Ye Y, Duke C C, Holder G M
Department of Pharmacy, University of Sydney, NSW, Australia.
Chem Res Toxicol. 1995 Mar;8(2):203-8. doi: 10.1021/tx00044a004.
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.
通过反相高效液相色谱法分离了7,9-二甲基苯并[c]吖啶和7,10-二甲基苯并[c]吖啶与未处理的以及经苯巴比妥和3-甲基胆蒽预处理的大鼠肝脏微粒体在孵育过程中形成的单功能化二氢二醇代谢物。通过与(+)-(1R,2S,4S)-内型-1,4,5,6,7,7-六氯双环-[2.2.1]庚-5-烯-2-羧酸（HCA）形成的非对映异构体酯的高效液相色谱法测定每种对映体的相对含量。对于K区域二氢二醇，使用经验方法从其圆二色光谱确定绝对构型。7,9-二甲基苯并[c]吖啶的3,4-二氢二醇的绝对构型通过其双-4-(二甲基氨基)苯甲酸酯的CD光谱的激子手性方法确定。对于7,10-二甲基苯并[c]吖啶的8,9-二氢二醇，通过将(+)-HCA酯与文献数据进行正相高效液相色谱比较，初步确定其绝对构型。在每种情况下，对于非K区域二氢二醇，R,R-构型占主导，光学纯度>86%，对于K区域二氢二醇，光学纯度为56-68%。
