- Kinetics of oxidation of atropine by alkaline KMnO4 in aqueous solutions
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Kinetics of oxidation of atropine by alkaline KMnO4 has been studied in aqueous solutions at various temperatures. Kinetic I measurements were performed at constant pH and constant ionic strength, under pseudo-first order condition in which the concentration i of atropine was around an order of magnitude greater than that of KMnO4. The observed rate constant was obtained by following the change in absorbance of the reaction mixture with time at a predetermined wavelength. The overall rate constant and the orders of the I reaction with respect to concentrations of both atropine and KMnO4 were determined. Two observed rates and hence, two rates constant | were found. This indicates that the oxidation process occurs in two steps with the formation of intermediates. A suggested mechanism for I the reaction is given which agrees with kinetics results. The activation energy of the process was convoluted from temperature effect on. the rate of the reaction.
- Saleh, Abdullah I.,Al-Ghreizat, Sanad K.,Abdel-Halim, Hamzeh M.
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- Difficulties in Differentiating Natural from Synthetic Alkaloids by Isotope Ratio Monitoring using 13 C Nuclear Magnetic Resonance Spectrometry
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Within the food and pharmaceutical industries, there is an increasing legislative requirement for the accurate labeling of the product's origin. A key feature of this is to indicate whether the product is of natural or synthetic origin. With reference to
- Robins, Richard J.,Romek, Katarzyna M.,Grand, Mathilde,Nun, Pierrick,Diomande, Didier,Julien, Maxime,Remaud, Gérald S.
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- The synthesis and separation of [3-2H]tropine and [3-2H]pseudotropine (Ψ-tropine)
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Tropine was reduced using sodium borodeuteride to give a mixture of the epimers [3-2H]tropine and [3-2H]pseudotropine with the latter compound predominating and constituting about 70% of the mixture. Crystallisation of the product from diethyl ether gave crystals of pure [3-2H]pseudotropine and a supernatant solution containing a mixture of the epimers. Acetylation of this mixture using acetyl chloride preferentially acetylated the pseudotropine and the acetylated products were separated from the tropine by flash chromatography to leave a sample of pure [3-2H]tropine.
- Bartholomew,Smith,Darcy,Trudgill,Hopper
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- CRYSTALLINE ATROPINE SULFATE
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The present invention relates to crystalline polymorph form of Atropine sulfate and process for the preparation thereof.
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Page/Page column 4-5
(2014/07/21)
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- Spectroscopic investigation and oxidation of the anticholinergic drug atropine sulfate monohydrate by hexacyanoferrate(III) in aqueous alkaline media: A mechanistic approach
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The oxidation of the anticholinergic drug atropine sulfate monohydrate by hexacyanoferrate(III) in aqueous alkaline media was investigated spectrophotometrically by monitoring the decrease in absorbance of hexacyanoferrate(III) (HCF(III)). Oxidation products were identied. The oxidation mechanism was proposed from kinetic studies. The reaction constants involved in the dierent steps of the mechanism were calculated. The eects of added products, ionic strength, and dielectric constant of the reaction were investigated. The polymerization test revealed that oxidation occurred with intervention of free radicals. The activation parameters were evaluated. TUeBITAK.
- Meti, Manjunath,Nandibewoor, Sharanappa,Chimatadar, Shivamurti
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p. 477 - 487
(2014/06/09)
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- Spectroscopic investigation and reactivities of ruthenium(iii) catalyzed oxidation of anticholinergic drug atropine sulfate monohydrate by hexacyanoferrate(iii) in aqueous alkaline media: A mechanistic approach
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The kinetics of oxidation of an atropine sulfate monohydrate (ASM) by hexacyanoferrate (HCF) (III) has been investigated spectrophotometrically in presence of ruthenium(III) catalyst in aqueous alkaline medium at 25°C. The stoichiometry is 1: 2. The reaction is first order in HCF(III) and has less than unit order in ASM concentrations. The effect of ionic strength and dielectric constants were studied on the rate of reaction. The active species of oxidant and catalyst are Fe(CN)63- and [Ru(H2O)5(OH)]2+, respectively. A suitable mechanism is proposed. The catalytic constant (KC) was also calculated. The activation parameters and thermodynamic quantities are also determined and discussed.
