Synthesis and Biological Evaluation of a Valinomycin Analog Bearing a Pentafluorophenyl Active Ester Moiety

J Org Chem. 2015 Dec 18;80(24):12646-50. doi: 10.1021/acs.joc.5b02219. Epub 2015 Nov 23.

Abstract

A valuable analog of the K(+)-ionophore valinomycin (1), bearing a pentafluorophenyl ester moiety, has been obtained by selective reaction between the tertiary hydroxyl moiety of analog 2 (available from valinomycin hydroxylation) and the isocyanate group of pentafluorophenyl N-carbonyl glycinate (3) catalyzed by bis(N,N-dimethylformamide)dichlorodioxomolybdenum(VI). LC-HRMS studies show that analog 4 undergoes easy derivatization under mild conditions by reaction with OH- and NH2-containing compounds. Mitochondrial depolarization assays suggest that 4 acts as a K(+)-ionophore, provided that the glycine carboxyl group is appropriately masked.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Esters
  • Glycine / analogs & derivatives
  • Glycine / chemistry
  • Hydrocarbons, Fluorinated / chemistry*
  • Ionophores / chemistry
  • Molecular Structure
  • Potassium / chemistry
  • Valinomycin / chemical synthesis*
  • Valinomycin / chemistry

Substances

  • Esters
  • Hydrocarbons, Fluorinated
  • Ionophores
  • pentafluorophenyl N-carbonyl glycinate
  • Valinomycin
  • Potassium
  • Glycine