Total Synthesis of Tetarimycin A, (±)-Naphthacemycin A9, and (±)-Fasamycin A: Structure-Activity Relationship Studies against Drug-Resistant Bacteria

J Org Chem. 2018 Jun 15;83(12):6508-6523. doi: 10.1021/acs.joc.8b00802. Epub 2018 May 30.

Abstract

Making use of a reductive olefin coupling reaction and Michael-Dieckmann condensation as two key operations, we have completed a concise total synthesis of tetarimycin A, (±)-naphthacemycin A9, and (±)-fasamycin A in a highly convergent and practical protocol. Synthetic procedures thus developed have also been applied to provide related analogues for structure-activity relationship studies, thereby coming to the conclusion that the free hydroxyl group at C-10 is essential for exerting inhibitory activities against a panel of Gram-positive bacteria, including drug-resistant strains VRE and MRSA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biphenyl Compounds / chemical synthesis*
  • Biphenyl Compounds / pharmacology*
  • Drug Resistance, Microbial / drug effects*
  • Gram-Positive Bacteria / drug effects*
  • Naphthacenes / chemical synthesis*
  • Naphthacenes / pharmacology*
  • Polycyclic Aromatic Hydrocarbons / chemical synthesis*
  • Polycyclic Aromatic Hydrocarbons / pharmacology*
  • Polycyclic Compounds / chemical synthesis*
  • Polycyclic Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Biphenyl Compounds
  • Naphthacenes
  • Polycyclic Aromatic Hydrocarbons
  • Polycyclic Compounds
  • fasamycin A
  • naphthacemycin A9
  • tetarimycin A