Total synthesis of (-)-salinosporamide A

Org Lett. 2011 Jun 17;13(12):3028-31. doi: 10.1021/ol200886j. Epub 2011 May 17.

Abstract

A concise and stereoselective total synthesis of (-)-salinosporamide A (1), a potent inhibitor of the 20S proteasome that is in clinical development as an anticancer drug candidate, has been accomplished in 14 steps with 19% overall yield from 4-pentenoic acid. Our synthesis features a stereoselective alkylation utilizing a chiral auxiliary, formation of a pyrrolidine unit, and oxidation of the pyrrolidine to a γ-lactam. To demonstrate the scalability of our synthesis, (-)-salinosporamide A has been synthesized on a gram scale.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Lactones / chemical synthesis*
  • Lactones / chemistry
  • Lactones / pharmacology
  • Molecular Structure
  • Proteasome Inhibitors*
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Lactones
  • Proteasome Inhibitors
  • Pyrroles
  • marizomib