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The importance and structural diversity of chiral amines is well-demonstrated by the myriad nonenzymatic methods for their chemical production. In nature, the production of amines is performed by transamination rather than by reduction of an imine precursor derived from the corresponding ketone. Imine reductases, however, show great potential in the reduction of cyclic imines that are stable towards hydrolysis in aqueous reaction media. Here, we report the catalytic activity of two S-selective imine reductases towards 3,4-dihydroisoquinolines and 3,4-dihydro-β-carbolines and their activity in the direct reductive amination of ketone substrates. The crystal structures of the enzyme from Streptomyces sp. GF3546 in complex with the cofactor NADPH and from Streptomyces aurantiacus in native form have been solved and refined to a resolution of 1.9 A.

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A modified macrocyclic glycopeptide-based chiral stationary phase (CSP), prepared via Edman degradation of vancomycin, was evaluated as a chiral selector for the first time. Its applicability was compared with other macrocyclic glycopeptide-based CSPs: TeicoShell and VancoShell. In addition, another modified macrocyclic glycopeptide-based CSP, NicoShell, was further examined. Initial evaluation was focused on the complementary behavior with these glycopeptides. A screening procedure was used based on previous work for the enantiomeric separation of 50 chiral compounds including amino acids, pesticides, stimulants, and a variety of pharmaceuticals. Fast and efficient chiral separations resulted by using superficially porous (core-shell) particle supports. Overall, the vancomycin Edman degradation product (EDP) resembled TeicoShell with high enantioselectivity for acidic compounds in the polar ionic mode. The simultaneous enantiomeric separation of 5 racemic profens using liquid chromatography-mass spectrometry with EDP was performed in approximately 3?minutes. Other highlights include simultaneous liquid chromatography separations of rac-amphetamine and rac-methamphetamine with VancoShell, rac-pseudoephedrine and rac-ephedrine with NicoShell, and rac-dichlorprop and rac-haloxyfop with TeicoShell.

The invention also relates to pharmaceutical compositions comprising highly pure amphetamine and amphetamine-class compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds, and to methods of manufacturing, delivering, and using the amphetamine compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds.

We report the use of a chiral Cu(II) 3D metal-organic framework (MOF) based on the tripeptide Gly-l-His-Gly (GHG) for the enantioselective separation of metamphetamine and ephedrine. Monte Carlo simulations suggest that chiral recognition is linked to preferential binding of one of the enantiomers as a result of either stronger or additional H-bonds with the framework that lead to energetically more stable diastereomeric adducts. Solid-phase extraction of a racemic mixture by using Cu(GHG) as the extractive phase permits isolating >50% of the (+)-ephedrine enantiomer as target compound in only 4 min. To our knowledge, this represents the first example of a MOF capable of separating chiral polar drugs.

The invention also relates to pharmaceutical compositions comprising highly pure amphetamine and amphetamine-class compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds, and to methods of manufacturing, delivering, and using the amphetamine compounds resulting from the synthesis of chiral and racemic amphetamine derivatives by stereospecific, regioselective cuprate addition reaction with aziridine phosphoramidate compounds.

The invention relates generally to ephedrine or pseudoephedrine compositions containing biocompatible organoleptic (food flavoring) excipients that would prevent the illicit manufacture of methamphetamine from ephedrine or pseudoephedrine.

The invention relates generally to ephedrine or pseudoephedrine compositions containing biocompatible organoleptic excipients that would prevent the illicit manufacture of methamphetamine from ephedrine or pseudoephedrine. The organoleptic agents, typically used as food flavorings, are pyrazine based excipients, that when co-formulated with ephedrine or pseudoephedrine, prevent the isolation and converasion of pure methamphetamine.

The invention includes processes for the synthesis of amphetamine, dexamphetamine, methamphetamine, derivatives of these, including their salts, and novel precursors and intermediates obtained thereby, by synthesizing aziridine phosphoramidate compounds in specified solvents at specified temperatures, and then converting to a novel aryl or aryl-alkyl phosphoramidate precursors using an organometallic compound such as a copper salt, where the novel aryl or aryl-alkyl phosphoramidate precursor is then easily converted to the target compounds using known reactions,

We report the synthesis and reactivity of a chiral aminoborane displaying both rapid and reversible H2 activation. The catalyst shows exceptional reactivity in asymmetric hydrogenation of enamines and unhindered imines with stereoselectivities of up to 99% ee. DFT analysis of the reaction mechanism pointed to the importance of both repulsive steric and stabilizing intermolecular non-covalent forces in the stereodetermining hydride transfer step of the catalytic cycle.

A concise and high yielding enantioselective synthesis of (R)-selegiline, an anti-Parkinson's drug, (S)-benzphetamine, an anti-obesity agent, and (S)-sitagliptin, an anti-diabetic drug has been described starting from commercially available starting materials employing Evans' electrophilic azidation of chiral imide enolates as a key chiral inducing step, which proceeds in a highly diastereoselective manner (>99%).

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

The present invention relates to a method for the enzymatic hydroamination of C—C double bonds catalyzed by enzymes structurally and/or functionally related to phenylalanine ammonia lyase (PAL) isolated from microorganisms of Petroselinum crispum, Rhodoturula glutinis and/or functional active derivatives thereof.

Conjugation of the phenol derived from rivastigmine with amphetamines gave access to novel carbamate cholinesterase inhibitors. All compounds possessed increased affinity and selectivity for AChE compared to rivastigmine and were orally bioavailable. Comp

High specific activity (+)-amphetamine and (+)-methamphetamine were prepared by reductive dechlorination of (S)-(3′,5′-dichlorophenyl)- 2-propylazide and (S)-2′6′-dichloromethamphetamine, respectively. While the latter was readily obtained by resolution o

Samples of methamphetamine, prepared according to the most common synthetic pathways, were submitted to natural-abundance 2H NMR spectroscopy. The deuterium content at the various sites of the molecule was found to depend on its synthetic history. The technique provides a chemical fingerprint of methamphetamine samples and can give hints to trace back the starting materials and the synthetic procedures.