- Meti, Manjunath D.,Nandibewoor, Sharanappa T.,Chimatadar, Shivamurti A.
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p. 263 - 272
(2013/11/19)
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- Catalytic activity of ruthenium(III) on the oxidation of an anticholinergic drug-atropine sulfate monohydrate by copper(III) periodate complex in aqueous alkaline medium - Decarboxylation and free radical mechanism
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Atropine sulfate monohydrate (ASM) is an anticholinergic drug, having a wide spectrum of activity. Hence, the kinetics of oxidation of ASM by diperiodatocuperate (DPC) in the presence of micro (10-6) amounts of Ru(III) catalyst has been investigated spectrophotometrically in aqueous alkaline medium at I = 0.50 mol dm-3. The reaction between DPC and ASM exhibits 1:2 stoichiometry (ASM:DPC) i. e., one mole of ASM require two moles of DPC to give products. The main oxidation products were confirmed by spectral studies. The reaction is first order with respect to [DPC] and [Ru(III)], while the order with respect to [ASM] and [OH-] was less than unity. The rates decreased with increase in periodate concentration. The reaction rates revealed that Ru(III) catalyzed reaction was about seven-fold faster than the uncatalyzed reaction. The catalytic constant (KC) was also determined at different temperatures. A plausible mechanism is proposed. The activation parameters with respect to slow step of the mechanism were calculated and the thermodynamic quantities were also determined. Kinetic experiments suggest that [Cu(H 2IO6)(H2O)2] is the reactive Cu(III) species and [Ru(H2O)5OH]2+ is the reactive Ru(III) species.
- Byadagi, Kirthi S.,Nandibewoor, Sharanappa T.,Chimatadar, Shivamurti A.
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p. 617 - 627
(2013/09/23)
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- A METHOD FOR THE N-DEMETHYLATION OF N-METHYL HETEROCYCLES
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The present invention provides methods of N-demethylating, N-methylated heterocycles and N-methyl, N-oxide heterocycles using a transition metal with an oxidation state of zero, ferrocene or substituted derivatives thereof, or Cr 3+ .N-demethylated heterocycles prepared by the methods of the present invention are also provided.
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Page/Page column 42
(2011/04/19)
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- N-Demethylation of N-methyl alkaloids with ferrocene
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Under Polonovski-type conditions, ferrocene has been found to be a convenient and efficient catalyst for the N-demethylation of a number of N-methyl alkaloids such as opiates and tropanes. By judicious choice of solvent, good yields have been obtained for dextromethorphan, codeine methyl ether, and thebaine. The current methodology is also successful for the N-demethylation of morphine, oripavine, and tropane alkaloids, producing the corresponding N-nor compounds in reasonable yields. Key pharmaceutical intermediates such oxycodone and oxymorphone are also readily N-demethylated using this approach.
- Kok, Gaik B.,Scammells, Peter J.
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supporting information; experimental part
p. 4499 - 4502
(2010/09/15)
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- Specificities of the enzymes of N-alkyltropane biosynthesis in Brugmansia and Datura
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The enzymes N-methylputrescine oxidase (MPO), the tropine-forming tropinone reductase (TRI), the pseudotropine-forming tropinone reductase (TRII), the tropine:acyl-CoA transferase (TAT) and the pseudotropine:acyl-CoA transferase (PAT) extracted from transformed root cultures of Datura stramonium and a Brugmansia candida x aurea hybrid were tested for their ability to accept a range of alternative substrates. MPO activity was tested with N-alkylputrescines and N-alkylcadaverines as substrates. TRI and TRII reduction was tested against a series of N-alkylnortropinones, N- alkylnorpelletierines and structurally related ketones as substrates. TAT and PAT esterification tests used a series of N-substituted tropines, pseudotropines, pelletierinols and pseudopelletierinols as substrates to assess the formation of their respective acetyl and tigloyl esters. The results generally show that these enzymes will accept alien substrates to varying degrees. Such studies may shed some light on the overall topology of the active sites of the enzymes concerned.
