A 23–26-carbon chain length range of ω-19 (1′R,2′S) cyclopropane fatty acids, related to mycobacterial mycolic acids, has been prepared. The key cyclopropyl intermediate, (1′R,2′S)-(Z)-1-formyl-2-octadecylcyclopropane, underwent Wittig chemistry with various reagents to provide vinylic precursors, which were selectively reduced to the corresponding saturated ω-19 cyclopropane fatty acids or esters. The 24-carbon ω-19 cyclopropane ester was made by chain elongation of the 23-carbon ester. Saturated and unsaturated chiral cyclopropane acids and esters were assayed, using wall extracts of Mycobacterium smegmatis; the incorporation of -acetate was used to measure inhibition or stimulation of mycolic acid synthesis. Minor inhibition (2–3%) was shown by the 23- and 24-carbon saturated esters; all the other compounds were stimulants. The most effective (38–55%) stimulators of mycolate synthesis were the unsaturated esters with 23- and 26-carbons and the saturated and unsaturated 25-carbon acids.
- fatty acids
- biosynthetic inhibitors
- mycolic acids
- chiral cyclopropane
Coxon, G. D., Al Dulayymi, J. R., Morehouse, C., Brennan, P. J., Besra, G. S., Baird, M. S., & Minnikin, D. E. (2004). Synthesis and properties of methyl 5-(1R,2S)-(2-octadecylcycloprop-1-yl)pentanoate and other ω-19 chiral cyclopropane fatty acids and esters related to mycobacterial mycolic acids. Chemistry and Physics of Lipids, 127(1), 35-46. https://doi.org/10.1016/j.chemphyslip.2003.09.001