A novel synthesis of (-)-huperzine A via tandem intramolecular aza-Prins cyclization-cyclobutane fragmentation.
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.
Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, United States. james.white@oregonstate.edu
James D
JD
White
Yang
Y
Li
Jungchul
J
Kim
Miroslav
M
Terinek
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D003503:Cyclobutanes / Q000737:chemistry*; D015394:Molecular Structure; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D003503:Cyclobutanes; D012717:Sesquiterpenes; C050426:huperzine A