SYNTHESIS AND DESATURATION OF MONOFLUORINATED FATTY-ACIDS

A series of monofluoro C-16 and C-18 fatty acids have been synthesized and used as mechanistic probes for fatty acid desaturation, Only fluo roolefinic products are obtained when these compounds are processed by an in vivo Saccharomyces cerevisiae Delta(9) desaturating system as d etermined by LH-decoupled F-19 NMR and GC-MS analysis, No evidence for fluorohydrin formation has been found when either methyl (R,S)-9- or 10-fluoropalmitate (stearate) 3a,b and 5a,b was incubated with the Del ta(9) desaturase. On desaturation alpha- and beta-fluorine substituent effects (k(H)/k(F)) of magnitude 6.2 and 2.4, respectively, have been measured by direct competition experiments between 3a and 3b and betw een methyl 16-fluoropalmitate 3c and 3b, These results do not support the involvement of discrete hydroxylated and carbocationic intermediat es in fatty acid desaturation. Substantial apparent steric effects hav e been observed for monofluorostearoyl substrates 5c-f bearing a fluor ine distal from the site of initial oxidation, In the case of (R,S)-me thyl 12-fluorostearate 5f, we show that both enantiomers are desaturat ed at comparable rates.