Ph. Buist et al., SYNTHESIS AND DESATURATION OF MONOFLUORINATED FATTY-ACIDS, Journal of the Chemical Society. Perkin transactions. I, (17), 1997, pp. 2617-2624
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.