Synthesis and properties of methyl 5-(1'R,2'S)-(2-octadecylcycloprop-1-yl)pentanoate and other omega-19 chiral cyclopropane fatty acids and esters related to mycobacterial mycolic acids.
A 23-26-carbon chain length range of omega-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 omega-19 cyclopropane fatty acids or esters. The 24-carbon omega-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 14C-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.
Coxon
Geoffrey D
GD
Department of Chemistry, University of Newcastle, Newcastle upon Tyne NE1 7RU, UK.
Al Dulayymi
Juma'a R
JR
Morehouse
Caroline
C
Brennan
Patrick J
PJ
Besra
Gurdyal S
GS
Baird
Mark S
MS
Minnikin
David E
DE
D002247:Carbon Isotopes / Q000737:chemistry; D002473:Cell Wall / Q000737:chemistry; D002855:Chromatography, Thin Layer; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry; D004952:Esters / Q000737:chemistry; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000737:chemistry; D020102:Mycobacterium smegmatis / Q000737:chemistry*; D009171:Mycolic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D014631:Valerates / Q000138:chemical synthesis* / Q000737:chemistry
D002247:Carbon Isotopes; D003521:Cyclopropanes; D004952:Esters; D005227:Fatty Acids; D009171:Mycolic Acids; D014631:Valerates; C028775:cyclopropane fatty acids; C490812:methyl 5-(1'R,2'S)-(2-octadecylcycloprop-1-yl)pentanoate