联合生物合成途径与LC-MS策略的新颖萜类聚合物的发现及α-葡萄糖苷酶抑制活性研究

萜类聚合物由于其骨架的新颖性、生物合成途径的独特性以及生物活性的多样性一直是天然产物研究的热门话题。杉科植物主含萜类成分，且二萜二聚体和二萜与单萜聚合而成的C30聚合物是其特征成分。前期研究中发现池杉种子不仅富含萜类聚合物，且具有α-葡萄糖苷酶抑制活性。本项目已分离得到一个含有恶唑环的二萜二聚体（TA-11）和一个C30聚合物（TA-12），初筛结果显示二者都具有显著的α-葡萄糖苷酶抑制活性。为发现更多活性显著的萜类聚合物，本项目联合生物合成途径与HPLC-MS，结合现代色谱手段和技术，设计一条高效的萜类聚合物的富集和纯化方法；综合利用波谱信息、单晶衍射等方法确定新颖化合物的相对构型和绝对构型；对分离得到的化合物利用糖苷酶模型和虚拟筛选进行α-葡萄糖苷酶抑制活性的评价。本项目致力于发现结构新颖活性显著的萜类聚合物，为新型α-葡萄糖苷酶抑制剂的研发提供先导化合物。

Terpenoid polymers have always been a hot topic in the research of natural products due to their novel skeletons, unique biosynthetic pathways and diversity of biological activities. The plants of Taxodiaceae mainly contains terpenoids, and diterpenoid dimers and C30 terpenoid polymers formed by the polymerization of a diterpenoid and a monoterpenoid are its characteristic constituents. In previous studies, it was found that the seeds of Taxodium ascendens were not only contained terpenoid polymers richly, but also it could inhibit α-glucosidase activity. In this project, a diterpene dimer (TA-11) containing an oxazole ring and a C30 terpene polymer (TA-12) have been isolated, and the preliminary screening results showed that both of them revealed significant α-glucosidase inhibitory activity. In order to find more terpenoid polymers with significant activity, this project combined biosynthetic pathway with HPLC-MS, combined with modern chromatography means and technology to design an efficient enrichment and purification method for terpenoid polymers. The relative and absolute configurations of the novel compounds were determined by means of spectrum information and single crystal diffraction. The α-glucosidase inhibitory activity of the isolated compounds were evaluated by using the glycosidase model and virtual screening. This project is dedicated to the discovery of terpenoid polymers with novel structure and significant activity, which will provide lead compounds for the development of novel α-glucosidase inhibitors.