A process for synthesis of R-(-)-N, α -Dimethylphenethylamine (Levmetamfetamine, formula I), or S-(+)-N, α - Dimethyl phenethylamine (Methamphetamine, formula II ), from d-ephedrine of formula III or l-ephedrine formula IV, the process comprising the steps of (a) acylating the d- or l-ephedrine base of formula III or formula IV with an acylating agent to make a reaction mixture containing a N- acylated ephedrines of formula V or formula VI ; (b) deoxygenation of N-acylated ephedrines to make the compound of the formula VII or Formula VIII by using Raney Nickel catalyst ; and (c) acid hydrolysis of the above deoxygenated products to get the levmetamfetamine or methamphetamine.

Systems and methods providing for the introduction of a dye, particularly a xanthene dye, and more particularly a rhodamine dye, to liquid anhydrous ammonia to discourage theft of the anhydrous ammonia and provide for leak detection in storage vessels. The dye will stain objects which come into contact with the liquid anhydrous ammonia allowing for the detection of such contact. Generally, the staining will be visible to the naked eye, but may also fluoresce when exposed to a particular light source such as ultra violet (UV) light.

The resolution of N-methylamphetamine (MA) was carried out with the resolution agents O,O′-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA) and O,O′-di-p-toluoyl-(2R,3R)-tartaric acid (DPTTA). After partial diastereomeric salt formation, the unreacted enantiomers were extracted by supercritical fluid extraction (SFE). The effects of resolution agent molar ratio to the racemic mixture (mr), extraction pressure (P) and temperature (T) on the resolution efficiency were studied. The best chiral separation was obtained at a quarter of an equivalent resolution agent molar ratio for both resolution agents. Extraction conditions [pressure (100-200bar), temperature (33-63°C)] did not influence the resolution efficiency, which makes the enantiomer separation robust. In one extraction step, both enantiomers can be produced with high enantiomeric excess (ee) and remarkable yield (Y). Using DBTA as a resolution agent eeE=83%, YE=45% for the extract and eeR=82%, YR=42% for the raffinate were obtained.

Method for modulating responsiveness to corticosteroids in a subject are provided. In the method of the invention, an agent which antagonizes a factor that regulates production of IFN-γ in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an interferon-γ inducing factor (IGIF) antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders. Pharmaceutical compositions comprising an agent which antagonizes a factor that regulates production of IFN-γ in a subject, a corticosteroid and a pharmaceutically acceptable carrier are also provided. A preferred composition comprises an ICE inhibitor, a corticosteroid and a pharmaceutically acceptable carrier.

A number of tertiary N-allyl- and N-propargyl-substituted amines have been prepared by alkylation of secondary amines under solid-liquid phase-transfer catalysis conditions.

On reacting racemic amine bases with half equivalent amount of sodium-hydrogen-tartrate in a water-benzene solvent system, the mixed-neutral tartrate accumulates in the aqueous phase, while the free base concentrates in the organic phase, resulting in enantiomer separation without crystallization.

The reductive opening of aziridines 1a-c with lithium in the presence of a catalytic amount of naphthalene at -78 deg C led to the corresponding dianionic intermediates 2a-c, which are stable species under these reaction conditions and react with electrophilic reagents , (EtO)2CO, CH2=CHCO2Me, , PhCH=NPh, MeI, and CH2=CHCH2Br> to give, after hydrolysis with water, the corresponding difunctionalized compounds 3-5.When the reductive opening and the reaction with electrophiles were carried out on chiral aziridines 8 and 9, enantiomerically pure difunctionalized compounds 12 were obtained with the same stereochemistry, independently of the stereochemistry of diastereomeric starting aziridines 8 and 9.

(S)-N-methyl-α-methyl-phenethylamines 5a-d were obtained in 56-62 percent e.e. from chiral synthon (-)-N-cyanomethyl-4-phenyl-1,3-oxazolidine-1.

Determination of the stereochemical makeup of forensic samples can provide information about the source of the sample and a basis for intersample comparisons.The clandestine synthesis of methamphetamine and related amines continues to be a major source of these drugs of abuse.Most synthetic methods employ carbon-nitrogen bond formation and produce a racemic mixture; however, the individual enantiomers of ephedrine and pseudoephedrine contain the structural components of methamphetamine in chiral form.This paper will focus on the stereochemical course of the synthesis of methamphetamine via hydrogenolysis of the benzylic hydroxyl group in ephedrine and pseudoephedrine.The configurations of these amines were determined by liquid chromatography on an achiral C18 stationary phase following precolumn derivatization with 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate.

α-N-Acylamino acids have been developed as useful reagents for the preparation of optically pure α-aminoalkylaryl ketones.Protection of the amino group as either the ethoxycarbonyl or benzenesulfonyl derivative allows alanine to serve as an effective educt for the chirally specific synthesis of a variety of structures containing the phenylethylamine backbone.Benzene undergoes Friedel-Crafts acylation with the N-acylalanine acid chloride.Catalyst complexation with oxagenated aromatics, however, prohibits acylation of aryl ethers.An arylmetallo reaction scheme overcomes this problem and also affords regiospecificity not attainable in conventional acylations.As examples, optically pure ephedrines and amphetamines were directly synthesized without recourse to resolution since the chirality of the amino acid educt was entirely conserved throughout the process.

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