RESUMO
An asymmetric synthetic route to (-)-galanthamine (1), a pharmacologically active Amaryllidaceae alkaloid used for the symptomatic treatment of early onset Alzheimer's disease, was successfully established with very high levels of stereocontrol. The key to achieving high chemo- and stereo-selectivity in this approach was the use of transition-metal-mediated reactions, namely, enyne ring-closing metathesis, Heck coupling, and titanium-based asymmetric allylation.
Assuntos
Alcaloides , Doença de Alzheimer , Galantamina , HumanosRESUMO
Short routes to enantiomerically pure indolizidine and quinolizidine alkaloids have been developed using imino-aldol reactions of enolates derived from phenyl 5-chlorovalerate. High levels of syn selectivity (dr â¼13-16:1) were obtained using lithium enolates of phenyl esters in combination with tert-butylsulfinyl imines. The imino-aldol adducts were deprotected and cyclized to afford (-)-epilupinine ((-)-2) and (-)-tashiromine ((-)-1) in two further steps.
Assuntos
Aldeídos/química , Iminas/química , Indolizinas/síntese química , Esparteína/análogos & derivados , Ciclização , Estrutura Molecular , Esparteína/síntese químicaRESUMO
[reaction: see text] Ring-closing metathesis (RCM) of vinyl fluoride-containing dienes in the presence of ruthenium alkylidene carbene complex 11 proceeded efficiently to give six- and seven-membered cyclic vinyl fluorides. The RCM reaction was used to prepare amine- and sulfamide-linked cyclo-olefins, as well as carbocyclic systems, from a simple commercial fluoro-olefin.