Actinophyllic Acid类含七元环的复杂多环活性天然产物全合成研究

项目名称： Actinophyllic Acid类含七元环的复杂多环活性天然产物全合成研究

项目编号： No.21472078

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 无机化学

项目作者： 李瀛

作者单位： 兰州大学

项目金额： 90万元

中文摘要： 七元环天然产物Actinophyllic Acid、Ervatamine、Silicine、Eivisine具有良好的生物活性。Gelsemine生物碱的分离植物是中国的传统药物，其提取物是治疗癌症的临床药物。[4+3]环加成在快速构筑含有七元环的多环骨架的广泛适用性和高效性而受到关注。本项目以含有七元环的活性天然产物Actinophyllic Acid及Silicine、Eivisine的全合成，Gelsemine、Gelsedine和Gelsemicine的核心骨架构筑为研究目标，在深入拓展本课题组关于[4+3]环加成方法学研究的基础上，通过拓展该反应适用范围及串联分子内环醚化反应来实现七元环骨架的快速高效构筑。进而将该方法应用到上述6个天然产物的核心骨架构筑或者全合成研究中，开发一条新的高效简洁、适用范围广的合成各类七元环活性天然产物的方法，为该类化合物的开发应用打下基础。

中文关键词： [4+3]环加成；天然产物全合成；Actinophyllic；Acid；生物活性；构效关系

英文摘要： The bioactivity study of seven-membered ring natural products (Actinophyllic Acid, Ervatamine, Silicine, Eivisine) shows they are inhibition of deacetylase SIRT1, inhibition of adipocyte fatty-acid-binding protein (A-FABP) and antitubercular activity. Gelsemine, a major alkaloid component of Gelsemium sempervirens, was first isolated in 1876. The plant is a Chinese traditional medicines, the extract is the treatment of cancer in clinical drug. [4 +3] cycloaddition is an efficient, simple yet elegant strategy, which was highly concerned about because of the applicability and efficiency in rapid building complex seven-membered ring containing polycyclic skeleton. This project is mainly focusing on the total synthesis of Actinophyllic Acid, Silicine, and Eivisine,as well as the key skeleton of Gelsemine, Gelsedine and Gelsemicine. On the basis of In-depth expansion of our group studies in [4 +3] cycloaddition methodology, we'll achieve facile and efficient building of seven-membered ring polycyclic skeleton by expanding the scope of the series of molecular reactions and achieving intramolecular etherification. Furthermore, the method is applied to the synthesis of core skeleton or total synthesis of above 6 natural products. We'll develop a facile, efficient and widely applied methods in synthesis of various bioactive natural products containing 7-membered rings, which will lay the foundation for the development and application of these compounds.

英文关键词： [4+3]cycloaddition;Natural products total synthesis;Actinophyllic Acid;bioactivity;structure activity relationship (SAP)