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.

本研究完整报道了针对六环型牛耳枫碱B类生物碱（hexacyclic calyciphylline B-type alkaloids）的全合成研究工作，该类生物碱是虎皮楠属（Daphniphyllum）天然产物的一个亚家族。在初期的合成策略研究中，我们曾尝试通过6π-氮杂电环化反应（6π-azaelectrocyclization）构建牛耳枫碱B型骨架的哌啶（piperidine）核心，并探索了尚未被充分研究的氧杂硼氮杂环（oxazaborinine）的反应活性；最终我们设计了一种高官能团化的非环前体，该前体经过精心调控的高效环化反应，构筑了结构复杂的天然产物骨架。本研究最终实现了(−)-长序虎皮楠碱H（(−)-daphlongamine H）的首例全合成，获得了其C5差向异构体(−)-异长序虎皮楠碱H（(−)-isodaphlongamine H），并修正了deoxyisocalyciphylline B的化学结构。