Enantioselective Total Synthesis of (−)-Verarine via Late-Stage Bond Ablation

The selective cleavage of C–N bonds in complex molecules offers a powerful strategy for accessing new chemical space. Described herein is an enantioselective total synthesis of (−)-verarine that combines a highly efficient [2 + 2 + 2] cycloisomerization, which constructs three rings of the contiguous hexacyclic cevanine skeleton in a single operation, with a late-stage regioselective ablation of a benzylic C–N bond to unveil the veratramine framework. This precise reorganization of a densely functionalized Veratrum scaffold provides a concise total synthesis of (−)-verarine and should enable access to other members of this family.