An improved synthesis of methyl-labeled fatty acids

Abstract

For ongoing studies of lipid-apoprotein interactions in this laboratory, a homologous series of fatty acids labeled at the methyl terminus were requried as precursors for the corresponding labeled phospholipids. Our synthetic scheme for these methyl labeled fatty acids utilized the corresponding methyl keto esters which, upon reduction and hydrolysis, would give the desired acid. In one report (1) of the synthesis of methyl keto esters, dimethyl cadmium was coupled to the half acyl halide of a dicarboxylic acid mono ester to give the desired keto ester. Using this procedure, we obtained low yields of methyl keto ester and many side products. The obvious disadvantages of this procedure in isotopic label ing are: 1) the requirement for excess labeled methyl iodide, 2) loss of the volatile as well as hazardous dimethyl cadmium during the removal of ether which is replaced with benzene, and 3) low yields of methyl keto ester. We, therefore, investigated the use of methyl cadmium chloride and found that it gives high yields of methyl keto esters as illustrated in the scheme below for the synthesis of tetradecanoic-1413C acid (* indicates 13C label).