Calyciphylline B‑type Alkaloids: Evolution of a Synthetic Strategy to (−)-Daphlongamine H

We provide a full account of our synthetic studies targeting the hexacyclic calyciphylline B-type alkaloids, a subfamily of the Daphniphyllum natural products. Following an initial set of synthetic strategies focused on constructing the piperidine core of the calyciphylline B-type framework via a 6π-azaelectrocyclization, as well as exploiting the reactivity of underexplored oxazaborinine heterocycles, we ultimately designed a highly functionalized acyclic precursor which underwent carefully orchestrated and efficient cyclizations to forge the architecturally complex natural product scaffold. Our efforts have culminated in the development of the first total synthesis of (−)-daphlongamine H, provided access to its C5-epimer, (−)-isodaphlongamine H, and led to structural revision of deoxyisocalyciphylline B.