Myoglobin-Catalyzed bis-Allylic Hydroxylation and Epoxidation of Linoleic Acid

Abstract

Linoleic acid was treated with metmyoglobin and cumene hydroperoxide at 0°C under anaerobic conditions. Five major compounds were identified, i.e., 11-hydroxylinoleic acid (29% yield),cis-9,10-epoxy-(12Z)-octadecenoic acid (16%),cis-12,13-epoxy-(9Z)-octadecenoic acid (8%), 9-hydroxy-(10E,12Z)-octadecadienoic acid (4%), and 13-hydroxy-(9Z,11E)-octadecadienoic acid (4%). Steric analysis showed that these compounds were all racemic. The steric course of the formation of the major metabolite, (11R,S)-hydroxylinoleic acid, was studied by incubation of linoleic acids stereospecifically deuterated at C-11. It was found that the (11R)-hydroxylinoleic acid lost most of the deuterium label when formed from [(11R)-2H]linoleic acid but retained the label when formed from [(11S)-2H]linoleic acid. Furthermore, the (11S)-hydroxylinoleic acid retained and lost most of the label when produced from [(11R)-2H]- and [(11S)-2H]linoleic acids, respectively. Thus, although the myoglobin-promoted hydroxylation of linoleic acid into 11-hydroxylinoleic acid lacked apparent stereospecificity and produced equal amounts of theRandSenantiomers, the course of the reaction was stereospecific and involved hydrogen abstraction and oxygen insertion occurring with retention of absolute configuration of the carbon atom hydroxylated.