First total synthesis and antiprotozoal activity of (Z)-17-methyl-13-octadecenoic acid, a new marine fatty acid from the sponge Polymastia penicillus

Chem Phys Lipids. 2009 Sep;161(1):38-43. doi: 10.1016/j.chemphyslip.2009.06.140. Epub 2009 Jun 13.

Abstract

The first total synthesis for the (Z)-17-methyl-13-octadecenoic acid was accomplished in seven steps and in a 45% overall yield. The use of (trimethylsilyl)acetylene was key in the synthesis. Based on a previous developed strategy in our laboratory the best synthetic route towards the title compound was first acetylide coupling of (trimethylsilyl)acetylene to the long-chain protected 12-bromo-1-dodecanol followed by a second acetylide coupling to the short-chain 3-methyl-1-bromobutane, which resulted in higher yields. Complete spectral data is also presented for the first time for this recently discovered fatty acid. The title compound displayed antiprotozoal activity against Leishmania donovani (EC(50) = 19.8 microg/ml) and inhibited the leishmania DNA topoisomerase IB at concentrations of 50 microM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry*
  • Antiprotozoal Agents / pharmacology*
  • DNA Topoisomerases, Type I / metabolism
  • Leishmania donovani / drug effects*
  • Leishmania donovani / enzymology
  • Oleic Acids / chemical synthesis
  • Oleic Acids / chemistry*
  • Oleic Acids / pharmacology*
  • Porifera / chemistry*

Substances

  • Antiprotozoal Agents
  • Oleic Acids
  • 13-octadecenoic acid
  • DNA Topoisomerases, Type I