基于9-联烯嘌呤构建环状大小不同的手性碳环核苷

项目名称： 基于9-联烯嘌呤构建环状大小不同的手性碳环核苷

项目编号： No.21472037

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 郭海明

作者单位： 河南师范大学

项目金额： 90万元

中文摘要： 碳环核苷作为核苷的类似物在结构上比核苷更具稳定性，在抗病毒、抗肿瘤活性等方面具有更广阔的应用前景。手性碳环的构筑是该类化合物合成的关键，但目前的合成方法存在反应步骤多、手性源不易得到、选择性差、总收率低等不足之处。因此，建立更加高效的手性碳环核苷的合成方法是一个非常有意义的研究课题。申请人近年来一直从事核苷类似物的设计合成及选择性结构修饰，并以9-联烯嘌呤为原料设计合成了系列非环核苷类化合物，对9-联烯嘌呤的反应活性及区域选择性有深入的了解。本项目拟以9-联烯嘌呤为原料，通过不对称[2+1]、[2+2]、[3+2]、[4+2]等环加成反应，选择不同催化体系，调控联烯双键的反应位点，构建三元、四元、五元和六元手性碳环核苷化合物，并进一步衍生得到系列手性碳环核苷酸类化合物，进而建立碳环核苷(核酸)类化合物库，总结合成的方法学，并对其药理活性进行初步研究。

中文关键词： 手性碳环核苷；核苷酸；9-联烯嘌呤；环加成

英文摘要： Carbocyclic nucleosides, as analogues of nucleosides, are more stable than nucleosides, which possess a promising application prospect in antiviral and anticancer activities. For the synthesis of carbocyclic nucleosides, the key point is the construction of chiral carbocyclic rings. However, the reports have many disadvantages including long steps, unavalability of chiral starting materials, poor selectivities, and low total yields. Therefore, it is of great importance to built more effective synthetic methods to construct chiral carbocyclic nucleosides. In recent years, the applicant is focus on the design and synthesis of nucleoside analogues and selective modification. With 9-allenyl-9H-purines as starting materials, a series of acyclic nucleoside analogues have been designed and synthesized successfully. And the reactivity and regioselectivity of 9-allenyl-9H-purines have been known and grasped well. In this project, with 9-allenyl-9H-purines as starting material, we will synthesize three-, four-, five-, and six-membered chiral carbocyclic nucleoside analogues via asymmetric [2+1], [2+2], [3+2], [4+2] cycloaddition reactions. To achieve this goal, we will search different catalytic systems to control the reaction sites of double bond in allene group. By further derivation, the corresponding chiral carbocyclic nucleotide analogues will be obtained. And the compound library of carbocyclic nucleoside and nucleotide analogues will also be built. Finally, we will summarize the synthetic methodology and carry out the preliminary biological activities studies.

英文关键词： Chiral Carbocyclic Nucleosides;nucleotides;9-Allenyl-9H-purines;cycloaddition