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.