Myoglobin-catalyzed bis-allylic hydroxylation and epoxidation of linoleic acid.
Linoleic acid was treated with metmyoglobin and cumene hydroperoxide at 0 degrees 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 the R and S enantiomers, 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.
Hamberg
M
M
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. Mats.Hamberg@mbb.ki.se
D001555:Benzene Derivatives / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003903:Deuterium / Q000378:metabolism; D004852:Epoxy Compounds / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism; D006900:Hydroxylation; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D008041:Linoleic Acids / Q000737:chemistry / Q000378:metabolism*; D008786:Metmyoglobin / Q000737:chemistry*; D015394:Molecular Structure; D010100:Oxygen / Q000378:metabolism; D013229:Stearic Acids / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism
D001555:Benzene Derivatives; D004852:Epoxy Compounds; D005609:Free Radicals; D008041:Linoleic Acids; D013229:Stearic Acids; D008786:Metmyoglobin; D006859:Hydrogen; D003903:Deuterium; D007501:Iron; C007164:cumene hydroperoxide; D010100:Oxygen