【作者】 张国良；

【导师】 陈长水；

【作者基本信息】 华中农业大学 ， 农药学， 2006， 硕士

【摘要】 糖苷酶抑制剂的研究受到了化学家和生物学家的广泛关注，是因为这类化合物不仅能作为研究寡糖和糖复合物功能的有用工具，而且是潜在的治疗与糖链异常相关的疾病的药物。这些抑制剂主要是氮杂糖类衍生物。氮杂糖类化合物有十分广阔的药物开发前景，特别是作为糖苷酶抑制剂和糖基转移酶抑制剂类药物。目前已发现其可以作为抗HIV、抗癌、抗流感和抗糖尿病等疾病的药物。因此研究此类化合物的合成以及结构和酶抑制活性的关系对于寻找新型药物具有十分重要的意义。 本文综述了近年来氮杂糖类糖苷酶抑制剂的研究进展和氮杂糖的合成方法，总结了糖苷酶抑制剂的构效关系。在此基础上本文设计了基于酶促反应过渡态的半乳糖苷酶抑制剂，采用了醋酸汞介导的氨汞化成环方法，以半乳糖为原料，经过11步的合成路线，拿到了三个互为异构体的半乳糖型氮杂糖母体分子结构。然后将三个母体分子分别进行衍生化，即在其活性位点用不同的侧链进行修饰，经过脱保护得到目标产物，然后进行一系列的活性测试。 本论文共合成了36个化合物，其中有20个未见文献报道。所有新化合物均经¹HNMR、¹³CNMR、MS、元素分析或者HRMS确定结构。更多还原

【Abstract】 Inhibitors of glycosidases have been attractive compounds for synthetic chemists and biochemists, not only because they serve as useful biological tools for studying the biological functions of oligosaccharides but also they may have great potential as drugs to treat a variety of carbohydrate-mediated diseases. They are now finding clinical applications as anti-HIV, anti-cancer, anti-flu and anti-diabetic agents. Therefore it’s very important to synthesize glycosidase inhibitors for finding new drugs.In this thesis, the structure-activity relationships of the known glycosidase inhibitors and the typical synthetic methods of iminosugars were reviewed. Based on the transition-state of the enzyme-catalyzed reactions, some iminosugar derivatives were designed and synthesized.Utilizing the mercury acetate-mediated cyclization reaction, 3 iminosugars were isolated via 11 steps starting from galactose. The configurations of three isomers were identified using NMR technique. And then some nitrogen-substituted derivatives were prepared.36 compounds were synthesized in this thesis and 20 of them were unknown. All these new compounds were characterized by their ¹H NMR, ¹³C NMR, MS, HRMS/elemental analysis.更多还原