Synthesis and properties of methyl 5-(1′ R,2′ S)-(2-octadecylcycloprop-1-yl)pentanoate and other ω-19 chiral cyclopropane fatty acids and esters related to mycobacterial mycolic acids

• Published in: Chemistry and physics of lipids 2004, Vol.127 (1), p.35-46
• Main Authors: Coxon, Geoffrey D, Al Dulayymi, Juma’a R, Morehouse, Caroline, Brennan, Patrick J, Besra, Gurdyal S, Baird, Mark S, Minnikin, David E
• Format: Article
• Language: English
• Subjects: Biosynthetic inhibitors; Carbon Isotopes - chemistry; Cell Wall - chemistry; Chiral cyclopropane; Chromatography, Thin Layer; Cyclopropanes - chemical synthesis; Cyclopropanes - chemistry; Esters - chemistry; Fatty acids; Fatty Acids - chemical synthesis; Fatty Acids - chemistry; Mycobacterium smegmatis - chemistry; Mycolic acids; Mycolic Acids - chemical synthesis; Mycolic Acids - chemistry; Valerates - chemical synthesis; Valerates - chemistry
• ISSN: 0009-3084; 1873-2941
• DOI: 10.1016/j.chemphyslip.2003.09.001

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 14 C -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.