Synthesis and crystal structure of 1-(aminomethyl)vinylphosphonic acid

A highly efficient and versatile approach to the synthesis of 1-(aminomethyl)vinylphosphonic acid, a constituent of the antibiotic A53868A, is reported. In the crystal, molecules of the acid are linked by strong, linear, symmetric hydrogen bonds involving hydrogen atoms of the phosphonic group.     

Cryomodification of drugs: Micronized amorphous state of carvedilol

By means of cryochemical modification, including substance evaporation in a stream of a heated gas-carrier with subsequent condensation of vapor on a surface, cooled up to the boiling temperature of liquid nitrogen (?196°C), the X-ray amorphous state of the drug carvedilol, (±)-1-(9H-carbazole-4-iloxy)-3-[2-(2-methoxyphenoxy)-ethylamino]propane-2-ol, was obtained. It is shown that, along with amorphization, cryomodification leads to micronization of the drug—the sizes of its particles decrease from an initial 5–10 up to 1–2 μm.     

Palladium-catalyzed synthesis of 2-(aminomethyl)indoles from ethyl 3-(o-trifluoroacetamidophenyl)-1-propargyl carbonate

[reaction: see text] The palladium-catalyzed reaction of ethyl 3-(o-trifluoroacetamidophenyl)-1-propargyl carbonate with piperazines in the presence of Pd(PPh(3))(4) in THF at 80 degrees C affords 2-(piperazin-1-ylmethyl)indoles in excellent yields. Good to excellent yields are also obtained with other secondary amines.     

Synthesis of chlorinated 2-(aminomethyl)- and 2-(alkoxymethyl)pyrroles

The synthesis of chlorinated 2-(hydroxymethyl)-, 2-(alkoxymethyl)- and 2-(aminomethyl)pyrroles via aromatization of 2-aryl-3,3-dichloro-5-(bromomethyl)pyrrolines and via reduction of 2-formyl- and 2-cyanopyrroles is described. The former methodology also provided new 2-[(alkyl- or phenylamino)methyl]pyrroles and a 2-(phosphonomethyl)pyrrole. Halogenated and methylene-spaced functionalized pyrroles are of particular interest for their pronounced physiological activities.     

Enantiospecific synthesis of the sugar amino acid (2S,5S)-5-(aminomethyl)-tetrahydrofuran-2-carboxylic acid

An enantiospecific synthesis of the tetrahydrofuran amino acid (2S,5S)-5-(aminomethyl)-tetrahydrofuran-2-carboxylic acid 1 is reported. The sugar enone 2-(S)-octyl 6-O-acetyl-3,4-dideoxy-α-d-glycero-hex-3-enopyranosid-2-ulose 2a, derived from galactose, was employed as a chiral precursor. The enone 2a was converted by chemical manipulation of the functional groups into the 6-azido-2-O-tosyl-3,4,6-trideoxy-d-erythro-hexono-1,5-lactone 9 as key intermediate. Methanolysis of 9 induced the opening of the lactone and the attack of the hydroxyl group at C-5 to C-2 with the displacement of the tosylate. This reaction led to the formation of the tetrahydrofuran ring of methyl (2S,5S)-5-(azidomethyl)-tetrahydrofuran-2-carboxylate 10, which was readily converted into 1. The overall yield of the sequence was 35%, and all the intermediates and the final product have been fully characterized. In addition, the preferential conformations in solution of lactone 9 and target molecule 1 have been established.     

An Efficient Synthesis of Optically Pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-ama) and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-aml)

An efficient synthesis of enantiomerically pure (R)- and (S)-2-(aminomethyl)alanine ((R)- and (S)-Ama) 1a and (R)- and (S)-2-(aminomethyl)leucine ((R)- and (S)-Aml) 1b is described (Schemes 1 and 2). Resolution of the racemic amino acids was achieved using L -phenylalanine cyclohexylamide ( 2 ) as chiral auxiliary. The free amino acids 1a, b were converted to the N^α-Boc,N^γ-Z-protected derivatives 11a, b (Scheme 3) ready for incorporation into peptides. Based on the three crystal structures of the diastereoisomeric peptides 8a, 8b , and 9b , the absolute configurations in both series were determined. β-Turn type-I geometries were observed for structures 8b and 9b , whereas 8a crystallized in an extended backbone conformation.     

