Total synthesis of FR901464, an antitumor agent that regulates the transcription of oncogenes and tumor suppressor genes

J Am Chem Soc. 2006 Mar 8;128(9):2792-3. doi: 10.1021/ja058216u.

Abstract

FR901464 is a potent anticancer agent that regulates the transcription of oncogenes and tumor suppressor genes. A convergent enantioselective synthesis of FR901464 was accomplished in 13 linear steps. Central to the synthetic approach was the diene-ene cross olefin metathesis reaction to generate the C6-C7 olefin, without the use of protecting groups, as the final coupling. Additional key reactions include a Zr/Ag-promoted alkynylation to set the C4 stereocenter, a mild and chemoselective Red-Al reduction, a stereoselective Mislow-Evans-type [2,3]-sigmatropic rearrangement to install the C5 stereocenter, a Carreira asymmetric alkynylation to generate the C4' stereocenter, and a highly efficient ring-closing metathesis-allylic oxidation sequence to form an unsaturated lactone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Antineoplastic Agents / chemical synthesis
  • Pyrans / chemical synthesis
  • Silver / chemistry
  • Spiro Compounds / chemical synthesis
  • Threonine / analogs & derivatives
  • Threonine / chemical synthesis
  • Zirconium / chemistry

Substances

  • Alkynes
  • Antineoplastic Agents
  • FR 901464
  • Pyrans
  • Spiro Compounds
  • Threonine
  • Silver
  • Zirconium