Synthesis of chamaecypanone C analogues from in situ-generated cyclopentadienones and their biological evaluation

J Am Chem Soc. 2012 Dec 5;134(48):19782-7. doi: 10.1021/ja3084708. Epub 2012 Nov 20.

Abstract

A rhodium-catalyzed dehydrogenation protocol for the conversion of 3,5-diarylcyclopentenones to the corresponding 2,4-diarylcyclopentadienones has been developed. With this protocol, analogues of the cytotoxic agent chamaecypanone C have been synthesized via Diels-Alder cycloaddition between the cyclopentadienones and in situ-generated o-quinols. Biological evaluation of these analogues revealed a compound with higher activity as a microtubule inhibitor and cytotoxic agent in comparison with the parent structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bridged Bicyclo Compounds / chemical synthesis*
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / pharmacology*
  • Catalysis
  • Cyclopentanes / chemistry*
  • Cyclopentanes / pharmacology*
  • Microtubules / drug effects
  • Molecular Structure
  • Rhodium / chemistry*
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*

Substances

  • Bridged Bicyclo Compounds
  • Cyclopentanes
  • Tubulin Modulators
  • chamaecypanone C
  • Rhodium