- Boswell, Henry D.,Draì?ger, Birgit,McLauchlan, W. Russell,Portsteffen, Andreas,Robins, David J.,Robins, Richard J.,Walton, Nicholas J.
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p. 871 - 878
(2007/10/03)
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- Detection and identification of side reactions of halogenated hydrocarbon solvents with amines of pharmaceutical interest by secondary processes to the neutralizations of sulphonphthaleinic dyes with these amines
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The neutralization reactions between amines and diprotic acid dyes in organic solvents generate {dye-, amineH+} and {dye2-, (amineH+)2} ion associates that show two absorption bands in the visible spectrum. An unidentified third absorption band; which appears with a high amine concentration, proves that halogenated hydrocarbon solvents (dichloromethane, chloroform, 1,2-dichloroethane, and carbon tetrachloride) give side reactions with amines (atropine, tropine, quinine, ephedrine, and ajmaline) that generate a quaternary ammonium salt, N-halogenalkylammonium halide ({N+- RX,X-}). The molecular weight of the quaternary ammonium salt is the sum of the amine and that of the solvent. The {N+-RX,X-} ion associated reacts with {dye2-, (amineH+)2} by substitution reactions, forming {dye2-, amineH+, N+-RX} and {dye2-, (N+-RX)2} ion associates that justify the third absorption band. The amine-solvent side reactions are of first order with respect to the amine, being very slow processes with rate constant values from 399.4 h-1 (tropine-dichloromethane reaction) to 15.8 h-1 (atropine-1,2-dichloroethane reaction). Rate constants increase with the basicity of the amine measured in the halogenated hydrocarbons employed. Rate constants also increase with a reduction in the number of the halogen atoms present in the halogenated solvent. The new visible absorption band that appears in the amine-dye neutralization gives a quick colorimetric test to bring to light this kind of side reaction in these solvents.
- Gainza,Konyeaso,Asenjo
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p. 226 - 232
(2007/10/02)
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- Feeding Experiments with Precursors of Tropane Alkaloids Using Suspension Cultures of Atropa belladonna
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Feeding experiments have been carried out with alkaloid precursors (hydrine, tropinone and tropic acid) using suspension cultures of Atropa belladonna to study the transport of these compounds into the cells, simulation of alkaloid synthesis, and possible repressed steps in their biosynthesis.Both hydrine and tropinone are transported into the cells and the turnover of hydrine is very high.The turnover rate of tropinone is considerably enhanced in cultures fed with both compounds simultaneously, but tropanol, hyoscyamine and scopolamine were consistently undetected in the cell material.Biosynthesis of precursors and alkaloids was repressed in the cultures studied, and the repressiion could not be reversed by increased intracellular substrate levels.
- Simola, Liisa Kaarina,Martinsen, Aarne,Huhtikangas, Aarre,Jokela, Reija,Lounasmaa, Mauri
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p. 702 - 705
(2007/10/02)
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- STEREOCONTROLLED SYNTHESIS OF TROPANOL DERIVATIVES VIA PALLADIUM-CATALYZED REACTIONS
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A general method for the transformation of 1,3-cycloheptadienes to tropane alkaloid derivatives was developed.The procedure was applied to the stereocontrolled synthesis of the exo- and endo-tropanol derivatives 1 and 2.The approach is based on a dual stereocontrol in the 1,4-functionalization of conjugated dienes.
- Baeckvall, J. E.,Renko, Z. D.,Bystroem, S. E.
