本项目拟以手性仲胺催化的不对称自由基历程氧化偶联反应新方法学研究，合成100余个新型的、结构多样化的基于天然产物chartelline和chartellamide骨架手性化合物，并应用于chartelline和chartellamide的全合成中。研究新型化合物的体内外抗肿瘤活性与构效关系、抗肿瘤p53-MDM2结合抑制机制，探索其多靶点机制, 并对其构效关系进行进一步研究。计划筛选出2种以上基于chartelline和chartellamide骨架高活性先导化合物，为以后更深入创制化学新药打下基础。期待为肿瘤疾病的治疗发现潜在的新靶点，为治疗肿瘤疾病创新药物的设计提供新的思路。

This project aims at the development of new methodologies by using chiral secondary amine-catalyzed asymmetric oxidative coupling reactions via radical pathway. In this project, we plan to synthesize at least 100 new chiral compounds with structural diversity based on the backbones of natural products of chartelline and chartellamide. Furthermore, application of the methodologies in the total syntheses of chartelline and chartellamide will be practiced..Moreover, in order to demonstrate the pharmacokinetics and bioavailability, studies of the in vivo and in vitro anti-tumor activities and the structure-activity relationship of these new compounds will be carried out accordingly. .Thus, more than 2 types of lead compounds with good activity featuring the chartelline and chartellamide skeletons will be found, which will lay the solid foundation for further new chemical drugs development..Finally, we look forward to find potential new targets from performing this project, thus to provide the new clues to the design of new drugs for the treatment of tumor diseases.