Racemic and optically active 2-methoxy-4-oxatetradecanoic acids: novel synthetic fatty acids with selective antifungal properties.
The unprecedented (+/-)-2-methoxy-4-oxatetradecanoic acid and the optically pure (S)-2-methoxy-4-oxatetradecanoic acid were synthesized in six steps and in 11-14% overall yields starting with either 1,2-O-isopropylidene-rac-glycerol or 1,2-O-isopropylidene-(S)-glycerol. The key step in the synthesis was the selective monosilylation of a dibutylstannylene intermediate. The title compounds displayed selective fungitoxicity in the range of 0.08-0.22 mM against Cryptococcus neoformans ATCC 66031 and Aspergillus niger ATCC 16404, but no significant activity against C. albicans ATCC 14053 and ATCC 60193 (>2.6 mM). Albeit being good substrates for N-myristoyltransferases (NMTs), the racemic and the S-enantiomer of the oxygenated 2-methoxylated compounds showed no significant difference in antifungal activity. This finding suggests an alternative mechanism of fungitoxicity other than NMT inhibition.
Carballeira
Néstor M
NM
Department of Chemistry, University of Puerto Rico, P.O. Box 23346, San Juan, PR 00931-3346, USA. ncarball@upracd.upr.clu.edu
O'Neill
Rosann
R
Parang
Keykavous
K
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001234:Aspergillus niger / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism
D000935:Antifungal Agents; D005230:Fatty Acids, Nonesterified; C076272:4-oxatetradecanoic acid