D/E环官能团化的齐墩果烷型活性三萜皂苷的合成研究

As an important subgroup of triterpen saponins, D/E-ring-functionalized oleanane-type saponins have been proven to possess a diversity of bioactivities including antitumoral, hypoglycemic, and pancreatic lipase-inhibitory activities, thus having the promise to be pharmaceutically applied. Impeded by the difficult access of the D/E-ring-functionalized oleanane-type aglycons, the development of D/E-ring-functionalized oleanane-type saponins synthesis proceeds sluggishly, which retards the pharmaceutical application process of these valuable compounds. In this project, we plan to launch a program to investigate the first total synthesis of albiziaside B，concinnoside D, and dumortierinoside A, the three types of typical representatives of D/E-ring-functionalized oleanane-type saponins. Through the synthetic investigation, a diversity-oriented method to generate D/E-ring-functionalized oleanane-type aglycons as well as an efficient approach to construct saponin glycan chain by MPEP glycosylation protocol can be found out, thus setting up a highly efficient strategy to produce D/E-ring-functionalized oleanane-type saponins. As a result, the difficulty associated with sample acquisition will be solved, which will promote the following structure-activity-relationship as well as working mechanism investigations and speed up the pharmaceutical application process of D/E-ring-functionalized oleanane-type saponins.

D/E环官能团化的齐墩果烷型三萜皂苷作为三萜皂苷的重要组成部分表现出抗肿瘤、降糖、降低胰脂肪酶活性等生物活性，因此具有良好的成药前景。但受到D/E环官能团化的齐墩果烷型三萜甙元获取困难的限制，D/E环官能团化的齐墩果烷型活性三萜皂苷的合成研究发展缓慢，从而严重制约了其药用进程。本课题拟开展D/E环官能团化的齐墩果烷型活性三萜皂苷典型代表albiziaside B，concinnoside D 以及dumortierinoside A的合成研究，以期建立D/E环官能团化的齐墩果烷型三萜甙元的多样化合成路线以及MPEP给体高效合成皂苷糖链的方法，确立高效合成D/E环官能团化的齐墩果型三萜皂苷的策略。从而从根本上解决该类活性皂苷样品获取难题，促进后续构效关系及作用机制研究，加快成药进程。

D/E环官能团化的齐墩果烷型三萜皂苷作为三萜皂苷的重要组成部分表现出抗肿瘤、降糖、降低胰脂肪酶活性等生物活性，因此具有良好的成药前景。但受到D/E环官能团化的齐墩果烷型三萜甙元获取困难的限制，D/E环官能团化的齐墩果烷型活性三萜皂苷的合成研究发展缓慢，从而严重制约了其药用进程。本项目以原七叶皂苷元为原料，通过一系列化学反应先实现了免疫佐剂QS-21苷元的化学合成及左侧糖链的高效构建，随后又实现了具有活性的天然三萜皂苷Concinnoside D和Dumortierinoside A的首次全合成研究。该项目的成功确立了高效合成D/E环官能团化的齐墩果型三萜皂苷的策略，从而从根本上解决该类活性皂苷样品获取难题，促进后续构效关系及作用机制研究，加快成药进程。