Determination of amino acids in human blood serum by reversed-phase high-performance liquid chromatography in the isocratic elution mode

A procedure is developed for the determination of 15 amino acids in human blood serum usingortho-phthalic aldehyde in combination with 2-mercaptoethanol or sodium sulfite as the reagent for the precolumn synthesis of derivatives with their subsequent separation by reversed-phase high-performance liquid chromatography in the isocratic elution mode using electrochemical detection. Conditions of the quantitative conversion of amino acids to corresponding derivatives were determined;ortho-phthalic—mercaptoethanol andortho-phthalic/sulfite derivatives of amino acids are stable during the whole cycle of analysis. The total time of separation is 80 min. The detection limits are 0.5-5 pmol (at the signal-to-noise ratio equal to 2). The procedure is used for the determination of glutamic acid, asparagine, serine, glutamine, histidine, taurine, alanine, arginine, methionine, isoleucine, ornithine, leucine, phenylalanine, lysine, and tryptophane in blood serum of healthy donors and of sick with alcoholism before and after treatment     

Bis-ortho-metalation/silylation of unprotected o-phthalic acids. Straightforward access to new silylated N-hydroxyphthalimide (NHPI) analogs

The one pot, in situ ortho-metalation/silylation of unprotected o-phthalic acids using lithium tetramethylpiperidide (LiTMP) and chlorotrimethylsilane is described. This method gives a straightforward access to silylated phthalic anhydrides. These can be easily converted into the corresponding silylated N-hydroxyphthalimide (NHPI) analogs, which are promising new aerobic oxidation catalysts.     

Spectrophotometric and Fluorimetric Determination of Amino Acids by Their Reaction with o-Phthalic Aldehyde in the Presence of Sulfite and Cyanide Ions

Optimum conditions were selected for the determination of amino acids by their reaction with o-phthalic aldehyde in the presence of sodium sulfite and potassium cyanide using glycine as an example. It was shown that the analytical characteristics of the proposed procedure are highly competitive with those of a widely employed procedure using 2-mercaptoethanol and that the stability of the analytical form (substituted isoindols) was much higher.     

Asymmetric synthesis of secondary benzylic alcohols via arene chromium tricarbonyl complexes

(Aryl aldehyde)- and (aryl ketone)-chromium tricarbonyl complexes ortho-substituted with the chiral auxiliary O-methyl-N-(α-methylbenzyl)hydroxylamine undergo diastereoselective addition of Grignard reagents and Super-Hydride^®, respectively, to give the corresponding secondary alcohols in high diastereoisomeric purity. These compounds may be easily decomplexed and deprotected to give the corresponding enantiopure amino alcohols.     

Synthèse de polyalcadiènes à extrémités fonctionnelles chlorure d'acide—étude de la réactivité de ces fonctions terminales

Two types of chemical modification of polymers are considered: attachment of functional groups as end-groups for diene polymers and also reaction of these end-groups with diamines. The deactivation, by means of the di-acid chloride of ortho-phthalic acid, of living polybutadiene or living polyisoprene leads to polydienes with molecules having one or two acid chloride end-groups. Chemical modification of these end-groups by an aliphatic diamine leads either to a new polymer having amine end-groups or to a polycondensation causing a substantial increase in molecular weight, depending upon the conditions.     

Kinetic study of bleaching of photoinduced forms of o-methylnitrobenzothiazoles

Photochromic properties of benzothiazole derivatives containing nitro and methyl groups in the ortho positions with respect to each other were studied by flash photolysis. The rate constant of bleaching of the corresponding photoinduced nitronic acids and their anions increases as the CH₃C-CNO₂ bond becomes longer. The application of the thermodynamic approach to predict the kinetic stability of nitronic acids is limited owing to specific intramolecular interactions. The lifetime of photoinduced nitronic acid anions tends to increase with rise in the chemical shift of the methyl protons.     

