Improved total synthesis of the potent HDAC inhibitor FK228 (FR-901228)

Org Lett. 2008 Feb 21;10(4):613-6. doi: 10.1021/ol702957z. Epub 2008 Jan 19.

Abstract

A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key beta-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone.

Publication types

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

MeSH terms

  • Depsipeptides / chemical synthesis*
  • Depsipeptides / chemistry
  • Depsipeptides / pharmacology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Histone Deacetylase Inhibitors*
  • Molecular Structure

Substances

  • Depsipeptides
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • romidepsin