17S,20S-Methanofusidic acid, a new potent semi-synthetic fusidane antibiotic

Bioorg Med Chem Lett. 2002 Dec 16;12(24):3569-72. doi: 10.1016/s0960-894x(02)00797-7.

Abstract

A novel fusidic acid type antibiotic having the side chain linked to the tetracyclic ring system via a spiro-cyclopropane system is described. 17S,20S-Methanofusidic acid is obtained by an efficient synthetic route including cyclopropanation of the Delta17(20) bond with attack solely from the least hindered alpha-face. The spiro-cyclopropane system orients the side chain into a bioactive conformational space. The new 17S,20S-methanofusidic acid exerts antibacterial activity against several Gram-positive species with potency essentially equal to natural fusidic acid.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Drug Resistance, Bacterial
  • Fusidic Acid / analogs & derivatives*
  • Fusidic Acid / chemical synthesis*
  • Fusidic Acid / pharmacology
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Structure-Activity Relationship

Substances

  • 17,20-methanofusidic acid
  • Anti-Bacterial Agents
  • Fusidic Acid