与DMDP结构相关的天然亚氨基糖的合成及其生物活性研究

项目名称： 与DMDP结构相关的天然亚氨基糖的合成及其生物活性研究

项目编号： No.21272240

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 俞初一

作者单位： 中国科学院化学研究所

项目金额： 80万元

中文摘要： 亚氨基糖是一类重要的生物活性糖模仿物，其中有许多是高效高选择性的糖苷酶或糖基转移酶抑制剂，在治疗糖尿病、抗癌和抗病毒等新药创制中显示出潜在的巨大应用价值。在迄今已分离到的二百余个天然亚氨基糖生物碱中，吡咯烷类生物碱DMDP是具有代表性的一个：它具有重要的生物活性如糖苷酶抑制活性和杀虫活性；有三十余个天然亚氨基糖生物碱在结构上与其相关，其分子中都含有一个环上全反式取代的吡咯烷分子片段。研究此类生物碱的合成方法并系统评价其生物活性具有重要的意义，有望发现新的药物先导化合物。本课题旨在研究和发展一种以环状硝酮为合成中间体的合成方法。目标是建立一种简便、高效和通用的合成此类生物碱的方法，为系统研究这类化合物的构效关系打下基础。研究内容包括：与DMDP结构相关的多羟基吡咯烷类生物碱的合成、与DMDP结构相关的多羟基双稠吡咯烷类生物碱的合成，以及系统评价所合成化合物的生物活性。

中文关键词： 亚氨基糖；DMDP；多羟基环状硝酮；构效关系；糖苷酶抑制剂

英文摘要： Iminosugars, also refered to as azasugars or polyhydroxylated alkaloids, are an important class of carbohydrate mimetics which posess interesting biological activities. Many iminosugars are found to be inhibitors against glycosidases or glycosyltranferases, and therefore are potentially valuable in the development of new agents for the treatment of many diseases, such as diabetes, cancer and viral infection etc. More than two hundred naturally-ocurring iminosugars have so far been isolated from plants or bacteria. DMDP, the polyhydroxylated pyrrolidine alkaloid with an C2-symmetric and all-trans pyrrolindine ring in its molecule, is a special member in the iminosugar family in that more than thirty naturally-ocurring iminosugars are structurally related to it and can be considered as its deritives. Since DMDP and DMDP-related iminosugars have exhibited some important biological activities and are potentially useful in drug discovery, it is significent to develop efficient synthetic methods for the access of these compounds. The in-depth study on the synthesis and biological evaluation of this kind of iminosugars could be resulted in the discovery of new drug lead compounds. This project is intented to develop a general method for the synthesis of DMDP-related iminosugars with sugar-derived cyclic nitrones as key

英文关键词： iminosugar；DMDP；sugar-derived nitrone；Structure-Activity Relationship；glycosidase inhibitor