右旋黄皮酰胺在大鼠肝微粒体中的代谢转化

目的：研究黄皮酰胺的主要代谢途径，为进一步研究黄皮酰胺代谢的立体选择性打下基础。方法：用大鼠肝微粒体体外温孵法对右旋黄皮酰胺((+)-clausenamide)进行温孵，用硅胶柱色谱、制备TLC分离纯化代谢产物并通过光谱分析鉴定其结构。结果：分离得到5个代谢产物CM1,CM3,CM4,CM5及CM6,其结构分别鉴定为6-羟基，4-羟基，4，6-二羟基，4-苯环邻位羟基，4，7-苯环间位-二羟基黄皮酰胺。结论：黄皮酰胺的代谢主要发生羟化或双羟化,CM3是其主要代谢产物,量较少的CM4,CM6为其进一步代谢产生的双羟基代谢产物;另2个代谢产物CM1,CM5产生的量也较少；CM2未分离得到，但通过HPLC分析知其为右旋黄皮酰胺的微量代谢产物。

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 NADPHgenerating 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 6hydroxyl, 4hydroxyl, 4,6dihydroxyl, 4phenylorthohydroxyl, 4,7phenylmetodihydroxyl clausenamide by 1HNMR and FABMS. 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.