Determination of migrated phthalic acid residues into edible oils using a green mode of air-assisted liquid–liquid microextraction followed by high-performance liquid chromatography–diode array detector

In this study, for the first time, an organic solvent-free air-assisted liquid–liquid microextraction method has been reported for the extraction and preconcentration of phthalic acids (o-phthalic acid, m-phthalic acid, and p-phthalic acid) from edible oil samples. The method is based on the repeated aspirating/injection of an alkaline aqueous solution and the oil sample mixture in a conical bottom centrifuge tube to form a cloudy solution. After phase separation by centrifuging, the sedimented phase is directly analyzed by high-performance liquid chromatography–diode array detection. Under the optimum extraction conditions, the method showed low limits of detection and quantification between 0.11–0.29 and 0.28–0.91 ng mL^?1, respectively. Extraction recoveries and enrichment factors were from 81 to 97% and 406 to 489, respectively. The relative standard deviations for the analysis of 5 ng mL^?1 of each analyte were less than 5.9% for intraday (n = 6) and interday (n = 5) precisions. Finally, different oil samples were successfully analyzed using the proposed method and m-phthalic acid, and p-phthalic acid were determined in some of them at ng mL^?1 level.     

One‐Step Synthesis of Racemic α‐Amino Acids from Aldehydes,Amine Components,and Gaseous CO2 by the Aid of a Bismetal Reagent

α‐Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α‐amino acid can be divided into three basic components: an aldehyde, an amine, and carbon dioxide (CO₂). We report herein that a one‐step synthesis of α‐amino acids has been successfully achieved from these three basic and inexpensive chemicals with a single operation, in which the mixture of an aldehyde, a sulfonamide, and gaseous CO₂ was heated at 100 °C in the presence of Bu₃Sn‐SnBu₃ and CsF. In this one‐pot sequential protocol, two important intermediates (imine and α‐amino stannane) are involved and the stannyl anion generated in situ plays a crucial role, particularly for the efficient stannylation of the imine in the presence of proton sources and for promoting retrostannylation of the undesired α‐alkoxy stannane owing to its high stability and tolerance of the presence of proton sources. This methodology enabled the synthesis of a wide range of racemic arylglycine derivatives in high yields.     

Enantioselective synthesis of stimulus-responsive amino acid via asymmetric α-amination of aldehyde

Development of a methodology to control the function of peptides and proteins is an indispensable task in the field of chemical biology and drug delivery. Recently, we reported synthesis of racemic stimulus-responsive amino acids and their application for controlling peptidyl function. In this study, we report enantioselective synthesis of a key intermediate of stimulus-responsive amino acids via asymmetric α-amination reaction of an aldehyde. The obtained chiral intermediate was converted to an Fmoc protected UV-responsive amino acid with (S)-configuration, and it was successfully incorporated into a model peptide by Fmoc solid phase peptide synthesis.     

New Complexes of Nickel(II) Containing Macrocyclic Diaminodiiminepiperazine Ligands: Synthesis and Electrochemical Properties

Complexes of Ni(ClO₄)₂ with 1,4-bis(2-aminobenzyl)piperidine (1) and 1,4-bis(2-amino-4-tertbutyl)piperidine (2) and products of their cyclization with ortho-phthalic aldehyde in methanol [NiL3][ClO₄]₂ (3) and [NiL4][ClO₄]₂ (4), respectively, are synthesized. Complexes 1 and 2 can be reduced on a platinum electrode irreversibly. Cyclic complexes 3 and 4 undergo reduction reversibly or quasi-reversibly in two or three stages. The reduction products react with n-BuI or n–BuBr (Bu = butyl) via an inner-sphere mechanism of oxidative attachment, probably, with the formation of the Ni–C bond.     

The stereodivergent asymmetric synthesis of a range of 2-(1′-hydroxyalkyl)phenols

The use of the (S)-α-methylbenzyl group as a chiral auxiliary has allowed the diastereoselective ortho-deprotonation of a chromium tricarbonyl complexed phenoxy ring. When the resultant ortho-anion is treated with an aldehyde two diastereoisomeric complexes are formed, in relatively poor dr, which differ in the configuration of the newly formed benzylic stereogenic centre. However, both ortho-formylation followed by treatment with Grignard reagents and ortho-acylation followed by reduction with Super-Hydride^® were found to be completely diastereoselective, giving access to either epimer of the corresponding benzylic alcohol complexes in >99:1 dr. Subsequent oxidative removal of the chromium tricarbonyl unit, followed by cleavage of the O-α-methylbenzyl chiral auxiliary gives enantiopure 2-(1′-hydroxyalkyl)phenols. Following this stereodivergent procedure, either enantiomer of the product may be accessed from a single antipode of [(α-methylbenzyloxy)benzene]Cr(CO)₃.     

