The State Key Laboratory of Chemical Oncogenomics, Guangdong Provincial Key Laboratory of Nano-Micro Materials Research, School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen 518055, China.
Shenzhen Bay Laboratory, Shenzhen 518055, China.
J Am Chem Soc. 2022 Jun 15;144(23):10640-10646. doi: 10.1021/jacs.2c03978. Epub 2022 Jun 2.
Cephanolides A-D are cephalotane-type diterpenoids featuring a novel 6/6/6/5 tetracyclic core embedded with a bridged δ-lactone. The asymmetric and divergent total syntheses of cephanolides A-D have been accomplished, proceeding in 11-14 steps from a known alcohol. The salient features of the present work include (i) a substrate-controlled diastereoselective intermolecular Diels-Alder reaction to form the 6-6 -fused rings, (ii) a palladium-catalyzed formal bimolecular [2 + 2 + 2] cycloaddition reaction via a partially intermolecular cascade reaction sequence involving multiple carbometalations to rapidly install the key tetracyclic skeleton, and (iii) lactonization and late-stage oxidative diversification to complete total syntheses of the four benzenoid cephanolides.
头孢内酯 A-D 是一种具有新型 6/6/6/5 四环核心结构的头孢烷型二萜类化合物，其中嵌入了一个桥接的 δ-内酯。通过从已知醇出发经过 11-14 步反应，实现了头孢内酯 A-D 的不对称和发散式全合成。本工作的显著特点包括：（i）底物控制的非对映选择性分子间 Diels-Alder 反应形成 6-6 稠合环；（ii）钯催化的形式双分子 [2+2+2] 环加成反应通过部分分子间级联反应序列进行，涉及多次碳金属化反应以快速构建关键四环骨架；（iii）内酯化和后期氧化多样化反应完成了四个苯并头孢内酯的全合成。
