川芎嗪代谢物糖酯衍生物的合成及生物活性  

Synthesis and bioactivity of glycosyl ester derivatives of the metabolism of tetramethylpyrazine

作　　者：王颖 李蕾 王兴达 李颖晨 韩泳平 

机构地区：[1]西南民族大学药学院,四川成都610041

出　　处：《化学研究与应用》2018年第1期41-45,共5页Chemical Research and Application

基　　金：国家十二五科技支撑计划项目(2012BAI27B07)资助;西南民族大学研究生创新项目(CX2017SZ083)资助

摘　　要：针对川芎嗪在体内易代谢、作用时间过短等问题,通过KMnO_4氧化川芎嗪法制备了其活性代谢物3,5,6-三甲基吡嗪甲酸,并与5种溴代糖缩合合成了不同的糖酯,有关中间体和目标化合物的结构均经过IR、~1HNMR和MS确证;在此基础上考察了5种糖酯衍生物的抗凝血和抗急性缺氧活性,结果表明,给药1h后川芎嗪和糖酯衍生物抗凝血和抗急性缺氧效果差距不大,但给药3h后的糖酯衍生物仍有较好的抗凝血和抗急性缺氧活性能力,这也表明新合成的几种川芎嗪糖酯类衍生物有效地减缓了川芎嗪在体内的代谢速度、延长了体内作用时间。To the question of easy metabolism in vivo and short effect time of ligustrazine, the active metabolite 3,5,6- trimeth- ylpyrazine formic acid was prepared by the method of oxidizing Ligustrazine by KMn〇 4 , and its glycosyl ester derivatives were syn-thesized by condensation of 3 ,5 , 6-trimethylpyrazine formic acid with 5 kinds of brominated sugar. The structures of the intermedi-ates and the target compounds were identifided by IR,1HNMR and MS. The activity of anticoagulant and anti-acute hypoxia for the five glycosyl ester derivatives were investigated. The result showed that the gap of effect of anticoagulant and anti-acute hypoxia of l i-gustrazine and its glycosyl ester derivatives was small in 1h,but after 3h,the activities of glycosyl esters derivatives were still better than ligustrazine,which also showed that the new glycolipid derivatives of ligustrazine were effective in slowing the metabolism and prolonging the time of action in vivo.

关 键 词：川芎嗪 3 5 6-三甲基吡嗪甲酸 糖酯化 生物活性 

分 类 号：O629.11[理学—有机化学]