Calyciphylline B‑Type Alkaloids: Total Syntheses of (−)-Daphlongamine H and (−)-Isodaphlongamine H

The first total synthesis of the complex hexacylic Daphniphyllum alkaloid (−)-daphlongamine H has been accomplished. Key to the success of the strategy are a complexity-building Mannich reaction, efficient cyclizations, and a highly diastereoselective hydrogenation to assemble multigram quantities of the tricyclic core bearing four contiguous stereocenters. Following construction of the hydro-indene substructure by means of a Pauson–Khand reaction, endgame redox manipulations delivered the natural product. Importantly, the synthetic studies have also given access to (−)-isodaphlongamine H and led to a revision of the reported structure of deoxyisocalyciphylline B.