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p. 4199 - 4202
(2007/10/02)
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- Conveniant Method for Replacement of Tertiary N-Methyl by Other Alkyl Groups: Application to Morphine Alkaloids
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The replacement of N-methyl of N-methylpiperidine (1), 4-methylmorpholine (4), 2-methyl-1,2,3,4-tetrahydroisoquinoline (7) and tropine (10) by n-propyl, n-butyl and isopropyl groups (3a-3c, 6c, 9a-9c and 12a-12c) has been achieved in high yields by quaternization of the respective tertiary amine with appropriate alkyl halide and demethylation of the resulting quaternary salt with thiophenoxide.It has been established that demethylation is strongly favoured over the removal of n-propyl and n-butyl groups, whereas deisopropylation occurs to some extent.Surprisingly, in the case of 11c, deisopropylation predominates.This method has been applied to morphine (13b), codeine (13d) and thebaine (14b) for similar replacements.The rapid quaternization of thebaine (14b) has been assigned to the absence of H-14 in this alkaloid.The fact that quaternary salts of thebaine, which are susceptible to aromatization of the nucleus by extrusion of the ethanamine chain, are smoothly demethylated to N-alkylnorthebaines (18a-18c) in good yields indicates that demethylation, a bimolecular nucleophilic displacement, competes very successfully with elimination reaction.
- Manoharan, T. Samuel,Madyastha, K. Madhava,Singh, B. B.,Bhatnagar, S. P.,Weiss, Ulrich
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- SUBSTITUTED THIENOBENZODIAZEPINONES AND SALTS THEREOF
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Compounds of the formula STR1 wherein R is 1-methyl-4-piperididinyl, 4-methyl-1-piperazinyl, or 3-or 3-tropanyl, each of which may optionally have another methyl substituent attached to the heterocyclic ring;R 1 is hydrogen or alkyl of 1 to 4 carbon atoms;R 2 is hydrogen, halogen or alkyl of 1 to 4 carbon atoms; andX is oxygen,--NH--or--N(CH. sub.3)--;and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as anti-ulcerogenics.
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- Analysis and stability of atropine sulfate and scopolamine hydrobromide. 1. Qualitative detection of alkaloids in the presence of their decomposition products. 73. Contribution to the problem of the use of plastic receptacles for liquid pharmaceuticals
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The authors deal with the qualitative determination of tropane alkaloid salts (atropine sulphate and scopolamine hydrobromide) in aqueous solutions in the presence of their decomposition products using thin-layer chromatography. Aqueous solutions of these tropane alkaloid salts were tested for stability after storage in glass and polyethylene containers under various conditions (pH value, temperature, ultra-violet irradiation, oxidative effects). Besides tropine, apoatropine, alpha- and beta-belladonine, further decomposition products showing a basic reaction (and in part not yet identified) were detected. The stability of solid atropine sulphate was studied by means of differential thermal analysis and mass spectrometry.
- Jira,Pohloudek-Fabini
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p. 645 - 649
(2007/10/02)
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- REDUCTIVE TRANSFORMATION OF A HYDROXYIODOKETONE OF 8-AZABICYCLOOCTANE INTO 7-AZABICYCLOHEPTANE WITH LITHIUM ALUMINIUM HYDRIDE
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1α,4β-Diodo-2α-acetoxytropan-3-one (2) and 1α-iodo-2α-acetoxytropan-3-one (3), which comprise 64percent of products emerging from the lead tetraacetate oxidation of tropan-3α-ol in presence of iodine, were subjected to lithium aluminium hydride reduction.The expected 2.3-dihydroxytropane was not obtained.Instead, a diol which was not prone to periodate oxidation, containing one primary and one secondary alkoholic groups was obtained.It was assigned the 1-hydroxymethyl-2α-hydroxy-7-methyl-7-azabicycloheptane structure (8), on the basis of spectroscopic evidences (ir, nmr and mass spectrometry) and some chemical transformations heptane (12)>.The reaction is understood as an initial β-elimination process, triggered by the delivery of hydride ion to the carbonyl function in the sequence 3 21 22, yielding a highly reactive enolate aldehyde (22) which is prone to an immediate internal aldol condensation (22) (23) (24), affording the observed diol (8) on further reduction of the a aldehydic group by LiALH4.The reductive deiodination of (3) into 2α-acetoxytropine (2b) or into 2α-hydroxytropan-3-one (25) was smoothly achieved by means of hydrogenation over Raney Nickel on mild basic conditions.
- Sarel, Shalom,Dykman, Edmund
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p. 719 - 734
(2007/10/02)
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