Natural Products

J Am Chem Soc. 2015 Sep 23;137(37):11864-7. doi: 10.1021/jacs.5b06261. Epub 2015 Sep 10.

Abstract

Celastroid natural products, triterpenes, have been and continue to be investigated in clinical trials. Celastrol, and for that matter any member of the celastroid family, was prepared for the first time through chemical synthesis starting from 2,3-dimethylbutadiene. A triene cyclization precursor generated in 12 steps underwent a nonbiomimetic polyene cyclization mediated by ferric chloride to generate the generic celastroid pentacyclic core. In the cyclization, engagement of a tetrasubstituted olefin formed adjacent all carbon quaternary centers stereospecifically. With access to the carbocyclic core of the family of natural products, wilforic acid and wilforol A were prepared en route to racemic celastrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Products / chemical synthesis*
  • Biological Products / chemistry
  • Chemistry Techniques, Synthetic
  • Triterpenes / chemical synthesis*
  • Triterpenes / chemistry

Substances

  • Biological Products
  • Triterpenes
  • celastrol