基于联烯多样反应性能的核苷衍生物的合成、生物活性和荧光性能研究

项目名称： 基于联烯多样反应性能的核苷衍生物的合成、生物活性和荧光性能研究

项目编号： No.21272058

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： 范学森

作者单位： 河南师范大学

项目金额： 80万元

中文摘要： 5-取代嘧啶核苷衍生物因具有显著的生物活性和良好的荧光性能而成为新先导化合物发现的重要来源。目前，该类化合物大多通过钯催化下5-碘代嘧啶核苷与官能团化有机（金属）试剂之间的偶联反应来得到。由于这些偶联反应所用的反应底物难合成、毒性大，所用的催化剂价格昂贵，所能提供的核苷衍生物种类及数量有限，使相关的嘧啶核苷类新药及荧光探针试剂的研究与开发工作受到严重制约。为解决上述问题，本项目拟基于官能团化联烯的丰富反应性能，探索并建立从价廉易得的原料出发、在无需使用贵金属催化剂的条件下合成5-取代嘧啶核苷的新方法。利用这些方法，并以优势结构为导向，设计、合成结构多样化的五元、六元芳（杂）环取代嘧啶核苷和三环嘧啶核苷衍生物。通过研究这些核苷衍生物的抗病毒、抗肿瘤、抗寄生虫等生物活性及荧光性能，希望筛选到具有显著生物活性和良好荧光特征的新先导化合物，为核苷类新药和荧光探针试剂的开发做好物质准备。

中文关键词： 官能团化联烯；嘧啶核苷；合成；生物活性；荧光性能

英文摘要： 5-Substituted pyrimidine nucleoside derivatives are emerging as a rich source in the search for new lead compounds since many of them are biologically active and intrinsically fluorescent. So far, 5-substituted pyrimidine nucleosides are usually synthesized via palladium catalyzed coupling of 5-iodopyrimidine nucleosides with functionalized organo(metallic) reagents. However, the usage of these coupling reactions are compromised due to difficult-to-obtain and toxic substrates they employed, expensive catalysts they used, and limited categories and amounts of products they could produce. In order to solve these problems and inspired by the diverse reactivity of functionalized allenes, this project aims to establish new synthetic methods toward 5-substituted pyrimidine nucleosides from easily available and economical starting materials without using noble metal catalysts. With these new methods, a privileged structure-guided design and synthesis of structurally diverse 5-membered or 6-membered aromatic (heterocyclic) ring substituted pyrimidine nucleosides and tricyclic pyrimidine nucleosides will be accomplished. All the compounds prepared will be screened as antiviral, anticancer and antiparasitic drug candidates and their fluorescent property will also be studied. It is expected that implementation of the propo

英文关键词： functionalized allenes；pyrimidine nucleosides；synthesis；biological activity；fluorescent property