Azaphilonoids是一大类含独特共轭多烯酮以及氧（氮）双环核心结构的聚酮类真菌代谢产物，目前已经被分离鉴定370多个化合物。迄今为止，这类具有多种生理活性的天然化合物尚没有被很好地开发应用；且仅有个例不对称全合成报道。主要有两大原因：1）多数绝对立体化学的归属依赖CD光谱和理论计算预测，存在不确定性；2）缺乏有效的不对称合成方法获得这些天然产物的核心骨架。本项目拟在本组对Chlorofusin成功不对称全合成及其方法学研究的基础上，选取此类天然产物中结构相关性较高、尚无全合成报道的三例典型的二聚型天然产物作为目标进行全合成研究，分析探讨其发生二聚的生源基础，由此设计、发展一条合理高效的统一全合成路线，一方面确证这些天然产物化学结构鉴定中存在的疑问，另一方面希望由此发展新的催化不对称方法建立这类化合物的核心结构，为这些重要天然产物的化学合成建立一种通用方法。

Azaphilonoid represents a large natural polyketide family, which features with a common unqiue conjugated polyenone bicyclic core and a wide spectrum of biological activities. More than 370 azaphilonoids were identified from various fungi sources, however, very limited advances have been achieved in modern medicinal research and organic synthesis of these natural products. The current major challenges to the chemist include (1) lacking direct methods to unambigueously elucidate the absolute structures of natural azaphilonoids and most of the present conclusions need to be re-confirmed by total synthesis; and (2) needing efficient asymmetric methodologies to establish the chiral azaphilone core. Continuing our previous accomplishment in the total synthesis of chlorofusin, a cytotoxic complex natural azaphilone-cyclopeptide hybrid, we herein wish to develop a unified route for the total synthesis of three dimeric natural azaphilonoids (chaetoglobins A and B, and cochliodone A) in this project. By analysis of their biogenetic origins, a biomimetic direct sp2 C-sp2 C dimerization and an oxidative dearomatization are designed as the key steps. Such a design will be able to reduce the steps and minimize the use of protecting groups in the total synthesis. Accordingly, both the stereodivergent and stereoselective asymmetric methodologies will be studied for confirmation of the absolute chemistries and final asymmetric total synthesis of these three natural products. The proposed project is expected to provide a general protocol for the structural determination, and chemical synthesis of this class of natural products, as well as their future application in medicinal chemistry.