7318-55-0Relevant articles and documents
Total synthesis of (±)-galanthamine from GABA through regioselective aryne insertion
Venkatesh, Telugu,Mainkar, Prathama S.,Chandrasekhar, Srivari
, p. 2192 - 2198 (2019/02/27)
The total synthesis of (±)-galanthamine is achieved in ～5% overall yield using a key regioselective aryne insertion reaction into a GABA (γ-amino butyric acid) derivative. The strategy presented involves only two sub-critical temperature reactions and less than five chromatographic purifications to achieve the synthesis of galanthamine.
An Eleven-Step Synthesis of Galanthamine from Commercially Available Materials
Nugent, Jeremy,Banwell, Martin G.
, p. 5862 - 5867 (2016/12/18)
Narwedine, an immediate precursor to the therapeutically valuable alkaloid (–)-galanthamine, has been synthesised by engaging an iodinated isovanillin derivative in an intermolecular Mitsunobu reaction with a 2-cyclohexen-1-ol derivative. The resulting aryl ether participated in an exceptionally efficient intramolecular Heck reaction to give a tetracyclic lactol after the hydrolysis of the primary cyclisation product. This last compound is an advanced intermediate associated with the Magnus synthesis of narwedine and could be elaborated to narwedine itself under reductive amination conditions. As a result, an eleven-step synthesis of galanthamine has been established.
A total synthesis of galanthamine involving de novo construction of the aromatic C-ring
Nugent, Jeremy,Matou?ová, Eli?ka,Banwell, Martin G.
, p. 3771 - 3778 (2015/06/16)
The tetracyclic alkaloid galanthamine is used clinically in a number of countries for the symptomatic treatment of mild to moderate forms of Alzheimer's disease, and this feature coupled with its novel molecular architecture has prompted an extensive focus on its synthesis. The present study reports a new and distinct synthesis of galanthamine wherein the AB-ring substructure and associated quaternary carbon centre are constructed by using a palladium-catalyzed intramolecular Alder-ene reaction. The product of this process is engaged in a Tsuji-Trost-type reaction to generate a semicyclic diene that participates in a normal-electron-demand Diels-Alder reaction to generate, after oxidation of the initially formed adduct, the aromatic C-ring of the target alkaloid. Modified Bischler-Napieralski chemistry is then deployed to construct the seven-membered D-ring and thereby furnishing narwedine, an established precursor to both (+)- and (-)-galanthamine. The first synthesis of the alkaloid galanthamine is reported in which the aromatic C-ring is assembled from non-aromatic precursors. This was accomplished by a Diels-Alder cycloaddition reaction. The diene used embodies the AB-ring system (and associated quaternary carbon centre) and was constructed by intramolecular Alder-ene and Tsuji-Trost-type chemistries. The D-ring was closed by a modified Bischler-Napieralski reaction.
