Armeniaspiroles, a new class of antibacterials: Antibacterial activities and total synthesis of 5-chloro-Armeniaspirole A

Bioorg Med Chem Lett. 2012 Oct 1;22(19):6292-6. doi: 10.1016/j.bmcl.2012.06.107. Epub 2012 Jul 9.

Abstract

Armeniaspiroles, a novel class of natural products isolated from Streptomyces armeniacus, are characterized by a novel spiro[4.4]non-8-ene scaffold. Various derivatives of Armeniaspiroles could be obtained by halogenation, alkylation, addition/elimination or reductions. A total synthesis of the 5-chloro analog of Armeniaspirole A has been accomplished in a linear six-step sequence. 5-Chloro-Armeniaspirole A exhibits good activity against a range of multidrug-resistant, Gram-positive bacterial pathogens.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / isolation & purification
  • Anti-Bacterial Agents / pharmacology*
  • Biological Products / chemical synthesis
  • Biological Products / chemistry
  • Biological Products / isolation & purification
  • Biological Products / pharmacology
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • ERG1 Potassium Channel
  • Enterococcus faecium / drug effects
  • Enterococcus faecium / growth & development
  • Ether-A-Go-Go Potassium Channels / antagonists & inhibitors
  • Humans
  • Lactams / chemistry
  • Lactams / isolation & purification
  • Lactams / pharmacology*
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Methicillin-Resistant Staphylococcus aureus / growth & development
  • Mice
  • Molecular Structure
  • Spiro Compounds / chemistry
  • Spiro Compounds / isolation & purification
  • Spiro Compounds / pharmacology*
  • Streptococcus pneumoniae / drug effects
  • Streptococcus pneumoniae / growth & development
  • Structure-Activity Relationship

Substances

  • 5-chloro-armeniaspirole A
  • Anti-Bacterial Agents
  • Biological Products
  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Lactams
  • Spiro Compounds