1668-85-5Relevant articles and documents
Total synthesis of (±)-galanthamine from GABA through regioselective aryne insertion
Venkatesh, Telugu,Mainkar, Prathama S.,Chandrasekhar, Srivari
, p. 2192 - 2198 (2019)
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.
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Bhandarkar,J.G.,Kirby,G.W.
, p. 1224 - 1227 (1970)
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Studies on the synthesis of heterocyclic compounds. CCCXV. Modified total synthesis of (plus or minus)-galanthamine through phenol oxidation.
Kametani,Yamaki,Yagi,Fukumoto
, p. 2602 - 2605 (1969)
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The application of a specific morphinan template to the synthesis of galanthamine
Yamamoto, Naoshi,Okada, Takahiro,Harada, Yukimasa,Kutsumura, Noriki,Imaide, Satomi,Saitoh, Tsuyoshi,Fujii, Hideaki,Nagase, Hiroshi
, p. 5751 - 5758 (2017/09/05)
(–)-Galanthamine (4) was synthesized from naltrexone (1) in 18 steps with 3% total yield by overcoming many specific side reactions derived from the 4,5-epoxymorphinan skeleton. The key features are cleavage of the D-ring by the Hofmann elimination and the following the one-pot C9–C10 and C9–14 bond cleavages concomitant with the C9 removal by the OsO4–NaIO4 combination reaction. Then, the treatment with zinc powder in acetic acid led to not only removal of the 2,2,2-trichloroethoxycarbonyl (Troc) group, but also reductive amination of the resulting imine to give the desired 7-membered ring.
Synthesis and evaluation of (-)- and (+)-[11C]galanthamine as PET tracers for cerebral acetylcholinesterase imaging
Kimura, Hiroyuki,Kawai, Tomoki,Hamashima, Yoshio,Kawashima, Hidekazu,Miura, Kenji,Nakaya, Yuta,Hirasawa, Makoto,Arimitsu, Kenji,Kajimoto, Tetsuya,Ohmomo, Yoshiro,Ono, Masahiro,Node, Manabu,Saji, Hideo
, p. 285 - 291 (2014/01/17)
Improved radiopharmaceuticals for imaging cerebral acetylcholinesterase (AChE) are needed for the diagnosis of Alzheimer's disease (AD). Thus, 11C-labeled (-)-galanthamine and its enantiomers were synthesized as novel agents for imaging the localization and activity of AChE by positron emission tomography (PET). C-11 was incorporated into (-)- and (+)-[ 11C]galanthamine by N-methylation of norgalanthamines with [ 11C]methyl triflate. Simple accumulation of 11C in the brain was measured in an in vivo biodistribution study using mice, whilst donepezil was used as a blocking agent in analogous in vivo blocking studies. In vitro autoradiography of rat brain tissue was performed to investigate the distribution of (-)-[11C]galanthamine, and confirmed the results of PET studies in mice. The radiochemical yields of N-methylation of (-)- and (+)-norgalanthamines were 13.7% and 14.4%, respectively. The highest level of accumulation of 11C in the brains of mice was observed at 10 min after administration (2.1% ID/g). Intravenous pretreatment with donepezil resulted in a 30% decrease in accumulation of (-)-[11C]galanthamine in the striatum; however, levels in the cerebellum were unchanged. In contrast, use of (+)-[11C]galanthamine led to accumulation of radioactivity in the striatum equal to that in the cerebellum, and these levels were unaffected by pretreatment with donepezil. In in vitro autoradiography of regional radioactive signals of brain sections showed that pretreatment with either (-)-galanthamine or donepezil blocked the binding of (-)-[11C] galanthamine to the striatum, while sagittal PET imaging revealed accumulation of (-)-[11C]galanthamine in the brain. These results indicate that (-)-[11C]galanthamine showed specific binding to AChE, whereas (+)-[11C]-galanthamine accumulated in brain tissue by non-specific binding. Thus, optically pure (-)-[11C]galanthamine could be a useful PET tracer for imaging cerebral AChE.
