欧亚旋覆花中Diels-Alder型二聚倍半萜的发现及其生物活性研究

Dimeric sesquiterpenes, often functionally and stereochemically rich with impressive biological profiles, have been a real explosion of interest in natural product field. Inula britanica L., belonging to the genus Inula in the Compositae family, is an economically and medicinally important perennial herb, and one of the two official species of traditional Chinese herb Flos Inulae (Xuan Fu Hua). Regrettably, previous phytochemical investigations on the minor Diels-Alder reaction type dimeric sesquiterpenes from the genus plants were weak. Relatively few cases existed for solving their absolute configurations, and the stereochemical assignments could not lead to the equivocal conclusions. In addition, the researches into the bioactivity still remain to be carried out further. Therefore, based on the proposed biosynthetic pathways of the isolated dimers, the goal of this program is to track and afford the desired sesquiterpene dimers with diverse structural scaffolds from the aerial parts of I. britanica, coupled with the integrated LC-DAD-MSn dereplication and NP/RP-pHPLC rational separation strategies. Meanwhile, the stereochemical problems including the absolute configuration are comprehensively addressed to develop the suitable spectroscopic and chiroptical methods for the configurational assignments. And their antitumor and anti-inflammatory activities are studied in depth to further reveal the structure-activity relationships (SARs) and explore the mechanism of biological activities. The present study will expand the utility, potential and development of this medicinal plant, and will definitely facilitate the further chemical investigation into the Diels-Alder reaction type sesquiterpene dimers derived from the genus Inula.

二聚倍半萜类以其新颖复杂的结构骨架和显著的生物活性，正在成为天然产物研究的热点之一。欧亚旋覆花（Inula britanica L.）为菊科旋覆花属的药用植物，是中药旋覆花的基原植物之一。本课题针对目前旋覆花属中Diels-Alder型二聚倍半萜类化学成分研究不足、立体构型多未阐明、相关生物活性研究不够深入等现状，以基于生物合成途径的推测为切入点，开展以LC/DAD/MSn去重复化为手段的欧亚旋覆花中微量、新颖的D-A型二聚倍半萜类定向寻找，进一步采用正/反相二维正交色谱和制备液相色谱技术高效分离的研究。在化合物平面结构基础上，重点研究其立体结构，包括绝对构型的确定，揭示波谱学和手性光谱学规律；对该类化合物抗肿瘤、抗炎的构效关系和作用机制进行探讨。上述研究成果将促进欧亚旋覆花药用植物的进一步开发和利用，为旋覆花属植物中D-A型二聚倍半萜类的成分和结构研究提供参考。