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]a cridine and 7,10-dimethylbenz[c]acridine formed in incubations with ra t liver microsomes from untreated and phenobarbital and 3-methylcholan threne-pretreated rats were isolated by reversed-phase high performanc e Liquid chromatography. The relative amounts of each enantiomer were determined by HPLC of diastereoisomeric esters with 7,7-hexachlorobicy clo[2.2.1]hept-5ene-2-carboxylic acid (HCA). For the K-region dihydrod iols, absolute configurations were determined from their circular dich roic 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-(dimethylam ino)benzoate ester. For the 8,9-dihydrodiol of 7,10-dimethylbenz[c]acr idine the absolute configurations were tentatively assigned by normal- phase HPLC comparison of the (+)-HCA esters with literature data. In e very case the R,R-configuration predominated with optical purities >86 % for non-K-region dihydrodiols and 56-68% for the K-region dihydrodio ls.