Kopsinitarine E, an indole alkaloid with a highly strained cage system, is synthesized for the first time in 20 steps. The fused‐ring system was efficiently installed by an unprecedented SmI2‐mediated Dieckmann‐like condensation, Prins‐type cyclization cascade, and subsequent semi‐pinacol rearrangement. Boc=tert‐butoxycarbonyl; TES=triethylsilyl.
Kopsinitarines A–E are complex octacyclic caged Kopsia alkaloids with strained cage skeletons and a unique cyclic hemiaminal bridge that makes total synthesis challenging. Herein, we disclose the first total synthesis of kopsinitarine E. The key synthetic features include a SmI2‐mediated radical cascade cyclization and a subsequent semi‐pinacol rearrangement to install the key carbocyclic skeleton, a chemoselective hydrosilyl amide reduction to construct the hemiaminal ether bridge, and an intramolecular Mannich reaction to establish the highly strained cage system.
Wiley: Angewandte Chemie International Edition: Table of Contents
Authors: Karre Nagaraju, Dongshun Ni, Dawei Ma