3,5-dinitro-1-(p-nitrophenyl)-4-pyridone as a novel protective group of primary amines

3,5-Dinitro-1-(p-nitrophenyl)-4-pyridone is proposed as a novel protective group for primary amines, especially amino acids, based on the results of the transformation of 1-substituted 3,5-dinitro-4-pyridones with primary amines.     

Synthesis of methyl esters of 5-amino-4-(substituted amino)-2-methylthio-7H-pyrrolo[2,3d]-pyrimidine-6-carboxylic acids

The optimum route for the synthesis of methyl esters of N-[(4-substituted amino)-5-cyano-2-methylthiopyrimidin-6-yl]amino acids (which are starting materials for preparing the methyl esters of the corresponding 5-amino-4-(substituted amino)pyrrolo[2,3-d]pyrimidine-6-carboxylic acids) is via subsequent reactions of 4,6-dichloro-2-methylthiopyrimidine-5-carbonitrile with amines and methyl glycinate. In some examples, the reaction of methyl N-(4-chloro-2-methylthio-6-pyrimidinyl)aminoacetate with amines occurs to give the corresponding acid amides. The previously unknown synthesized derivatives of pyrimidin-6-yl amino acids and 4,5-diaminopyrrolo[2,3-d]pyrimidine- 6-carboxylic acids possess fungicidal properties.Vilnius University, Vilnius 2006, Lithuania. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No 7, pp. 955–961, July, 2000.     

Calix[4]pyrrole-TCBQ assembly: a signal magnifier of TCBQ for colorimetric determining amino acids and amines

The interaction and colorimetric sensing properties of the calix[4]pyrrole-TCBQ charge-transfer complex with amino acids and amines in CHCl₃/EtOH/H₂O were investigated using UV/vis spectroscopic techniques. The obvious spectral and visual changes of the complex solution in the presence of basic amino acids (namely, lysine, arginine, and histidine) and aliphatic amines were observed, and the calix[4]pyrrole-TCBQ supramolecular assembly, like a ‘signal magnifier’, markedly improves sensing sensitivity and selectivity of TCBQ for amino acids and amines.     

4-(N,N-dimethylaminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole as chemilumigenic reagent for high performance liquid chromatographic peroxyoxalate chemiluminescence detection

4-(N,N-Dimethylaminosulphonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F), presented as a fluorogenic labelling reagent for amines and amino acids, is preferred for peroxyoxalate chemiluminescence (PO-CL) detection in high performance liquid chromatography. Amino acids and epinephrine derivatized with DBD-F were separated on a reversed phase column and detected at the femtomole level by the PO-CL detection system.     

AlMe(3)-promoted formation of amides from acids and amines

In the presence of AlMe(3), amines can be directly coupled with acids through dimethylaluminum amide intermediates to form the corresponding amides. A wide range of amines and acids including less nucleophilic amines, bulky amines, unprotected secondary amino acids, and acids with poor solubility were coupled smoothly to give the desired products in 55-98% yields.     

Sensitive derivatization reagents for hydroxyl and amino compounds for thin-layer or high-performance liquid chromatography with fluorescence detection

Three fluorescent derivatization reagents for compounds having hydroxyl and/or amino groups are described. 4-(2-Phthalimidyl)benzoyl chloride, 3-(2-phthalimidyl)benzoyl chloride and 3-(2-phthalimidyl)-4-methoxybenzoyl chloride, prepared from the corresponding phthalimidylbenzoic acid, were stable at room temperature and condensed quantitatively with alcohols, amines and amino acids in the presence of alkali under mild conditions to give strongly fluorescent derivatives. The derivatives were separated by thin-layer and high-performance liquid chromatography.     

Peptide and active ester formation by means of diaryl sulfites in pyridines

Peptides and active esters of amino acids were obtained under mild conditions by mixing sulfites with a mixture of carboxyl and amino or hydroxyl components in tertiary amines. Of several sulfites and tertiary amines examined, diphenyl sulphite and pyridine and 3- or 4-methylpyridines were most effective. The reaction mechanism is discussed.     

Characterisation of Tokaj wines based on free amino acids and biogenic amines using ion-exchange chromatography

Summary Tokaj wines (Szamorodni and Aszu wines) of Hungarian origin were investigated on the basis of free amino acids and biogenic amines. The separation and determination of these compounds was performed by an amino acid analyser equipped with an ion-exchange resin column. The total amount of free amino acids and biogenic amines was higher in Aszu wines than in Szamorodni wines. The main amino acids were proline and arginine, while the major biogenic amines were tyramine and putrescine. The free amino acid and biogenic amine content of Aszu wines depended on the vineyards the wines originated from. Presented at Balaton Symposium '01 on High-Performance Separation Methods, Siófok, Hungary, September 2–4, 2001     

Analytical potential of 6-oxy-(N-succinimidyl acetate)-9-(2'-methoxycarbonyl) fluorescein for the determination of amino compounds by capillary electrophoresis with laser-induced fluorescence detection

