Mechanism of linoleic acid hydroperoxide reaction with alkali

Treatment of (13S,9Z,11E)-13-hydroperoxy-9,11-octadecadienoic acid (13S-HPODE) with strong alkali resulted in the formation of about 75% of the corresponding hydroxy acid, (13S,9Z,11E)-13-hydroxy-9,11-octadecadienoic acid (13S-HODE), and the remaining 25% of products was a mixture of several oxidized fatty acids, the majority of which was formed from (9Z,11R,S,12S,R)-13-oxo-11,12-epoxy-9-octadecenoic acid by Favorskii rearrangement (Gardner, H.W., et al. (1993) Lipids 28, 487-495). In the present work, isotope experiments were completed in order to get further information about the initial steps of the alkali-promoted decomposition of 13S-HPODE. 1. Reaction of [hydroperoxy-O-18(2)]13S-HPODE with 5 M KOH resulted in the formation of [hydroxy-O-18]13S-HODE and [epoxy-O-18](9Z,11R,S,12S,R)-13-oxo-11,12-epoxy-9-octadecenoic acid; 2. treatment of a mixture of [U-C-14]13S-HODE and [hydroperoxy-O-18(2)]13S-HPODE with KOH and analysis of the reaction product by radio-TLC showed that 13S-HODE was stable under the reaction conditions and did not serve as precursor of other products; 3. reaction of a mixture of [U-C-14]13-oxo-9,11-octadecadienoic acid (13-OODE) and [hydroperoxy-O-18(2)]13S-HPODE with KOH resulted in the formation of [U-C-14-epoxy-O-18] (9Z,11R,S,12S,R)-13-oxo-11,12-epoxy-9-octadecenoic acid; 4. treatment of a mixture of [hydroperoxy-O-18(2)]13S-HPODE and [carboxyl-O-18(1)]13S-HPODE with KOH afforded (9Z,11R,S,12S,R)-13-oxo-11,12-epoxy-9-octadecenoic acid having an O-18-labeling pattern which was in agreement with its formation by intermolecular epoxidation. It was concluded that (9Z,11R,S,12S,R)-13-oxo-11,12-epoxy-9-octadecenoic acid is formed from 13S-HPODE by a sequence involving initial dehydration into the alpha,beta-unsaturated ketone, 13-OODE, followed by epoxidation of the Delta(11) double bond of this compound by the peroxyl anion of a second molecule of 13S-HPODE. Rapid conversion of hydroperoxides by alkali appeared to require the presence of an alpha,beta-unsaturated ketone intermediate as an oxygen acceptor. This was supported by experiments with a saturated hydroperoxide, methyl 12-hydroperoxyoctadecanoate, which was found to be much more resistant to alkali-promoted conversion than 13S-HPODE.