Free radical oxidation of coriolic acid (13-(S)-hydroxy-9Z,11E-octadecadienoic acid

The reaction of (13S,9Z,11E)-13-hydroxy-9,11-octadecadienoic acid, one of the major peroxidn. products of linoleic acid and an important physiol. mediator, with the Fenton reagent (Fe2+/EDTA/H2O2) was investigated. In phosphate buffer, pH 7.4, the reaction proceeded with >80% substrate consumption after 4 h to give a defined pattern of products, the major of which were isolated as Me esters and were subjected to complete spectral characterization. The less polar product was identified as (9Z,11E)-13-oxo-9,11-octadecadienoate Me ester (40% yield). Based on 2D NMR anal. the other two major products were formulated as (11E)-9,10-epoxy-13-hydroxy-11-octadecenoate Me ester (15% yield) and (10E)-9-hydroxy-13-oxo-10-octadecenoate Me ester (10% yield). Mechanistic expts., including deuterium labeling, were consistent with a free radical oxidn. pathway involving as the primary event H-atom abstraction at C-13, as inferred from loss of the original S configuration in the reaction products. Overall, these results provide the first insight into the products formed by oxidn. of (13S,9Z,11E)-13-hydroxy-9,11-octadecadienoic acid with the Fenton reagent, and hint at novel formation pathways of the hydroxyepoxide and hydroxyketone of potential (patho)physiol. relevance in settings of oxidative stress.