高价碘试剂为媒介的新型二氢卟吩光敏剂的选择性合成及其光动力活性研究

项目名称： 高价碘试剂为媒介的新型二氢卟吩光敏剂的选择性合成及其光动力活性研究

项目编号： No.21202201

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 有机化学

项目作者： 欧阳勤

作者单位： 中国人民解放军第三军医大学

项目金额： 25万元

中文摘要： 二氢卟吩类光敏剂在光动力治疗（PDT）癌症上具有肿瘤选择性好、活性高等优点。合成结构新颖的二氢卟吩衍生物是进一步提高光动力学治疗效果、开发新型高效光敏剂的有效途径。据文献报道，金属卟啉在高价碘试剂作用下形成自由基阳离子中间体，再发生区域选择性的偶联或取代反应，能简便高效的合成不同功能化卟啉衍生物。二氢卟吩具有与卟啉相似的共轭特点、氧化还原性质，有望通过此类反应拓展其结构类型。前期研究证实，高价碘试剂与二氢卟吩锌配合物反应能够以70%的收率选择性的合成20-20'直接键连二氢卟吩，其光物理学性质符合理想光敏剂对作用光谱的要求。本项目拟研究二氢卟吩金属络合物在高价碘试剂媒介下的选择性偶联及取代反应，合成各种功能化的新型二氢卟吩衍生物。基于以上合成方法，制备适用于光动力学治疗的新型二氢卟吩衍生物，通过体外癌细胞培养及光敏剂活性测试，结合其光谱性质研究构效关系，为发现新型高效的光敏剂奠定基础。

中文关键词： 二氢卟吩；光敏剂；光动力治疗；高价碘试剂；肿瘤

英文摘要： There is increasing interest in photodynamic therapy (PDT), as an anti-cancer strategy for the treatment of shallow small localized tumors. Among the different photosensitizers currently available, the several chlorins have received approval for clinic. Various chlorin-based structures have been developed in order to increase the photoefficiency. However, the functionalization of chlorins for developing new structures was limited because of their hard synthesis and inferior stability. As reported, hypervalent iodine-mediated oxidative coupling and nucleophilic substitution reaction was developed for synthesis of directly linked porphyrin dimer and meso-amino or meso-arylsulfanyl-substituted porphyrins. The mechanism for porphyrin to carry out those reactions was widely considered as involving single eletron transfer (SET) oxidation. The porphyrin radical cation, producing via SET oxidation, couples itself to form dimer or reacts with nucleophilic reagents to achieve meso-functionalization. Comprising with porphyrin, chlorin has the similar conjugate and redox properties but with one reduced pyrrole (i.e., pyrroline) ring. Therefore, we infer that similar oxidative coupling and nucleophilic substitution reaction of chlorin can be carried out if the oxidation of pyrroline ring could be avoided. The deduction and f

英文关键词： chlorins；photosensitizers；photodynamic therapy；hypervalent iodine regent；cancer