The analytical potential of a fluorescein analogue, 6-oxy-(N-succinimidyl acetate)-9-(2'-methoxycarbonyl) fluorescein (SAMF), for the first time synthesized in our laboratory, as a labeling reagent for the labeling and determination of amino compounds by capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection was investigated. Biogenic monoamines and amino acids were chosen as model analytes to evaluate the analytical possibilities of this approach. The derivatization conditions and separation parameters for the biogenic amines were optimized in detail. The derivatization was performed at 30 degrees C for 6 min in boric acid buffer (pH 8.0). The derivatives were baseline-separated in 15 min with 25 mM boric acid running buffer (pH 9.0), containing 24 mM SDS and 12.5% v/v acetonitrile. The concentration detection limit for biogenic amines reaches 8 x 10(-11) mol.L(-1) (signal-to-noise ratio = 3). The application of CE in the analysis of the SAMF-derivatized amino acids was also exploited. The optimal running buffer for amino acids suggested that weak acidic background electrolyte offered better separation than the basic one. The proposed method was applied to the determination of biogenic amines in three different beer samples with satisfying recoveries varying from 92.8% to 104.8%. Finally, comparison of several fluorescein-based probes for amino compounds was discussed. With good labeling reaction, excellent photostability, pH-independent fluorescence (pH 4-9), and the resultant widely suited running buffer pH, SAMF has a great prospect in the determination of amino compounds in CE.     

Advances in the o-phthalaldehyde derivatizations. Comeback to the o-phthalaldehyde-ethanethiol reagent

The main aims of this work were (a) to present the characteristics and stability of the o-phthalaldehyde (OPA)-ethanethiol (ET) derivatives of 22 amino acids, including the believed-to-be less stable OPA derivatives providing glycine, gamma-aminobutyric acid, beta-alanine, histidine, ornithine, lysine and the C(1)-C(5) aliphatic amines; (b) to compare the stability properties of the most common amino acids and amines as OPA-ET-fluorenylmethyl chloroformate (FMOC) derivatives to the corresponding ones obtained from OPA reagents containing various (SH)-additives; (c) to show the molar responses of alanine and lysine depending on the OPA reagent's composition; as well as (d) to prove the practical utility of these basic researches, by the simultaneous HPLC separation of 22 amino acids and 15 amines as their OPA-ET-FMOC derivatives. Investigations have been carried out by varying the composition of the reagents, the molar ratios of reactants and the reaction time, applying diode array and fluorescence detections simultaneously. Average reproducibility of quantitations, characterized with the relative standard deviations (RSDs) based on the fluorescence intensities of derivatives, in the order of listing, proved to be 1.2-5.9% for amino acids and 1.1-8.7% for amines. The practical utility of the method is demonstrated by the analysis of the amino acid and amine contents of mouse tissues, with an average reproducibility of 3.5%.     

Recent Applications of α-Metalated Isocyanides in Organic Synthesis

Being both nucleophilic and electrophilic, α-metalated isocyanides can add to polar double bonds, forming heterocycles. They are also synthons for α-metalated primary amines. This article describes recent or improved procedures for their use in organic synthesis: (1) In heterocyclic syntheses to give 2-oxazolines, 2-imidazolines, 2-thiazolines, oxazoles and oligooxazoles, thiazoles, triazoles, imidazolinones, pyrroles, 5,6-dihydro-1,3-oxazines and -thiazines, and (via cycloaddition with nitrones) 2-imidazolidinones. (2) In the field of formylaminomethylenation, for example transformation of estrone methyl ether and a keto sugar into the corresponding α-formylaminoacrylic esters, and the conversion of aldehydes and ketones by 3- and 4-pyridyl-methyl isocyanides into N-(1-pyridyl-1-alkenyl)formamides and their hydrolysis to 3- and 4-acylpyridines. (3) In connection with the use of α-metalated isocyanides as synthons for α-metalated primary amines, the author demonstrates how they may be used for preparation of 1,2- and 1,3-amino alcohols, 1,2-diamines, 2,3-diaminoalkanoic acids and for synthesis of higher amino acids starting from simple amino acids.     

A novel generation of coupling reagents. Enantiodifferentiating coupling reagents prepared in situ from 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) and chiral tertiary amines

Coupling of racemic N-protected amino acids with amino components by means of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) in the presence of chiral tertiary amines such as strychnine, brucine, and sparteine proceeds enantioselectively, affording appropriate amides or dipeptides in 69-85% yield. The configuration of the preferred enantiomer and enantiomeric enrichment depend on the structures of the amine and carboxylic acid. Calculated Kagan enantioselectivity parameters (s) are in the range 1.6-195. Chiral triazinylammonium chlorides formed in situ from CDMT and chiral tertiary amines are postulated as reactive intermediates involved in the process of enantioselective activation of N-protected amino acids.     

A synthesis of (S)-α-(fluorodiphenylmethyl)alkylamines by HF–pyridine treatment of 4-alkyl-5,5-diphenyl-oxazolidinones

Treatment of enantiomerically pure (S)-4-alkyl-5,5-diphenyl-oxazolidinones, themselves derived from appropriate amino acids, with HF–pyridine (Olah's reagent) generated a range of (S)-α-(fluorodiphenylmethyl)alkylamines. These compounds represent a novel range of fluorinated chiral amines.     

