牛蒡子中Arctignan A，Lappaol C及其衍生物的合成和抗白血病活性研究

项目名称： 牛蒡子中Arctignan A，Lappaol C及其衍生物的合成和抗白血病活性研究

项目编号： No.21472105

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： 夏亚穆

作者单位： 青岛科技大学

项目金额： 80万元

中文摘要： 以天然产物为基源，从中发现先导化合物，进而优化结构，是创制新药的有效途径。现代研究表明，中药牛蒡子抗癌效果明显，在其活性成分倍半木脂素中可能发现抗白血病作用强烈的先导化合物。而且，倍半木脂素结构新颖，目前临床抗癌药物中未发现相似骨架类型，有望从中开发出新型药物。 本项目对牛蒡子中8-O-4′型倍半木脂素(-)-Arctignan A和8-3′型倍半木脂素(-)-Lappaol C及其衍生物进行不对称合成和生物活性研究。涉及的倍半木脂素均为首次合成，而且尚未发现此类化合物系统的抗白血病活性研究报道。本项目首次从化合物合成、细胞药效学、构效关系、分子作用机制等方面，多层次、多角度地研究了牛蒡子中倍半木脂素化合物，为创制新型抗白血病药物提供理论与实践依据。开展此项工作，可深入挖掘倍半木脂素的药用价值，丰富天然产物的不对称合成方法，促进我国药物化学研究发展。

中文关键词： Arctignan；A；Lappaol；C；牛蒡子；合成；抗白血病活性

英文摘要： An effective method of new drug discovery is the structure optimization of the lead compounds, which were found from nature products. Modern research indicates that the traditional Chinese herbal medicine Fructus Arctii，in which sesquilignans are important active components, exhibits significant anti-cancer activities, and the lead compound with the strong anti-leukemia activity may be found in the sesquilignans. Moreover, the structures of sesquilignans from Fructus Arctii are novel, haven't been found similar with the drugs that were used in clinical treatment, and new types of drugs may be discovered and formulated in sesquilignans. In this project, the asymmetric synthesis and biological activity of (-)-Arctignan A, (-)-Lappaol C and their derivatives, which respectively belong to 8-O-4' and 8-3′-type sesquilignans isolated from Fructus Arctii, are studied. So far, the asymmetric synthesis and the systematical studies on the anti-leukemia activity of the sesquilignans have not been reported. In our work, we plan to get the target compounds via the asymmetric total synthesis, then test their anti-leukemia activities, explore the structure-activity relationships and deeply discuss the function mechanism. The studies mentioned above will provide theoretical and practical basis for research and production of new anti-leukemia drug. The implementation of this project will extract the medicinal value of the sesquilignans, enrich the methods of the asymmetric synthesis of natural products and promote the development of medicinal chemistry in our country.

英文关键词： Arctignan A;Lappaol C;Fructus Arctii;Synthesis;Anti-leukemia Activity