Synthesis and properties of methyl 5-(1'R,2'S)-(2-octadecylcycloprop-1-yl)pentanoate and other omega-19 chiral cyclopropane fatty acids and esters related to mycobacterial mycolic acids

Chem Phys Lipids. 2004 Jan;127(1):35-46. doi: 10.1016/j.chemphyslip.2003.09.001.

Abstract

A 23-26-carbon chain length range of omega-19 (1'R,2'S) cyclopropane fatty acids, related to mycobacterial mycolic acids, has been prepared. The key cyclopropyl intermediate, (1'R,2'S)-(Z)-1-formyl-2-octadecylcyclopropane, underwent Wittig chemistry with various reagents to provide vinylic precursors, which were selectively reduced to the corresponding saturated omega-19 cyclopropane fatty acids or esters. The 24-carbon omega-19 cyclopropane ester was made by chain elongation of the 23-carbon ester. Saturated and unsaturated chiral cyclopropane acids and esters were assayed, using wall extracts of Mycobacterium smegmatis; the incorporation of 14C-acetate was used to measure inhibition or stimulation of mycolic acid synthesis. Minor inhibition (2-3%) was shown by the 23- and 24-carbon saturated esters; all the other compounds were stimulants. The most effective (38-55%) stimulators of mycolate synthesis were the unsaturated esters with 23- and 26-carbons and the saturated and unsaturated 25-carbon acids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carbon Isotopes / chemistry
  • Cell Wall / chemistry
  • Chromatography, Thin Layer
  • Cyclopropanes / chemical synthesis*
  • Cyclopropanes / chemistry
  • Esters / chemistry
  • Fatty Acids / chemical synthesis*
  • Fatty Acids / chemistry
  • Mycobacterium smegmatis / chemistry*
  • Mycolic Acids / chemical synthesis*
  • Mycolic Acids / chemistry
  • Valerates / chemical synthesis*
  • Valerates / chemistry

Substances

  • Carbon Isotopes
  • Cyclopropanes
  • Esters
  • Fatty Acids
  • Mycolic Acids
  • Valerates
  • cyclopropane fatty acids
  • methyl 5-(1'R,2'S)-(2-octadecylcycloprop-1-yl)pentanoate