Synthesis of methyl 3-(2-octadecylcyclopropen-1-yl)propanoate and methyl 3-(2-octadecylcyclopropen-1-yl)pentanoate and cyclopropane fatty acids as possible inhibitors of mycolic acid biosynthesis

Article abstract of DOI:10.1016/0009-3084(94)02315-8

(Z)-Tetracos-5-enoic acid is a key intermediate in the biosynthesis of mycobacterial mycolic acids. Recently the methyl ester of its cyclopropene analogue, methyl 4-(2-octadecylcyclopropen-1-yl)butanoate, was shown to act as an inhibitor of mycolic acid biosynthesis. The related analogues methyl 5-(2-octadecylcyclopropen-1-yl)pentanoate and methyl 3-(2-octadecylcyclopropen-1-yl)propanoate have been synthesised, as well as the related cyclopropane esters methyl (Z)-4-(2-octadecylcyclopropan-1-yl)butanoate and methyl (Z)-5-(2-octadecylcyclopropan-1-yl)pentanoate. The synthesis of methyl 3-(2-octadecylcyclopropen-1-yl)propanoate involved protection of the cyclopropene ring by iodination to allow oxidation of an alcohol to a carboxylic acid; the diiodocyclopropane was deprotected by a new mild procedure using activated zinc.