- Electrochemical: N -demethylation of tropane alkaloids
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A practical, efficient, and selective electrochemical N-demethylation method of tropane alkaloids to their nortropane derivatives is described. Nortropanes, such as noratropine and norscopolamine, are important intermediates for the semi-synthesis of the medicines ipratropium or oxitropium bromide, respectively. Synthesis was performed in a simple home-made electrochemical batch cell using a porous glassy carbon electrode. The reaction proceeds at room temperature in one step in a mixture of ethanol or methanol and water. The method avoids hazardous oxidizing agents such as H2O2 or m-chloroperbenzoic acid (m-CPBA), toxic solvents such as chloroform, as well as metal-based catalysts. Various key parameters were investigated in electrochemical batch or flow cells, and the optimized conditions were used in batch and flow-cells at gram scale to synthesize noratropine in high yield and purity using a convenient liquid-liquid extraction method without any need for chromatographic purification. Mechanistic studies showed that the electrochemical N-demethylation proceeds by the formation of an iminium intermediate which is converted by water as the nucleophile. The optimized method was further applied to scopolamine, cocaine, benzatropine, homatropine and tropacocaine, showing that this is a generic way of N-demethylating tropane alkaloids to synthesize valuable precursors for pharmaceutical products.
- Alipour Najmi, Ali,Bischoff, Rainer,Dekker, Frank J.,Permentier, Hjalmar P.,Xiao, Zhangping
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p. 6455 - 6463
(2020/11/09)
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- Utility of iron nanoparticles and a solution-phase iron species for the: N-demethylation of alkaloids
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The N-demethylation of selected N-methylalkaloids using a modified Polonovski reaction can be accomplished using a novel green methodology employing nanoscale zero-valent iron, nZVI, in isopropanol. Use of nZVI promotes a much faster conversion to N-demethylated products due to much higher surface area on the metal surface as shown by SEM analysis. Rates of conversion can be further enhanced using catalytic quantities of the solubilised iron(0) species triiron dodecacarbonyl, Fe3(CO)12.
- Awalt, Jon Kyle,Lam, Raymond,Kellam, Barrie,Graham, Bim,Scammells, Peter J.,Singer, Robert D.
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p. 2587 - 2594
(2017/07/17)
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- CHROMEN-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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The present applications discloses novel 8-aza-bicyclo[3.2.1]oct-3-yloxy)-chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors. In other aspects the applications discloses the use of these compounds in a method for th
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Page/Page column 14
(2012/01/14)
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- NOVEL COMPOUNDS
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The present applications discloses novel 8-aza-bicyclo[3.2.1]oct-3-yloxy)chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors. In other aspects the applications discloses the use of these compounds in a method for the
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Page/Page column 6
(2012/01/14)
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- Structure-based design, synthesis and structure-activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein
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Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the α7 and α4β2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes.
- Edink, Ewald,Akdemir, Atilla,Jansen, Chimed,Elk, René Van,Zuiderveld, Obbe,De Kanter, Frans J.J.,Van Muijlwijk-Koezen, Jacqueline E.,Smit, August B.,Leurs, Rob,De Esch, Iwan J.P.
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p. 1448 - 1454
(2012/04/04)
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- CHROMEN-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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The present application discloses novel 8-aza-bicyclo[3.2.1]oct-3-yloxy)-chromen- 2-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the application discloses the use of these compounds, a method for therapy and to pharmaceutical compositions comprising these compounds.
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- CHROMEN-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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The present applications discloses novel 8-aza-bicyclo[3.2.1]oct-3-yloxy)- chromen-2-one derivatives and their use as monoamine neurotransmitter re-uptake inhibitors. In other aspects the applications discloses the use of these compounds in a method for t
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Page/Page column 13-14
(2010/12/17)
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- NOVEL BENZOOXAZOL- AND BENZOOXATHIOL-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel benzooxazol- and benzooxathiol-2-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 11
(2009/04/25)
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- NOVEL PHENOXAZIN-3-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel phenoxazin-3-one derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 10
(2009/04/25)
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- NOVEL CHROMEN-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel chromen-2-one derivatives of Formula (I) useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical composit
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Page/Page column 14
(2008/12/06)
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- NOVEL CHROMEN-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel chromen-2-one derivatives of Formula (I) useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical composit
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Page/Page column 14-15
(2008/12/06)
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- 8-AZA-BICYCLO[3.2.1]OCTANE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel 8-aza-bicyclo[3.2.1]octane derivatives useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.
