The epoxyallylic radical from homolysis and rearrangement of methyl linoleate hydroperoxide combines with the thiyl radical of N-acetylcysteine

Abstract

In the absence of O 2, ferric chloride catalyzed a reaction between methyl (13-S)-(9Z,11E)-13-hydroperoxy-9, 11-octadecadienoate and N- acetyl- l- cysteine . Anhydrous tetrahydrofuran was utilized as the solvent to trap products that would be potentially unstable to protic solvents. After methyl esterification with CH 2N 2, four major products were isolated. The isolates were found to be two pairs of epimers; one pair, ( Z)-(12 R,13 S)-11-[[(2 R)-2-acetamido-2-carboxyethyl]thio]-12,13-epoxy-9-octadecenoic acid (dimethyl ester), was epimeric at C-11, and the other, ( E)-(12 S, 13 S)-9-[[(2β)-2-acetamido-2-carboxyethyl]thio]-12,13-epoxy-10-octadecenoic acid (dimethyl ester), differed by the stereoconfiguration at C-9. The latter pair of isomers contained an allylic epoxide; thus, protic solvents promoted ready solvolysis of the epoxide provided that a mild catalyst, such as N-acetylcysteine, was present. Because the epoxide was allylic, substitution was predicted on either side of the intermediate allylic cation (C-10 or C-12), but instead, substitution occurred only at C-10, possibly owing to anchimeric assistance by the thio ether located at C-9. Thus, substitution by methanol led to formation of isomeric 9-[(2-acetamido-2-carboxyethyl)thio]-13-hydroxy-10-methoxy-1]-octadecenoic acid, dimethyl ester. This combination reaction of fatty ester hydroperoxide with 7V-acetylcysteine may explain the sensitivity of sulfhydryl proteins to lipid peroxidation.