过渡金属催化的[3+2]环加成构筑杂糖核苷及异核苷类化合物

杂糖核苷和异核苷类化合物具有显著的抗肿瘤和抗病毒活性，这些非天然核苷可以有效地嵌入肿瘤和病毒的DNA链，并终止其DNA链的延伸达到治疗疾病的目的。据统计世界上已经有70多种非天然核苷化合物被开发为抗肿瘤和抗病毒药物，其中包含杂糖核苷和异核苷类化合物。因此开展对该类化合物的合成及活性测试具有重要的理论意义和应用价值。到目前为止，该类化合物的报道较少、化合物的多样性不足、合成步骤长、收率低。因此设计合成结构新颖、多样性广泛、能够便捷合成的杂糖核苷和异核苷类化合物就成为一个不可忽视的课题。本课题组一直从事核苷（酸）类似物的结构修饰，合成了400多种新的核苷类化合物，积累了丰富的经验。本项目拟用过渡金属催化的[3+2]环加成反应合成一系列杂糖核苷和异核苷类化合物，并进一步衍生为一系列杂糖核苷酸及异核苷酸类化合物，建立相应的化合物库，并测试其抗肿瘤活性和抗病毒活性。以期发现具有抗肿瘤与抗病毒活性的先

Pesudosugar nucleosides and isonucleosides possess significant antitumor and antiviral activities. These unnatural nucleosides were employed to treat diseases by incorporating into DNA chains to terminate the extending of DNA chains. According to statistics, there are nearly 70 unnatural nucleosides were developed into antitumor and antiviral drugs including many pesudosugar nucleosides and isonucleosides. So it is of theoretical and applicable importance on the synthesis and activity-testing of the compounds. However, the current synthesis processes have some faults, such as, multi steps and low yields. It is a very important task to overcome these deficiencies and then synthesize the pesudosugar nucleosides and isonucleosides with novel structure. In recent years, we have been working on modification of purine nucleosides, synthesizing more than 400 nucleosides. This project aims to synthesize a series of unnatural nucleosides (pesudosugar nucleosides and isonucleosides) by the [3+2] cycloaddition catalyzed by transition metals, constructing the pesudosugar nucleosides and isonucleosides libraries, and extending the scope of nucleosides. The obtained unnatural nucleosides will be tested antitumor and antiviral activity, and investigated the structure-activity relationship and mechanism, in order to find the lead compounds with antitumor and antiviral activity.