Mechanistic investigation on 2-aza-spiro[4,5]decan-3-one formation from 1-(aminomethyl)cyclohexylacetic acid (gabapentin)

The intramolecular cyclization of the amino acid gabapentin has been studied in the pH range 2.24-11.15 at 80 °C in buffered solutions and constant ionic strength, and monitoring the progress of the process by fluorimetric method and proton NMR spectroscopy. From the profile of log k₀ versus pH two different acid-base equilibria are involved. The maximum rate is observed above pH 9.80 and the minimum rate has been measured between pH 5.15 and 6.21. The pK_a1 and pK_a2 have been determined by potentiometric titration to be 3.72 and 9.37, respectively. The buffer effect and the solvent kinetic isotopic effect suggest that the reaction is subject to general acid and general base catalysis. The process is sensitive to the gabapentin concentration (pH 10.45) and the pseudo-first order rate constant decrease with increasing the reagent concentration above 5.50×10⁻² M.     

A facile preparation of 2-(2-arylethyl)- and 2-(aminomethyl)indoles

An important process for the acid catalyzed cleavage of the benzoyl group from 3-benzoylindoles in high yield is identified and its application for the facile syntheses of 2-substituted indoles is demonstrated by preparing some 2-(2-arylethyl)- and 2-(aminomethyl)indoles from 1,3-dibenzoyl-2-bromomethylindole (7).     

Resolution and conformational analysis of diastereoisomeric esters of cis- and trans-2-(aminomethyl)-1-carboxycyclopropanes

(1R,2S)-, (1S,2R)-, (1R,2R)- and (1S,2S)-2-(Aminomethyl)-1-carboxycyclopropanes, conformationally restricted analogues of the neurotransmitter γ-aminobutyric acid (GABA), have been resolved by chromatographic separation of the corresponding diastereoisomeric esters which were formed between the cis- and trans-2-(acetamidomethyl)-1-carboxycyclopropanes with (R)-(−)-pantolactone. ¹H NMR, semi-empirical conformational analysis, ab initio (DFT) structure and NMR shielding tensor calculations of the cis-diastereoisomers allowed the absolute configuration assignments of the cis-amino acids.     

3,8,11,16-Tetrakis(aminomethyl)-1,2,9,10-tetrathia-cyclohexadecane tetra-trifluoroacetic acid: synthetic precursor to a novel thio-substituted diamine

Diamines have proven to be versatile intermediates in organic chemistry. Few diamines, however, can be appended to organic and inorganic supports without modification of the diamine functionality. We report the synthesis of 3,8,11,16-tetrakis-(N-BOC-aminomethyl)-1,2,9,10-tetrathia-cyclohexadecane (2) and 3,8,11,16-tetrakis(aminomethyl)-1,2,9,10-tetrathia-cyclohexadecane tetra-trifluoroacetic acid (3), potential precursors to 1,8-diamino-2,7-octanedithiol (4). Incorporation of the thiol units within the diamine backbone of 4 permits this compound to attach to organic and inorganic scaffolds. Spectral and chemical data showed that base hydrolysis of 1,8-bis(N-BOC-amino)-2,7-bis(acetylthio)octane (16) produced the 16-membered bis-disulfide 2 rather than the 8-membered ring dithiocane 17.     

Synthesis of 3-[(1-aryl)aminomethyl]indoles

We report the novel synthesis of various highly functionalized 3-arylaminomethyl indoles. This synthetic approach makes use of the directing ability of a bulky tert-butyldimethylsilyl-protecting group, which directs the condensation of an array of aromatic tosylaldimines specifically into the 3-position of the indole nucleus. The reactions, which occur under relatively mild conditions, afford the desired products in moderate yields. Prior to selective cleavage of the protecting group, the functionalized protected indoles also serve as attractive substrates for many future organic transformations.     

Synthesis of 1-arylmethyl-2-(2-cyanoethyl)aziridines and their rearrangement into novel 2-(aminomethyl)cyclopropanecarbonitriles

1-Arylmethyl-2-(bromomethyl)aziridines were transformed into novel 2-(2-cyanoethyl)aziridines upon treatment with alpha-lithiated trimethylsilylacetonitrile in THF in an efficient and straightforward approach. The latter aziridines underwent ring opening by reaction with benzyl bromide in acetonitrile, affording 5-amino-4-bromopentanenitriles through a regiospecific ring opening of intermediate aziridinium salts by bromide. Further elaboration of these gamma-bromonitriles resulted in the synthesis of novel 2-[N,N-bis(arylmethyl)aminomethyl]cyclopropanecarbonitriles in high yields by means of a 1,3-cyclization protocol upon treatment with KOtBu in THF.     

