槲皮苷衍生物的合成及药理作用研究  

Synthesis and Pharmacological Activities of a Quercetin Derivative

作　　者：汤小平 马哲龙[2] 施宁川[2] 丁志山[2] 蒋福升[2] 

机构地区：[1]富阳市妇幼保健院药剂科,浙江富阳311400 [2]浙江中医药大学生命科学院

出　　处：《中国药师》2016年第2期251-254,共4页China Pharmacist

摘　　要：目的：初步探讨槲皮苷衍生物3＇,4＇,5,7-四-（O-甲氧羰甲基）槲皮苷的合成及对心肌缺血的作用。方法：以槲皮苷为原料,N,N-二甲基甲酰胺（DMF）为溶剂,在无水碳酸钾存在下,缓慢滴加氯乙酸甲酯,在3＇、4＇、5、7位引入醚键,预得到目标产物3＇,4＇,5,7-四-（O-甲氧羰甲基）槲皮苷。化合物结构经LC-MS、1H-NMR进行了表征。利用薄膜分散法将产物3＇,4＇,5,7-四-（O-甲氧羰甲基）槲皮苷制成纳米乳,通过腹腔注射给药,观察其对垂体后叶素诱导的心肌缺血大鼠心血管系统的作用。结果：合成了3＇,4＇,5,7-四-（O-甲氧羰甲基）槲皮苷,体外代谢试验证明该产物大部分被代谢为末端游离羧基的去甲基产物,极性明显增大。心电图及动物试验结果显示产物对垂体后叶素致心肌缺血大鼠有一定的抗心肌缺血作用。结论：3＇,4＇,5,7-四-（O-甲氧羰甲基）槲皮苷制成纳米乳腹腔注射对静脉注射垂体后叶素的心肌缺血模型大鼠有明显的对抗作用。Objective： To preliminarily explore the synthesis of a quercetin derivative 3＇,4＇,5,7-four-（ O-methoxy carbonyl meth- yl） quereetin and its pharmacological activities. Methods： Quercetin as the reactant and N,N-dimethyl-formamide （DMF） as the solvent, the target product 3＇,4＇ ,5,7-four-（ O-methoxy earbonyl methyl） quereetin was obtained by the slow addition of methyl chloroacetate in the presence of anhydrous K2CO3 to introduce ether bond at 3＇ ,4＇ ,5,7- bit. The structure was characterized by LC-MS, 1H- NMR and element analysis. The nanoemulsion of the product was prepared using a film dispersion method, and with intraperitoneal injection, the effect on pituitrin-induced myocardial ischemia cardiovascular system in rats was observed. Results： 3＇,4＇ ,5,7-Four- （O- methoxy carbonyl methyl） quercetin was successfully synthesized, and could be metastasized to a demethylation product containing distal free carboxyl with increased polarity proved by metabohc tests in vitro. The results of electrocardiogram and animal experiments showed that the compound had improving effects on pituitrin-induced myocardial ischemia in rats. Conclusion： The nanoemulsion of 3＇ ,4＇ ,5,7-four-（ O-methoxy carbonyl methyl） quercetin with intraperitoneal injection shows significant antagonism against pituitrin-in- duced myocardial ischemia in rats.

关 键 词：槲皮苷 合成 药理作用 

分 类 号：R284.3[医药卫生—中药学] R285.5[医药卫生—中医学]