Total synthesis of (+)-chaetocin and its analogues: their histone methyltransferase G9a inhibitory activity

J Am Chem Soc. 2010 Mar 31;132(12):4078-9. doi: 10.1021/ja101280p.

Abstract

The first total synthesis of (+)-chaetocin has been accomplished in nine steps starting from known N-Cbz-N-Me-serine using radical alpha-bromination reaction of diketopiperazine 10 and Co(I)-mediated reductive dimerization reaction of 12 as key reactions. The enantiomers show comparable inhibitory activity toward histone methyltransferase (HMT) G9a, but analogues without the sulfur functionality are inactive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase / antagonists & inhibitors*
  • Humans
  • Molecular Structure
  • Piperazines / chemical synthesis
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Piperazines
  • chaetocin
  • Histone Methyltransferases
  • Histone-Lysine N-Methyltransferase