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.