The first total synthesis of the (±)-17-methyl- trans-4,5-methyleneoctadecanoic acid and related analogs with antileishmanial activity

Abstract

The first total synthesis of the marine cyclopropane fatty acid (±)-17-methyl- trans-4,5-methyleneoctadecanoic acid was accomplished in eight steps and in 9.1% overall yield starting from 1-bromo-12-methyltridecane. The cis analog (±)-17-methyl- cis-4,5-methyleneoctadecanoic acid was also synthesized but in seven steps and in 16.4% overall yield. With the two isomeric cyclopropane fatty acids at hand it was possible to unequivocally corroborate the trans relative configuration of the naturally occurring fatty acid by gas chromatographic co-elution of the corresponding methyl esters. The cis isomer was cytotoxic to Leishmania donovani promastigotes with an IC 50 of 300.2 ± 4.2 μM.