Shanghai Key Laboratory of Green Chemistry and Chemical, Processes, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.
Angew Chem Int Ed Engl. 2021 Jun 1;60(23):12807-12812. doi: 10.1002/anie.202102643. Epub 2021 May 5.
We report herein the asymmetric total synthesis of norzoanthamine using radical reactions as key steps for rapid access to the congested carbocyclic core, which is the major synthetic challenge for most zoanthamine alkaloids. (1) The Ueno-Stork radical cyclization was applied to construct the adjacent quaternary centers at the C-9 and C-22 positions; (2) a Co-catalyzed HAT radical reaction was successfully applied to construct the quaternary center at C-12 via Csp -Csp bond formation; (3) a Mn-catalyzed HAT radical reaction was used to stereospecifically reduce the tetra-substituted olefin (C13=C18) and install the contiguous stereocenters in proximity to the quaternary center. A one-pot bio-inspired cyclization step was finally applied to forge the unstable bis-amino acetal skeleton. Our approach can precisely control the stereochemistry of seven vicinal stereocenters and effectively construct the highly congested heptacyclic skeleton.
我们在此报告使用自由基反应作为关键步骤的诺佐安他明的不对称全合成，这是大多数 zoanthamine 生物碱的主要合成挑战。（1）Ueno-Stork 自由基环化反应被应用于构建 C-9 和 C-22 位置的相邻季碳原子；（2）Co 催化的 HAT 自由基反应成功地应用于通过 Csp -Csp 键形成在 C-12 构建季碳原子；（3）Mn 催化的 HAT 自由基反应用于立体特异性还原四取代烯烃（C13=C18）并在靠近季碳原子的位置安装相邻的立体中心。最后，采用一锅法生物启发环化步骤形成不稳定的双氨基缩醛骨架。我们的方法可以精确控制七个相邻立体中心的立体化学，并有效地构建高度拥挤的七元环骨架。
