基于一枝蒿酮酸的结构修饰的催化胺化方法学研究

项目名称： 基于一枝蒿酮酸的结构修饰的催化胺化方法学研究

项目编号： No.U1403301

项目类型： 联合基金项目

立项/批准年度： 2015

项目学科： 管理科学

项目作者： 卢崇道

作者单位： 中国科学院新疆理化技术研究所

项目金额： 100万元

中文摘要： 新疆一枝蒿作为新疆维吾尔族民间传统用药历史悠久，该药用植物中含有较丰富的一枝蒿酮酸。本研究室对一枝蒿酮酸进行相对简单的结构衍生后，发现部分一枝蒿酮酸的酯类和酰胺类衍生物具有较好的抗A型流感病毒活性。继续寻找活性高且毒副作用小的一枝蒿酮酸衍生物，是研究基于一枝蒿酮酸的新型抗流感药物（或其他类药物）的关键，对于开发和利用该类新疆特有药用植物资源具有重要意义。在目前上市的神经氨酸酶抑制剂类抗流感药物的分子结构中，均具有高度氮原子和氧原子官能化的环状结构，以此为启发，本研究拟发展适用于一枝蒿酮酸环状骨架上的适当官能化的方法学，主要是碳氢键的催化胺基化方法，其中包括设计和合成新型铑配合物，使其可以作为催化剂用于快速、高效、高选择性和高官能团耐受性的对一枝蒿酮酸分子进行胺基官能化方法学。研究将为实现一枝蒿酮酸（或其衍生物）的分子结构的胺化修饰提供有效的方法学上的支撑。

中文关键词： 一枝蒿酮酸；结构修饰；催化；胺化；方法学

英文摘要： Artemisia rupestris L. has a long history of serving as traditional Uyghur folk medicine in Xinjiang, in which Rupestonic acid presents in relatively large amount. Ester and amide derivatives of Rupestonic acid had been prepared via relatively simple structural modifications in our department, among these derivatives several compounds have been found to be effective against influenza A viruses. Exploration of novel Rupestonic acid derivatives with pronounced activity and low toxicity is a key for the development of new anti-influenza drugs (or other drugs) based on Rupestonic acid as well as for the exploitation and application of the resource of this Xinjiang medicinal plant. The current commercially available anti-influenza drugs that function as neuraminidase inhibitors possess highly oxygen- and nitrogenfunctionalized.ring structures. Inspired by the structural features of these drugs, this project aims to explore effective methods that are suitable for the functionalization of the ring skeleton of Rupestonic acid. The main focus on the studies of the methodologies are catalytic C－H aminations including design, synthesis of the novel complexes that bear a high potential as catalysts for rapid, efficient and highly selective and functional group tolerating incorporation of amino groups into Rupestonic acid. These studies will provide effective methodologies for the structural modification (amination) of Rupestonic acid and its derivatives.

英文关键词： Rupestonic acid;structural modification;catalytic;amination;methodology