1668-86-6Relevant articles and documents
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)
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.
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.
Thiol-Reactive Analogues of Galanthamine, Codeine, and Morphine as Potential Probes to Interrogate Allosteric Binding within Nicotinic Acetylcholine Receptors
Gallagher, Ryan,Chebib, Mary,Balle, Thomas,McLeod, Malcolm D.
, p. 1834 - 1841 (2015/12/26)
Alkaloids including galanthamine (1) and codeine (2) are reported to be positive allosteric modulators of nicotinic acetylcholine receptors (nAChRs), but the binding sites responsible for this activity are not known with certainty. Analogues of galanthamine (1), codeine (2), and morphine (3) with reactivity towards cysteine thiols were synthesized including conjugated enone derivatives of the three alkaloids 4-6 and two chloro-alkane derivatives of codeine 7 and 8. The stability of the enones was deemed sufficient for use in buffered aqueous solutions, and their reactivity towards thiols was assessed by determining the kinetics of reaction with a cysteine derivative. All three enone derivatives were of sufficient reactivity and stability to be used in covalent trapping, an extension of the substituted cysteine accessibility method, to elucidate the allosteric binding sites of galanthamine and codeine at nAChRs.
Stereoselective syntheses of galanthamine and its stereoisomers by complementary Luche and L-selectride reductions
Trinadhachari, Ganala Naga,Kamat, Anand Gopalkrishna,Raghu Babu, Korupolu,Sanasi, Paul Douglas,Prabahar, Koilpillai Joseph
, p. 117 - 124 (2014/02/14)
A diastereodivergent approach for the stereoselective syntheses of all four stereoisomers of galanthamine, (-)-galanthamine 1, (+)-galanthamine 2, (-)-epigalanthamine 3, and (+)-epigalanthamine 4, from (±)-narwedine 5 is reported. Thus (±)-narwedine 5 was resolved by dynamic kinetic resolution to obtain enantiomerically pure (-)-narwedine 6 and (+)-narwedine 7. Each enantiomerically pure isomer of narwedine was subjected to Luche and L-selectride reactions to obtain all four isomers of galanthamine. In these reactions, the (-)-galanthamine 1 and (+)-galanthamine 2 isomers were obtained with an enantiomeric purity of >99.5%, whereas (-)-epigalanthamine 3 and (+)-epigalanthamine 4 are obtained with a chiral purity of >97%. The axial hydride attack by the Luche reduction and the equatorial hydride attack by the L-selectride reduction on the cyclic enone system are explored in the stereoselective synthesis of the galanthamine isomers and thus it was demonstrated that the stereoselective synthesis involving the Luche and L-selectride reductions are complementary in yielding enantiomeric stereogenic centers from a prochiral carbonyl group on the cyclic enone system.
Commercial scale process of galanthamine hydrobromide involving Luche reduction: Galanthamine process involving regioselective 1,2-reduction of α,β-unsaturated ketone
Trinadhachari, Ganala Naga,Kamat, Anand Gopalkrishna,Prabahar, Koilpillai Joseph,Handa, Vijay Kumar,Srinu, Kukunuri Naga Venkata Satya,Babu, Korupolu Raghu,Sanasi, Paul Douglas
, p. 406 - 412 (2013/06/05)
Effect of lanthanide chloride in the Luche regioselective 1,2-reduction of 1-bromo-11-formyl-nornarwedine (5) was studied. Thus, 1-bromo-11-formyl- nornarwedine (5) is reduced with sodium borohydride in the presence of lanthanide chloride to yield 1-bromo-11-formyl-galanthamine isomers (6), which is a key intermediate for the commercial production of highly pure galanthamine hydrobromide (1), a modern drug against Alzheimer's disease.
Total synthesis of (±)-Galanthamine via a C3-selective stille coupling and IMDA cycloaddition cascade of 3,5-dibromo-2-pyrone
Chang, Jay Hyok,Kang, Ho-Ung,Jung, In-Hak,Cho, Cheon-Gyu
supporting information; experimental part, p. 2016 - 2018 (2010/06/21)
Figure presented A new efficient synthetic route to (±)-galanthamine was devised by using a tandem C3-selective Stille coupling-IMDA cascade of 3,5-dibromo-2-pyrone as a key strategy.
SYNTHESIS OF MORPHINE AND RELATED DERIVATIVES
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Page/Page column 86-87, (2010/12/17)
The present invention relates to methods for the synthesis of galanthamine, morphine, intermediates, salts and derivatives thereof, wherein the starting compound is biphenyl.
Concise syntheses of (-)-galanthamine and (±)-codeine via intramolecular alkylation of a phenol derivative
Magnus, Philip,Sane, Neeraj,Fauber, Benjamin P.,Lynch, Vince
supporting information; experimental part, p. 16045 - 16047 (2010/02/16)
(Figure Presented). A new solution-processable fabrication protocol using a soluble tetrabenzoporphyrin (BP) precursor and bis(dimethylphenylsilylmethyl) [60]fullerene (SIMEF) created three-layered p-i-n photovoltaic devices, in which the i-layer possesses a well-defined bulk heterojunction structure in which columnar BP crystals grow vertically from the bottom p-layer. The device showed a power conversion efficiency of 5.2% (VOC = 0.75 V; JSC = 10.5 mA/cm2; FF = 0.65).
An improved process for the preparation of galantamine hydrobromide
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Page/Page column 10; 11, (2009/01/24)
The present invention relates to an improved process for the preparation of [4aS,6R,8aS]-4a,5,9,10,11,12-hexahydro-3-methoxy-11-methyl-6H-benzofuro[3a,3,2-ef][2]benzazepin-6-ol of Formula I
