Synthesis of methyl 3-(2-octadecylcyclopropen-1-yl)propanoate and methyl 3-(2-octadecylcyclopropen-1-yl)pentanoate and cyclopropane fatty acids as possible inhibitors of mycolic acid biosynthesis.
(Z)-Tetracos-5-enoic acid is a key intermediate in the biosynthesis of myocobacterial mycolic acids. Recently the methyl ester of its cyclopropene analogue, methyl 4-(2-octadecylcyclopropen-1- yl)butanoate, was shown to act as an inhibitor of mycolic acid biosynthesis. The related analogues methyl 5-(2-octadecylcyclopropen-1-yl)pentanoate and methyl 3-(2-octadecylcyclopropen-1-yl)propanoate have been synthesized, as well as the related cyclopropane esters methyl (Z)-4-(2-octadecylcyclopropan-1-yl)butanoate and methyl (Z)-5-(2-octadecylcyclopropan-1-yl)pentanoate. The synthesis of methyl 3-(2-octadecylcyclopropen-1-yl)propanoate involved protection of the cyclopropene ring by iodination to allow oxidation of an alcohol to a carboxylic acid; the diiodocyclopropane was deprotected by a new mild procedure using activated zinc.
Hartmann
S
S
Department of Chemistry, University of Newcastle, Newcastle upon Tyne, UK.
Minnikin
D E
DE
Römming
H J
HJ
Baird
M S
MS
Ratledge
C
C
Wheeler
P R
PR
D003517:Cyclopentanes; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects / Q000378:metabolism; D009171:Mycolic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014631:Valerates / Q000737:chemistry* / Q000494:pharmacology
D003517:Cyclopentanes; D003521:Cyclopropanes; D005230:Fatty Acids, Nonesterified; D007202:Indicators and Reagents; D009171:Mycolic Acids; D011422:Propionates; D014631:Valerates; C088517:methyl 3-(2-octadecylcyclopropen--1-yl)pentanoate; C088516:methyl 3-(2-octadecylcyclopropen-1-yl)propanoate