Study on retroaldol degradation products of antibiotic oligomycin A

J Antibiot (Tokyo). 2014 Feb;67(2):153-8. doi: 10.1038/ja.2013.92. Epub 2013 Oct 2.

Abstract

Studies of reactivity of antibiotic oligomycin A in various alkaline conditions showed that the compound easily undergoes retroaldol degradation in β-hydroxy ketone fragments positioned in the C7-C13 moiety of the antibiotic molecule. Depending on reaction conditions, the retroaldol fragmentation of the 8,9 or 12,13 bonds or formation of a product through double retroaldol degradation, when the fragment C9-C12 was detached, took place followed by further transformations of the intermediate aldehydes formed. The structures of the obtained non-cyclic derivatives of oligomycin A were supported by NMR and MS methods. NMR parameters demonstrate the striking similarity of the geometry (conformation) of the fragment C20-C34 in the non-cyclic products of retroaldol degradation and the starting antibiotic 1. The compounds obtained had lower cytototoxic properties than oligomycin A for human leukemia cells K-562 and colon cancer cells HCT-116 and lower activity against growth inhibition of model object Streptomyces fradiae. It cannot be excluded that the products of retroaldol degradation participate in the biological effects of antibiotic oligomycin A.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Cell Line, Tumor
  • HCT116 Cells
  • Humans
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Oligomycins / chemistry*
  • Oligomycins / pharmacology*
  • Streptomyces / drug effects*

Substances

  • Anti-Bacterial Agents
  • Oligomycins
  • oligomycin A