Total synthesis of RNA-polymerase inhibitor ripostatin B and 15-deoxyripostatin A

Angew Chem Int Ed Engl. 2012 Apr 2;51(14):3401-4. doi: 10.1002/anie.201108749. Epub 2012 Feb 29.

Abstract

Keep me skipped: a highly convergent total synthesis of ripostatin B, an inhibitor of the bacterial RNA polymerase, is described. The key steps to construct and avoid isomerization of the skipped triene are a double Stille cross-coupling reaction and a ring-closing metathesis. Furthermore, 15-deoxyripostatin A, a stable and conformationally locked analogue of ripostatin A, was prepared and tested in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • DNA-Directed RNA Polymerases / antagonists & inhibitors*
  • DNA-Directed RNA Polymerases / metabolism
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / drug effects
  • Lactones / chemical synthesis*
  • Lactones / chemistry
  • Lactones / pharmacology
  • Myxococcales / enzymology
  • Staphylococcus aureus / drug effects
  • Stereoisomerism

Substances

  • 15-deoxyripostatin A
  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • Lactones
  • ripostatin B
  • DNA-Directed RNA Polymerases