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Page/Page column 13
(2008/06/13)
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- NOVEL CHROMEN-2-ONE DERIVATIVES AND THEIR USE AS MONOAMINE NEUROTRANSMITTER RE-UPTAKE INHIBITORS
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This invention relates to novel chromen-2-one derivatives of formula (I) useful as monoamine neurotransmitter re-uptake inhibitors. In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention. Formula (I) wherein Q represents a chromen-2-one group; which chromen-2-one group is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; R1 represents hydrogen or alkyl; which alkyl is optionally substituted with one or more substituents independently selected from the group consisting of: halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxy, amino, nitro, alkoxy, cycloalkoxy, alkyl, cycloalkyl, cycloalkylalkyl, alkenyl and alkynyl; and R2 and R3 together form -(CH2)-(CH2)- or -(CH)=(CH)-.
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Page/Page column 14
(2008/06/13)
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- Further investigation of the N-demethylation of tertiary amine alkaloids using the non-classical Polonovski reaction
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The iron salt-mediated Polonovski reaction efficiently N-demethylates certain opiate alkaloids. In this process, the use of the hydrochloride salt of the tertiary N-methyl amine oxide was reported to give better yields of the desired N-demethylated product. Herein, we report further investigation into the use of N-oxide salts in the iron salt-mediated Polonovski reaction. An efficient approach for the removal of iron salts that greatly facilitates isolation and purification of the N-nor product is also described.
- Thavaneswaran, Shanti,Scammells, Peter J.
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p. 2868 - 2871
(2007/10/03)
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- Synthesis of tropeines and allosteric modulation of ionotropic glycine receptors
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Twenty esters of 3α- and 3β-hydroxy(nor)tropanes and two amides of 3α-aminotropane were prepared with substituted benzoic acids. These (nor)tropeines inhibited [3H]strychnine binding to glycine receptors in synaptosomal membranes of rat spinal cord. A ternary allosteric model was applied to determine the dissociation constants (KA) of the tropeines having strong negative cooperativities with [3H]strychnine binding (α > 10). KA values about 10 nM are well below those of known allosteric agents. Low concentrations (0.1KA) of the (nor)tropeines potentiated the displacing effects of glycine. Positive cooperativity with glycine (β1) decreased with the increase in concentration and binding affinity of tropeines. Displacing potencies were also measured for [3H]granisetron binding to 5-HT3 type serotonin receptors of rat cerebral cortex. Selectivities to glycine receptors versus 5-HT3 receptors varied within 4 orders of magnitude. Nortropeines might serve as a lead to high-affinity selective allosteric modulators of glycine receptors.
- Maksay, Gabor,Nemes, Péter,Biró, Tímea
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p. 6384 - 6391
(2007/10/03)
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- ALKALOIDS OF SOME SOUTH AMERICAN ERYTHROXYLUM SPECIES
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Erythroxylum; Erythroxylaceae; chemotaxonomy; tropane alkaloids; cuscohygrine; nortropacocaine.Fourteen South American species of Erythroxylum representing four sections of the genus were examined for tropane and related alkaloids.The alkaloid content of
- El-Imam, Y. M. A.,Evans, W. C.,Plowman, T.
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p. 2285 - 2290
(2007/10/02)
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- A NEW SYNTHETIC ROUTE TO TROPANE ALKALOIDS. PSEUDOTROPINE AND TROPACOCAINE
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Pseudotropine and tropacocaine have been synthesized by a facile route involving the nitroso cycloaddition followed by internal SN2 displacement.
- Iida, Hideo,Watanabe, Yohya,Kibayashi, Chihiro
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p. 5091 - 5094
(2007/10/02)
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