小檗碱C(9)位硫辛酸酯类化合物的合成及量子化学计算研究

Design Synthesis and Quantum Chemical Calculations of C(9)Lipoic Acid Esters of Berberine

现代医学研究证实,小檗碱具有显著的降糖活性和临床安全性。目前,临床应用的降糖药物能够有效控制血糖,但使用不方便,副作用的问题难以避免,且对胰岛素分泌不足、胰岛素抵抗等问题研究少之甚少。本文以小檗碱为先导化合物,对其C(9)位进行结构修饰,并在相应的位点引入具有抗氧化作用的硫辛酸,合成了小檗碱C(9)位硫辛酸酯及其类似物,希望能够得到一种具有双功能双位点的新型降糖药物,达到修复和改善胰岛功能的目的。中间体9-O-取代基类BBR的合成是反应中关键一步,通过量子化学计算比较了三种试剂1,2-二溴乙烷、2-溴乙醇、环氧乙烷的亲电反应能力,为后续中间体的合成工艺提供初步理论依据。

Modern medical research has confirmed that berberine has significant glucose lowering activity and clinical safety.At present,clinically used hypoglycemic drugs can effectively control blood glucose,but they are inconvenient to use and difficult to avoid the problem of side effects.There are few studies on the problems of insufficient insulin secretion and insulin resistance.In this paper,berberine is used as the lead compound,and lipoic acid with antioxidant effect is introduced into its C(9)position to synthesize lipoic acid berberine ester and its analogues,with the hope of synthesizing a novel glucose lowering drug with dual functional and dual sites to achieve the purpose of repairing and improving the function of pancreatic islets.The synthesis of intermediate 9-O-substituent BBR is a key step in the reaction.Quantum chemical calculations are used to compare the electrophilic reactivity of the three reagents 1,2-dibromoethane,2-bromoethanol,and ethylene oxide.The results of this article can provide a preliminary theoretical basis for the subsequent synthesis of intermediates.