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.
Angew Chem Int Ed Engl. 2023 Jun 5;62(23):e202303402. doi: 10.1002/anie.202303402. Epub 2023 Apr 26.
The daphnezomine A-type subfamily of Daphniphyllum alkaloids structurally features a unique aza-adamantane core skeleton and anticipates efficient strategies for completing their syntheses to thoroughly investigate their biological activities. Herein, divergent total syntheses of (-)-daphnezomines A and B and (+)-dapholdhamine B have been accomplished in 16-20 steps from a known epoxide via rapid construction of a common core intermediate. The present work features a Ti-mediated radical cyclization to establish the azabicyclo[3.3.1]nonane ring system, an intramolecular Heck reaction to install the bridgehead all-carbon quaternary stereocenter, a tandem deprotection/reduction/keto amine-carbinolamine tautomerization to furnish the aza-adamantane backbone, and an NIS-promoted 6-endo-trig aminocyclization to assemble the (+)-dapholdhamine B backbone.
该文报道了一组从已知环氧化合物出发经 16-20 步反应完成(-)-daphnezomine A 和 B 及 (+)-dapholdhamine B 的全合成。该路线关键步骤包括 Ti 介导的自由基环化反应构建氮杂双环[3.3.1]壬烷环系，分子内 Heck 反应构筑桥头碳季碳中心，串联脱保护/还原/酮胺-碳宾胺互变异构构筑氮杂金刚烷核骨架，NIS 促进的 6-endo-trig 氮杂环化构建(+)-dapholdhamine B 骨架。
