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A Novel Synthesis of (−)-Huperzine A via Tandem Intramolecular Aza-Prins Cyclization–Cyclobutane Fragmentation

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posted on 2013-02-15, 00:00 authored by James D. White, Yang Li, Jungchul Kim, Miroslav Terinek
The acetylcholinesterase inhibitor (−)-huperzine A was synthesized from (S)-4-hydroxycyclohex-2-enone in 17 steps by a route that involved two cyclobutane fragmentations. The first of these employed a retro-aldol cleavage to generate the α-pyridone ring of huperzine A, and the second invoked a novel intramolecular aza-Prins reaction in tandem with stereocontrolled scission of a cyclobutylcarbinyl cation to create the aminobicyclo[3.3.1]nonene framework of the natural alkaloid.

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