Isothiocyanato-calix[4]phyrin-(1,1,1,1): a useful intermediate for the synthesis of derivatised anion sensors

A calix[4]phyrin-(1,1,1,1) substituted with a 4-isothiocyanatophenyl group has been synthesised and used to attach the macrocycle to a solid support. The NCS group can also be used to further functionalise the calix[4]phyrin-(1,1,1,1) by reaction with amines and amino acids. Stability constants for anion binding by the calix[4]phyrin-(1,1,1,1) are reported and these show a clear ability to differentiate F(-) and HSO(4)(-) from Cl(-), Br(-), I(-) which can be detected by both NMR and UV-visible spectroscopy.     

A solid-phase synthetic route to unnatural amino acids with diverse side-chain substitutions

Reacting imine derivatives of resin-bound amino acids with alpha,omega-dihaloalkanes provides highly versatile intermediates to racemic alpha,alpha-disubstituted amino acids with a wide variety of side-chain functionality. Two strategies were developed to convert the intermediate omega-chloro or omega-bromo derivatives to the desired products. Together, they allow the creation of amino acids with diverse functionalities (omega-chlorides, nitriles, azides, acetates, thioacetates, thioethers, secondary and tertiary aliphatic amines, and anilines) placed at varying chain lengths (2-5) from the alpha-center of the amino acid.     

New aspects of the simultaneous analysis of amino acids and amines as their o-phthaldialdehyde derivatives by high-performance liquid chromatography. Analysis of wine,beer and vinegar

A new high-performance liquid chromatography method is described for the simultaneous quantitation of amino acids and amines for 37 compounds (20 amino acids + 17 amines), as their o-phthaldialdehyde (OPA)-3-mercaptopropionic acid derivatives, within 53 min. Based on previously documented stoichiometric and reaction mechanism studies, derivatizations have been carried out with the OPA-SH-group = 1:50 containing reagents. Reliability and reproducibility of analyses have been considerably improved. Average reproducibility data in a wide concentration range of derivatives had RSD < or = 3.4%.     

Determination of enantiomeric excess and concentration of unprotected amino acids, amines, amino alcohols, and carboxylic acids by competitive binding assays with a chiral scandium complex

A practical UV-vis sensing method for enantioselective microanalysis of unprotected amino acids, amines, amino alcohols, and carboxylic acids in aqueous solution has been developed. Both concentration and enantiomeric composition of a wide range of chiral substrates can be determined with high accuracy by two simple competitive binding assays using a scandium complex derived from 1,8-bis(3-(3',5'-dimethylphenyl)-9-acridyl)naphthalene N,N'-dioxide.     

Effect of the residual silanol group protection on the liquid chromatographic resolution of racemic primary amino compounds on a chiral stationary phase based on optically active (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6

A liquid chromatographic chiral stationary phase (CSP) based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6, which has been utilized in the resolution of alpha-amino acids, amines and amino alcohols, was treated with excess of n-octyltriethoxysilane to prepare a new improved CSP. The residual silanol groups of the original CSP were protected by n-octyl groups in the new CSP. The chiral recognition ability of the new CSP was superior to that of the original CSP in the resolution of alpha-amino acids, amines and amino alcohols. Retention factors (k1) for the resolution of alpha-amino acids were lower on the new CSP than on the original CSP while those for the resolution of amines and amino alcohols were higher on the new CSP than on the original CSP. The improved chiral recognition ability of the new CSP and the retention behaviors of the two enantiomers on the new CSP have been rationalized to stem from the removal of the non-enantioselective interactions between the analytes and the residual silanol groups of the original CSP and the improved lipophilicity of the CSP.     

Determination of absolute configurations of amines and amino acids using nonchiral derivatizing agents (NCDA) and deuterium NMR

Enantiomeric analysis and empirical determination of the absolute configuration of amines and amino acids can be easily performed using acetyl-d(3) chloride as a nonchiral derivatizing agent (deuterium probe) and deuterium NMR in a chiral solvent (Courtieu's method). In the case of amino acids, derivatization to amido esters, performed with methanol-d(4) and acetyl-d(3) chloride, gives a double opportunity for enantiomeric analysis.     

Benzotriazole-mediated syntheses of depsipeptides and oligoesters

Reactions of O-Pg(α-hydroxyacyl)benzotriazoles with (a) unprotected α-hydroxycarboxylic acids, (b) amino acids, and (c) amines afforded, respectively, chirally pure (a) oligoesters, (b) depsidipeptides, and (c) amide conjugates (yields 52-94%). N-Pg(α-Aminoacyl)benzotriazoles reacted with α-hydroxycarboxylic acids to yield depsidipeptides (47-87%). N-Pg(depsidipeptidoyl)benzotriazoles, obtained from depsidipeptides, gave depsitripeptides (yields 55-78%) on reaction with amino acids and α-hydroxycarboxylic acids. O-Acylation of α-hydroxycarboxylic acids with N-Pg(α-aminoacyl)benzotriazoles followed by deprotection produced unprotected depsides useful for the preparation of depsitripeptides.