Synthesis of methyl (Z)-tetracos-5-enoate and both enantiomers of ethyl (E)-6-methyltetracos-4-enoate: possible intermediates in the biosynthesis of mycolic acids in mycobacteria

The high molecular weight 2-alkyl-3-hydroxy mycolic acids are key structural components of the cell envelope of pathogenic mycobacteria, such as Mycobacterium tuberculosis. A prime target for drug action would be the initial stages where the biosynthetic pathways diverge from those of ordinary fatty acids. It has been postulated that the pathway for the α-mycolates, without oxygen functions in addition to the hydroxy-acid unit, appears to diverge from (Z)-tetracos-5-enoic acid. The biosynthesis of oxygenated mycolic acids is considered to possibly diverge from (E)-6-(R)-methyltetracos-4-enoic and (E)-6-(S)-methyltetracos-4-enoic acids. This communication describes the synthesis of esters of these acids in order to test their potential role in the biosynthesis of mycolic acids.