The stereochemistry of the major rat hepatic microsomal metabolites of 7,9-dimethylbenz[c]acridine and 7,10-dimethylbenz[c]acridine.
The monofunctionalized dihydrodiol metabolites of 7,9-dimethylbenz[c]acridine and 7,10-dimethylbenz[c]acridine formed in incubations with rat liver microsomes from untreated and phenobarbital and 3-methylcholanthrene-pretreated rats were isolated by reversed-phase high performance liquid chromatography. The relative amounts of each enantiomer were determined by HPLC of diastereoisomeric esters with (+)-(1R,2S,4S)-endo-1,4,5,6,7,7-hexachlorobicyclo-[2.2.1]hept-5 e ne-2- carboxylic acid (HCA). For the K-region dihydrodiols, absolute configurations were determined from their circular dichroic spectra using the empirical method. The absolute configuration of 3,4-dihydrodiol of 7,9-dimethylbenz[c]acridine was determined by the exciton chirality method from the CD spectrum of its bis-4-(dimethylamino)benzoate ester. For the 8,9-dihydrodiol of 7,10-dimethylbenz[c]acridine the absolute configurations were tentatively assigned by normal-phase HPLC comparison of the (+)-HCA esters with literature data. In every case the R,R-configuration predominated with optical purities > 86% for non-K-region dihydrodiols and 56-68% for the K-region dihydrodiols.
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Department of Pharmacy, University of Sydney, NSW, Australia.
Duke
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D000166:Acridines / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D002942:Circular Dichroism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008968:Molecular Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D000166:Acridines; D002273:Carcinogens; C010123:7,10-dimethylbenz(c)acridine; C031753:7,9-dimethylbenz(c)acridine