Total Synthesis of Kopsinitarine E

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 cas...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2020-12, Vol.59 (49), p.22039-22042
Main Authors: Nagaraju, Karre, Ni, Dongshun, Ma, Dawei
Format: Article
Language:English
Subjects:
Alkaloids
Apocynaceae - chemistry
Cages
cyclization
indole alkaloids
Mannich reaction
Molecular Structure
semi-pinacol rearrangement
Synthesis
total synthesis
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Summary: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. 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.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202011093