TY - JOUR
T1 - Synthesis and properties of methyl 5-(I'R, 2'S)-(2-octadecylcyloprop-1-yl) pentaboate and other w-19 chiral cyclopropane fatty acids and esters related to mycobacterail mycolic acids
AU - Coxon, GDE
AU - Al Dulayymi, JR
AU - Morhouse, C
AU - Brennan, PJ
AU - Besra, Gurdyal
AU - Baird, MS
AU - Minnikin, David
PY - 2004/1/1
Y1 - 2004/1/1
N2 - 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 C-14-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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
AB - 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 C-14-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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
KW - fatty acids
KW - mycolic acids
KW - chiral cyclopropane
KW - biosynthetic inhibitors
UR - http://www.scopus.com/inward/record.url?scp=0345791445&partnerID=8YFLogxK
U2 - 10.1016/j.chemphyslip.2003.09.001
DO - 10.1016/j.chemphyslip.2003.09.001
M3 - Article
C2 - 14706739
SN - 0009-3084
VL - 127
SP - 35
EP - 46
JO - Chemistry and Physics of Lipids
JF - Chemistry and Physics of Lipids
ER -