Total synthesis of kopsinitarine E

Kopsinitarines A-E are complex octacyclic caged kopsia alkaloids, whose strained cage skeleton and the unique cyclic hemiaminal bridge make them challenging for the total synthesis. Herein, we disclose the first total synthesis of kopsinitarine E. The key synthetic features include a SmI 2 -mediated radical cascade cyclization and a subsequent semi-pinacol rearrangement to install its key carbocyclic skeleton, a chemoselective hydrosilyl amide reduction to build up its hemiaminal ether bridge, and an intramolecular Mannich reaction to establish its highly strained cage system.