三尖杉二萜天然产物的集体全合成

中药三尖杉的萜类成分具有优异的抗癌以及广谱的抗菌、抗病毒活性，其结构根据A环不同可以分为benzenoids/A6和troponoids/A7两大类。三尖杉二萜天然产物的结构复杂，且自然界中含量很低，阻碍了进一步的结构改造和生物活性评价。目前对benzenoids/A6和troponoids/A7型天然产物的全合成各有3例成功的报道，但是还没有策略能够实现这两类天然产物的集体合成或相互转化。 .本项目针对以上问题，预实验通过5步反应成功合成了三尖杉二萜的关键骨架，后续拟通过官能团的调整完成多个benzenoids/A6型天然产物的全合成。并通过发展苯酚扩环策略，将benzenoids/A6型中间体转化为troponoid/A7型，实现两类天然产物的集体合成，提高整体合成效率。本项目的实施，将为两种类型三尖杉二萜天然产物提供通用高效的合成方法，为进一步的药物化学和化学生物学研究打下坚实基础。

The terpenoid ingredients of the traditional Chinese medicine cephalotaxus fortunei represent a fascinating class of natural products with broad anticancer, antibacterial and antiviral activities. Structurally, they can be subcategorized as benzenoids/A6 and troponoids/A7 types depending on the difference of the size of A ring. The cephalotaxus diterpenoids have very complex architectures with low abundance in nature, which prevented further therapeutic investigations such as structure-activity analysis, structure modification and biological target identification and verification. So far, there are 3 successful synthetic routes for each of the benzenoids/A6 and troponoids/A7 type diterpenoids, while none of the current strategies targeted both the benzenoids/A6 and the troponoids/A7 types collectively or their interconversions..This research program is set to take this challenge with a new strategy inspired by nature. In initial efforts, the complete benzenoids/A6 cephalotaxus framework was successfully constructed in only five steps. From here, this program is going to aim to finish the total synthesis of several benzenoids/A6 type natural products by simple functional group transformations. Consequently, the strategy of phenol aromatic ring-expansion will be investigated as a key to facilitate the transformation of benzenoids to troponoids, thus to realize the total synthesis of benzenoids/A6 and troponoids/A7 type natural products collectively and improve the overall synthetic efficiency. Successful execution of this research program will not only provide a concise and practical way to afford both types of the cephalotaxus diterpenoids in a unified manner, but also lay the foundation for further biological studies and therapeutic evaluations.