Total syntheses of cis-cyclopropane fatty acids: dihydromalvalic acid, dihydrosterculic acid, lactobacillic acid, and 9,10-methylenehexadecanoic acid

Org Biomol Chem. 2014 Dec 14;12(46):9427-38. doi: 10.1039/c4ob01863j. Epub 2014 Oct 16.


cis-Cyclopropane fatty acids (cis-CFAs) are widespread constituents of the seed oils of subtropical plants, membrane components of bacteria and protozoa, and the fats and phospholipids of animals. We describe a systematic approach to the synthesis of enantiomeric pairs of four cis-CFAs: cis-9,10-methylenehexadecanoic acid, lactobacillic acid, dihydromalvalic acid, and dihydrosterculic acid. The approach commences with Rh2(OAc)4-catalyzed cyclopropenation of 1-octyne and 1-decyne, and hinges on the preparative scale chromatographic resolution of racemic 2-alkylcycloprop-2-ene-1-carboxylic acids using a homochiral Evan's auxiliary. Saturation of the individual diastereomeric N-cycloprop-2-ene-1-carbonylacyloxazolidines, followed by elaboration to alkylcyclopropylmethylsulfones, allowed Julia-Kocienski olefination with various ω-aldehyde-esters. Finally, saponification and diimide reduction afforded the individual cis-CFA enantiomers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes / chemistry
  • Carboxylic Acids / chemistry
  • Catalysis
  • Fatty Acids / chemical synthesis*
  • Oxazoles / chemistry
  • Palmitic Acids / chemical synthesis*
  • Rhodium / chemistry
  • Stereoisomerism


  • Alkynes
  • Carboxylic Acids
  • Fatty Acids
  • Oxazoles
  • Palmitic Acids
  • 9,10-methylenehexadecanoic acid
  • dihydrosterculic acid
  • 1-octyne
  • Rhodium
  • phytomonic acid