Synthesis and insecticidal activity of 4-(aminomethyl)-2H-1-benzothiopyran-2-ones (thiocoumarins) and related compounds

Bromination of 4-methyl-2H-1-benzothiopyran-2-ones (4-methylthiocoumarins) with bromine under irradiation of high-pressure mercury lamp gave 3-bromo-4-methylthiocoumarin, which reacted with secondary amine to give 4-(aminomethyl)thiocoumarins. The structure was determined by X-ray crystallographic analysis. A series of 4-methylthiocoumarin and related compounds were tested for insecticidal activity, and 4,6-dimethylthiocoumarin shows the most significant insecticidal activity against Nilaparvata lugens and Aphis gossypii. An introduction of an aminomethyl group in thiocoumarin results in improvement of activity against Tetranychus urticae and Spodoptera litura.     

Synthesis and crystalline and molecular structures of the morpholinylamide of N(R)-l-ephedrinylacetic acid

The synthesis of the morpholinylamide of N(R)-1-ephedrinylacetic acid has been achieved by the interaction of (5S,6R)-4,5-dimethyl-6-phenylmorpholin-2-one with morpholine, and its structure has been shown by IR and PMR spectroscopies and x-ray structural analysis.Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 108–112, January–February, 1999.     

α-(1H-Imidazol-1-yl)alkyl (IMIDA) carboxylic acid esters as prodrugs of carboxylic acid containing drugs

Synthesis of α-(1H-imidazol-1-yl)alkyl (IMIDA) carboxylic acid esters have been reported in 2-3 simple steps. α-(1H-Imidazol-1-yl)alkyl (IMIDA) carboxylic acid esters were found to be chemically labile and thus serve as novel prodrugs of carboxylic acids.     

Synthesis,structures and magnetic properties of cobalt(II) complexes derived from 5-(4-(1-(carboxymethyl)-1H-pyrazol-3-yl)phenyl)isophthalic acid ligand

Transition Metal Chemistry - Two complexes based on isophthalic acid ligand were successfully synthesized and structurally characterized. Compound 1 exhibits a three-dimensional...     

Zinc(Ⅱ) coordination architectures based on 5-(1H-tetrazol-1-yl)-isophthalic acid:Synthesis,structures and luminescent properties

With different pyridine-analogs as auxiliary ligands,three novel Zn(Ⅱ) complexes(1-3) based on 5-(1Htetrazol-1-yl) isophthalic acid(H_2L) have been synthesized and structurally characterized.Single crystal X-ray diffraction analyses of complexes 1-3 show the presence of tetrazolyl group,as well as the coordination behavior of the auxiliary ligands as critical factors determining the structures of such Zn(Ⅱ)-carboxyIate coordination architectures.In addition,the resulting complexes all exhibit luminescence properties in the solid state at room temperature.     

3-Cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines in the synthesis of substituted 3-(aminomethyl)pyridines

The reactions of substituted 3-cyanopyridine-2(1H)-thiones and 3-cyano-2-(methylthio)pyridines with lithium aluminum hydride in anhydrous diethyl ether afforded the corresponding 3-aminomethyl derivatives, which were used in the synthesis of the corresponding amides.     

Approaches to (R)- and (S)-1′-(1-aminoethyl)ferrocene-1-carboxylic acid derivatives

Lipase-catalyzed esterification of (±)-methyl 1′-(1-hydroxyethyl)ferrocene-1-carboxylate 4 afforded its (R)-acetate (−)-5 (ee = 99%) and (S)-(+)-4 (ee = 90%). Stereoretentive azidation/amination/acetylation of (R)-(−)-5 gave (R)-(+)-methyl 1′-(1-acetamidoethyl)ferrocene-1-carboxylate (R)-3 (ee = 98%). In a similar manner (S)-(+)-4 was converted into (S)-(−)-3 (ee = 84%). Both enantiomers of 3 were obtained in high chemical yields without a loss of enantiomeric purity. The title compounds can be coupled with natural amino acids and peptides on both C- and N-termini.