Concise Synthesis of Norzoanthamine Enabled by a Set of Photochemical Transformations

Click to copy article linkArticle link copied!

Norzoanthamine is a structurally complex polycyclic natural product that expresses a broad range of biological activities, rendering facile access to it and its analogs of considerable importance in drug discovery and development. However, strategies for efficient access to this class of marine alkaloids remain lacking. Here, we report a strategy, characterized by three key photochemical reactions, that we used to synthesize norzoanthamine in 16 steps. A photoinduced dearomative-6π-desymmetrization was developed for facile access to the ABC-tricyclic core of the alkaloid. This was supplemented by a [2 + 2]-photocycloaddition, a visible-light-induced decarboxylative borylation, and a retro-aldol process, constituting an effective solution to the challenging problem of establishing the C9–C22 vicinal all-carbon quaternary stereogenic centers. Finally, a one-pot cascade transformation, involving global deprotection, cyclization, and epimerization reaction, was designed for efficient and stereocontrolled assembly of the core framework of norzoanthamine.