The absolute stereochemistry of the major trans-dihydrodiol enantiomers formed from 11-methylbenz[a]anthracene by rat liver microsomes.
Circular dichroism (CD) spectra were determined for the trans-3,4-, 5,6-, 8,9-, and 10,11-dihydrodiols which were formed by incubation of the weakly carcinogenic 11-methylbenz[a]anthracene (11-methyl-BA) with liver microsomes from phenobarbital-pretreated, immature males rats of the Sprague-Dawley strain. These CD spectra were compared with those of the corresponding benz[a]anthracene (BA) trans-dihydrodiol enantiomers of known absolute stereochemistry. The trans-dihydrodiol metabolites of BA and 11-methyl-BA were purified from metabolite mixtures by normal-phase and reversed-phase high-performance liquid chromatography (HPLC). The optically pure (-),-BA(3R,4R)-dihydrodiol and (+)-BA(3S,4S)-dihydrodiol were resolved via their diastereomeric di(-)menthoxyacetates by normal-phase HPLC. The CD spectra of the metabolically formed trans-3,4-, 5,6-, 8,9-, and 10,11-dihydrodiols of 11-methyl-BA were found to be closely similar to those of BA(-)-(3R,4R)-, (+)-(5R,6R)-, (-)-(8R,9R)-, and (-)-10R,11R)-dihydrodiols. The results suggest that all the major trans-dihydrodiol enantiomers formed by rat liver microsomes from 11-methyl-BA have R,R absolute configurations.
D000818:Animals; D001551:Benz(a)Anthracenes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D066298:In Vitro Techniques; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D013237:Stereoisomerism
D001551:Benz(a)Anthracenes; C034041:11-methylbenzanthracene