“含全碳季碳的氢化并四苯”的不对称构建及其在Naphthacemycin型芳香聚酮合成中的应用研究

“含全碳季碳的氢化并四苯”是广泛存在于芳香聚酮天然产物中的一类线型稠合的环状结构，其不对称合成一直受到有机合成化学家的青睐。然而，由于稠环自身的张力与全碳季碳手性中心的存在，给其合成带来较大的挑战。目前，针对该结构单元不对称催化的一步式合成研究较少。本项目拟以“含全碳季碳的氢化并四苯”的不对称构建为研究目标，基于去对称化策略，设计、发展新颖的1,3-茚二酮分子内不对称催化的Büchner–Curtius–Schlotterbeck反应，实现氢化并四苯一步式立体选择性构建。再以此为关键反应，设计简洁、高效的合成路线，探索发展芳香聚酮Naphthacemycin C2的不对称全合成。该项目拟开展工作不仅可以丰富五元环酮不对称催化的同系化反应，还将为“含全碳季碳的氢化并四苯”单元的不对称催化构建提供新策略，在一定程度上，还将展示出不对称催化方法学在天然产物与药物分子全合成中的应用价值。

Hydrotetracenes with all-carbons quaternary stereocenters as a kind of important fused ring structures widely exist in natural products. The asymmetric synthesis of these units has attracted much attention from the synthetic community. However, due to the existence of ring strain and all-carbon quaternary stereocenters, the asymmetric catalytic one-step synthesis of these skeletons is a challenge issue and remains elusive. Hence, the development of alternative asymmetric catalytic methodologies to construct hydrotetracenes is highly desirable. In this project, we focus on the design of novel enantioselective Büchner–Curtius–Schlotterbeck reaction of 1,3-indandiones under the catalysis of chiral Lewis acids, achieving a one-step stereoselective synthesis of the title fused rings. On the basis of this key asymmetric methodology, simple and efficient synthetic routes have been designed to explore asymmetric total synthesis of Naphthacemycin C2. It is expected that this research will not only enriches asymmetric catalytic homologation reaction of five-membered cyclic ketones, but also provides a new strategy for the asymmetric catalytic construction of hydrotetracenes with all-carbon quaternary stereocenters. Moreover, this project will demonstrate the application value of asymmetric catalytic methodology in the total synthesis of natural products and pharmaceuticals.