【作者】 贺兴隆；

【导师】 赵龙铉；

【作者基本信息】 辽宁师范大学 ， 有机化学， 2011， 硕士

【摘要】 齐墩果酸(Oleanolic Acid, OA)是一种齐墩果烷型五环三萜类化合物,是多种天然产物的主要功能成分,在自然界中分布广泛,如在青叶胆全草、白花蛇舌草、女贞果实等植物中以游离形式存在或与糖结合成苷存在。显示出多种生物活性：如抗炎、抗肿瘤、降血糖、抗高血脂等药理作用。OA是治疗急性黄胆型肝炎和慢性病毒性肝炎比较理想的药物,且毒性低,不良反应少。由于其药理活性较多,副作用和细胞毒性相对较低,近年来国内外对齐墩果酸的提取、含量测定和药理活性等方面做了大量的研究工作。部分研究小组也对其衍生物的抗肿瘤和抗艾滋病活性进行了研究,但对其衍生物的抗菌活性研究较少。为了更加深入的研究齐墩果酸及其衍生物的生物活性与结构的关系,本文以具有多种生物活性的天然化合物齐墩果酸为先导化合物,以有机化学理论和药物合成原理为指导,以有机合成技术为手段,结合生物活性测试,对其结构进行了修饰和改造,并开发了乙醇酸、丁二酸酐和丁二醇等连接片段,并进行了抑菌活性测试,以期得到高效低毒的齐墩果酸衍生物。本论文的研究主要分为三部分：第一部分：对齐墩果酸的药理作用进行了阐述,介绍了齐墩果酸的研究进展、临床应用及发展前景。第二部分：齐墩果酸衍生物的合成与表征及连接片段的使用。通过探索合成、分离和纯化的条件,设计并合成了35种齐墩果酸衍生物。采用IR、1HNMR等技术对所合成的化合物进行了结构表征,其中有32种化合物未见文献报道。第三部分：对先导化合物齐墩果酸和所合成的衍生物进行了抑菌活性测试。更多还原

【Abstract】 Oleanolic acid is an oleanane-type compound of pentacyclic triterpenoids, and it is the main functional components of various natural products. Oleanolic acid distributes in nature widely, such as swertia mileenis, oldenlandia diffusa, fruit of glossy privet and other plants, with free form existence or with sugar to combine into the glucoside exist. It shows a variety of biological activities such as anti-inflammatory, antitumor, hypoglycemic, anti-high blood cholesterol, and many other kinds of pharmacological effects. Oleanolic acid is a perfect drug to treat acute icterohepatitis and chronic viral hepatitis, and it is in the nature of low toxicity and fewer side effects. Due to its superior pharmacological activities, fewer side effects and lower toxicity, a lot of research work about the extraction, content determination and pharmacological activity of oleanolic acid has been done at home and abroad in recent years. Some of the research teams have studied the derivatives of oieanolic acid on anti-tumor and anti-AIDS activity, but researches on antibacterial activity are very little.In order to study the structure activity relationship of oleanolic acid and its derivatives in depth, this dissertation use oleanolic acid as a lead compound and combine the achievements of biological activity test to modified its structure based on the theories of organic chemistry and pharmaceutical synthesis and the methods of organic synthesis technology. Some derivatives of oleanolic acid were synthesized, and their antibacterial activities were tested in order to obtain high efficiency and low toxicity derivatives of oleanolic acid.Three parts are included in this dissertation.The first part described the pharmacological effects of oleanolic acid and introduced the progress, clinical application and development prospects of oleanolic acid.The second part synthesized and characterized the derivatives of oleanolic acid. By exploring the synthesis, separation and purification conditions,35 kinds of oleanolic acid derivatives were designed and synthesized.32 kinds of the compounds have not been reported. All the structures were characterized by the methods of IR and 1HNMR.The third part tested the antibacterial activity of the oleanolic acid and its derivatives.更多还原