METABOLIC TRANSFORMATION OF (+)-CLAUSENAMIDE IN RAT LIVER MICROSOMES

AIM: To find the metabolic pathway of (+)-clausenamide in rat liver microsomal incubate and give the basis of studying the stereoselectivity of the metabolism of clansenamide. METHODS: (+)-Clausenamide was incubated in rat liver microsomal incubate containing NADPH-generating system and the metabolites were isolated and purified by using silica gel column and preparative TLC and then their structures were determined by 1HNMR and MS. RESULTS: Five metabolites, CM1, CM3, CM4, CM5 and CM6, were obtained, and their structures were determined as 6-hydroxyl-, 4-hydroxyl-, 4,6-dihydroxyl-, 4-phenyl-ortho-hydroxyl-, 4,7-phenyl-meto-dihydroxyl- clausenamide by ¹HNMR and FAB-MS. CONCLUSION: The metabolism of (+)-clausenamide were hydroxylation or dihydroxylation. CM3 is the main monohydroxyl- metabolite, both CM4 and CM6 are dihydroxoyl- metabolites generated from CM3. The amount of the other two metabolites, CM1 and CM5, is much less. Although CM2 is not isolated from the incubate it is also detected by HPLC.