联苯双酯代谢产物的分离和鉴定

给大鼠灌胃联苯双酯后,用TLC法分离尿中代谢产物。发现尿中的主要代谢物为葡萄糖醛酸结合物,将此结合物水解后,用TLC法分离到一种极性较葡萄糖醛酸结合物为弱的代谢物,经光谱分析测定其结构为4-羟基-4′-甲氧基-5,6,5′,6′-二次甲二氧基-2,2′-二甲氧羰基联苯(简称4-去甲联苯双酯)。此外还证实,大鼠灌胃后在肝、肾组织中均以葡萄糖醛酸结合物为主,仪有少量非结合形代谢物和原形药物。

ISOLATION AND IDENTIFICATION OF THE URINARY METABOLITE OF BIPHENYL DIMETHYL DICARBOXYLATE

Dimethyl-4, 4'-dimethoxy-5, 6, 5', 6'-dimethylenedioxybiphenyl-2, 2'-dicarboxylate(Biphenyl dimethyl dicarboxylate, BDD) is originally an intermediate for the synthesis of schizandrin C analogs. It has been shown to be useful for the treatment of chronic hepatitis.After oral administration of BDD to rats, a water soluble metabolite was separated from urine by TLC. After hydrolysis of the metabolite by incubation with glucuronidase, a compound was isolated by TLC and identified by MS, IR and NMR spectra to be dimethyl-4-hydroxy-4'-methoxy-5, 6, 5', 6'-dimethylenedioxybiphenyl-2, 2'-dicarboxylate(4-demethyl-BDD). The water soluble metabolite in urine is apparently a conjugate of 4-demethyl-BDD with glucuronic acid.After oral administration of ~3H-BDD to rats, the main part of the radioactivity in liver or kidney appears to be the glucuronide of 4-demethyl-BDD.