天然产物Anditomin和Andilesins的对映选择性全合成研究

Andilesins以及anditomin等天然产物是从杂色曲霉中分离出来的一类结构新颖独特的真菌杂萜天然产物。它们大多含有高度稠合的6/5/6/5多环体系、高张力的[2.2.2]桥环核心骨架以及密集的立体化学中心(包括5个季碳中心)。这些都为该类分子的合成带来了很大的挑战。到目前为止，此类分子的全合成尚未见报道。本项目选取其中代表性的andilesins A-D, andiconin B, 以及anditomin等6个天然产物作为合成目标，拟使用汇聚式的合成策略，通过Claisen重排、串联Diels-Alder反应、C-H键氧化等关键反应来实现该类结构中复杂环系骨架的构建，并进一步考察这几类结构之间的仿生转化关系。拟通过一条通用的合成路线，集群式地实现6个天然产物的不对称全合成。除此之外，本课题还将围绕上述合成工作得到的若干具有结构多样性的“天然产物库”展开初步的生物功能研究。

Andilesins and Anditomin are structurally complex meroterpenoids that isolated from Aspergillus variecolor. Their structure features of polycyclic ring system, sterically congested carbon centers (including 5 quaternary ones). The efficient construction of those intriguing natural products offers a formidable synthetic challenge. To date, no total synthesis for this class of compounds can be found in the literature. In this proposal, we intend to develop a convergent synthetic strategy towards the total synthesis of six related natural products including andilesin A-D, andiconin, and anditomin. In this project, a series of key reactions such as Claisen rearrangement, tandem Diels-Alder reaction and late-stage C-H oxidation are intended to be involved in this process. Theoretically, our strategy allows for the rapid access to several representative skeletons of this family of natural products from a common intermediate, which paves the way to a collective synthesis of various targets and their analogs. Studies toward the structure-activity relationship (SAR) of intermediates and analogs will also be conducted in this research.