Studies On The Biotransformation And Its Stereoselectivity Of Chiral Clausenamide

Clausenamide is a chiral nootrotic drug extracted from Clausena lansium(Lour.) Skeels. Its preclinical research is just in doing. The nootrotic effect of (-)-clausenamide is much better than that of (+)-clausenamide and the latter has stronger toxicity than the former.The biotransformations of (+) and (-)-clausenmide have been investigated in vitro and in vivo and the differences between the biotransformations of (+) and (-)-clausenamide have been found. The research was mainly concerned with the following subjects:1. The optimization of the constitutions of microsomal incubate system and the development of the HPLC method for the analysis of clausenamide and its metabolites.The best microsomal incubate system was optimized by the NADPH-generatingsystem. The RP-HPLC—DAD method for the analysis of clausenamide and itsmetabolites has been investigated Ten metabolites of clausenamide have beendetected from the microsomal incubate and the differences of the biotransformations between (+) and (-)-clausenamide were found. 2. The isolation and structure elucidation of the metabolites and the proposition of the metabolic pathway of clausenamide.500ml of incubate systems of (+) and (-)-clausenmide were prepared and the clausenamide and its metabolites were extracted with EtOAc. Six metabolites were isolated and purified by silica gel column and preparative TLC. Two of them (CM1 and CM2) were from incubate system of (-)-clausenamide and four(CM3, CM4,...