Asymmetric Total Synthesis of Norzoanthamine

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(3)-Csp(2) 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.

Automated summary

The asymmetric total synthesis of norzoanthamine was achieved using radical reactions as key steps. This approach allowed for precise control of stereochemistry and construction of the highly congested heptacyclic skeleton, addressing a major synthetic challenge in most zoanthamine alkaloids.