- Chiral separation of cathinone and amphetamine derivatives by HPLC/UV using sulfated β-cyclodextrin as chiral mobile phase additive
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In the last years the identification of new legal and illegal highs has become a huge challenge for the police and prosecution authorities. In an analytical context, only a few analytical methods are available to identify these new substances. Moreover, many of these recreational drugs are chiral and it is supposed that the enantiomers differ in their pharmacological potency. Since nonenantioselective synthesis is easier and cheaper, they are mainly sold as racemic mixtures. The goal of this research work was to develop an inexpensive method for the chiral separation of cathinones and amphetamines. This should help to discover if the substances are sold as racemic mixtures and give further information about their quality as well as their origin. Chiral separation of a set of 6 amphetamine and 25 cathinone derivatives, mainly purchased from various Internet shops, is presented. A LiChrospher 100 RP-18e, 250 x 4 mm, 5 μm served as the stationary phase. The chiral mobile phase consisted of methanol, water, and sulfated β-cyclodextrin. Measurements were performed under isocratic conditions in reversed phase mode using UV detection. Four model compounds of the two substance classes were used to optimize the mobile phase. Under final conditions (methanol:water 2.5:97.5 + 2% sulfated β-cyclodextrin) enantiomers of amphetamine and five derivatives were baseline separated within 23 min. In all, 17 cathinones were completely or partially chirally separated. However, as only 3 of 25 cathinones were baseline resolved, the application of this method is limited for cathinone analogs. Additionally, the results were compared with an RP-8e column. Copyright
- Taschwer, Magdalena,Seidl, Yvonne,Mohr, Stefan,Schmid, Martin G.
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p. 411 - 418
(2014/08/05)
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- Molecular basis of the selective binding of MDMA enantiomers to the alpha4beta2 nicotinic receptor subtype: Synthesis, pharmacological evaluation and mechanistic studies
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The α4β2 nicotinic acetylcholine receptor (nAChR) is a molecular target of 3,4-methylenedioxymethamphetamine (MDMA), a synthetic drug also known as ecstasy, and it modulates the MDMA-mediated reinforcing properties. However, the enantioselective preference of the α4β2 nAChR subtype still remains unknown. Since the two enantiomers exhibit different pharmacological profiles and stereoselective metabolism, the aim of this study is to assess a possible difference in the interaction of the MDMA enantiomers with this nAChR subtype. To this end, we report a novel simple, yet highly efficient enantioselective synthesis of the MDMA enantiomers, in which the key step is the diastereoselective reduction of imides derived from optically pure tert-butylsulfinamide. The enantioselective binding to the receptor is examined using [3H]epibatidine in a radioligand assay. Even though the two enantiomers induced a concentration-dependent binding displacement, (S)-MDMA has an inhibition constant 13-fold higher than (R)-MDMA, which shows a Hill's coefficient not significantly different from unity, implying a competitive interaction. Furthermore, when NGF-differentiated PC12 cells were pretreated with the compounds, a significant increase in binding of [3H] epibatidine was found for (R)-MDMA, indicating up-regulation of heteromeric nAChR in the cell surface. Finally, docking and molecular dynamics studies have been used to identify the binding mode of the two enantiomers, which provides a structural basis to justify the differences in affinity from the differential interactions played by the substituents at the stereogenic centre of MDMA. The results provide a basis to explore the distinct psychostimulant profiles of the MDMA enantiomers mediated by the α4β2 nAChR subtype.
- Llabrés, Salomé,García-Ratés, Sara,Cristóbal-Lecina, Edgar,Riera, Antoni,Borrell, José Ignacio,Camarasa, Jorge,Pubill, David,Luque, F. Javier,Escubedo, Elena
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- Synthesis and capillary electrophoretic analysis of enantiomerically enriched reference standards of MDMA and its main metabolites
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Enantiomerically-enriched (S)-3,4-methylenedioxymethamphetamine (MDMA) and its main metabolites (S)-4-hydroxy-3-methoxymethamphetamine (HMMA) and (S)-3,4-dihydroxymethamphetamine (HHMA) were prepared or unequivocal identification of the differential enantioselective metabolism of these compounds as well as for its application in the analysis of biological samples. Capillary electrophoresis with cyclodextrin derivatives and a chemical correlation of (S)-MDMA, (S)-HMMA and (S)-HHMA has been performed to assign the absolute stereochemistry of major isomers in analytical standards enriched with such enantiomers. Copyright
- Pizarro, Nieves,De la Torre, Rafael,Farre, Magi,Segura, Jordi,Llebaria, Amadeu,Joglar, Jesus
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p. 1085 - 1092
(2007/10/03)
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- Stereoselective synthesis of (s)-3,4-methylenedioxyamphetamines from (r)-cyanohydrins
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A stereoselective synthesis of (S)-3,4-methylenedioxyamphetamines (S)-7, which are highly interesting as psychoactive compounds, is described. Starting from readily available (R)-cyanohydrins (R)-2 the 2-amino-1-aryl alcohols (1R,2S)-4 were obtained with
- Effenberger, Franz,Jaeger, Juergen
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p. 1370 - 1374
(2007/10/03)
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- Derivatives of 1-(1,3-benzodioxol-5-yl)-2-butanamine: Representatives of a novel therapeutic class
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The α-ethyl phenethylamine derivative 1-(1,3-benzodioxol-5-yl)-2-butanamine was prepared. An asymmetric synthesis was used to prepare the enantiomers of this compound and the related α-methyl homologue (MDA). The racemates and enantiomers of both compounds were evaluated in the two-lever drug discrimination assay in rats trained to discriminate saline from 0.08 mg/kg of LSD tartrate. Stimulus generalization occurred with the racemate and the R-(-)enantiomer of the α-methyl homologue and the S-(+)enantiomer of the α-ethyl primary amine. No generalization occurred with the other enantiomers or with the N-methyl derivatives of either series. Human psychopharmacology studies revealed that the N-methyl derivative of the title compound was nonhallucinogenic and that it had a new, novel psychoactive effect. It is suggested that this compound is the prototype of a new pharmacologic class that may have value in facilitating psychotherapy and that this class be designated as entactogens.
- Nichols,Hoffman,Oberlender,Jacob III,Shulgin
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p. 2009 - 2015
(2007/10/02)
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