Asymmetric synthesis of deuterated and fluorinated aromatic α,α-disubstituted amino acid derivatives

We herein present organocatalytic approaches to synthesize fluorinated and deuterated α-substituted phenylglycine derivatives. Whereas the addition of diethyl azodicarboxylate to fluorinated α-substituted aldehydes furnishes chiral non-racemic compounds, the use of chloramine-T as a nitrogen source represents a rapid access to sulfamidated fluorinated amino acid precursors. Additionally, further functionalization was achieved through the palladium-catalyzed coupling of a p-bromosubstituted aldehyde with a range of fluorine or deuterium-containing boronic acids. Oxidation of the aldehyde function and cleavage of the protection group of the nitrogen give way to the free fluorinated unnatural amino acids.     

Uncatalyzed solventless Diels-Alder reaction of 2-amino-3-nitroacrylate: synthesis of new epimeric 2-amino-3-nitro-norbornene- and norbornane-2-carboxylic acids

A highly diastereoselective Diels-Alder reaction between cyclopentadiene and ethyl (Z)-2-N-Boc-amino-3-nitroacrylate in neat conditions affords the ethyl 2-t-butoxycarbonylamino-3-endo-nitro-bicyclo[2.2.1]hept-5-ene-2-exo-carboxylate: a new constrained carbocyclic amino acid. Catalytic hydrogenation of this cycloadduct gave the corresponding reduced norbornane derivative. A preliminary investigation into the chemistry of these two amino acids was performed. In particular, the epimerization to their corresponding 3-exo-nitro compounds by treatment both with acid and base was studied. From this study, valuable information on the endo/exo process at the C-3 carbon atom, as well as on the stability of the different stereomers, was obtained. The stability is closely related to the presence or the absence of the double bond in the ring and to the substitution pattern. Finally, deprotection of the amino acid function has been performed.     

A versatile synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones

A mild and general strategy for the synthesis of 2-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described. The seven-membered lactam is prepared by intramolecular amide bond formation from the intermediate amino acid, which is obtained either by reductive alkylation of a variety of amines with N-Boc,N-Me-ortho-formyl-Phe and Phth-ortho-formyl-Phe, or by reductive amination of a variety of aldehydes with N-Boc-ortho-aminomethyl-Phe.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

Thermodynamic analysis of the ionization of ortho and para toluic acids : influence of the medium on the hyperconjugative and steric effects

The hyperconjugative effect of the methyl group in the para and ortho position of the benzene ring is studied as a function of the medium. The ionization and solution enthalpies of ortho and para toluic acids have been measured in H₂O/DMSO mixtures. A study of the ortho effects by means of the linear combination of the ordinary polar, proximity polar and steric effects has also been performed.The methyl group both in ortho and para position seems to be forced out by the benzene ring at X_dmso= 0.5 mole fraction with a consequent decrease of hyperconjugation effect. A study of enthalpic and entropic contributions to substituent and reaction constants and the proton transfer process from ortho and para derivatives to benzoic acid, compared with the same process in the gaseous phase are also presented.     

Effects of ring substituents on enantioselective recognition of amino alcohols and acids in uryl-based binol receptors

The uryl-based binol aldehyde, (S)-2-hydroxy-2′-(3-phenyluryl-benzyl)-1,1′-binaphthyl-3-carboxaldehyde (1), binds 1,2-amino alcohols and amino acids stereoselectively by reversible formation of imine bond. Hydrogen bond (between uryl group and alcohol -OH moiety) plays an important role in the stereoselectivity of amino alcohols. Hence, any substituents on phenyl group in 1 are expected to affect H-bond ability of uryl group. To study the effects of ring substituents on the stereoselective recognition of amino alcohols, (substituted phenyl)uryl-based chiral binol receptors have been prepared. The receptors with electron-donating X substituents have been synthesized from (S)-2-methoxymethoxy-2′-hydroxy-1,1′-binaphthyl-3-carboxaldehyde and X-phenyluryl-benzyl bromide. The receptors with electron-withdrawing Y substituents, however, required a different synthetic strategy including transformation of an aldehyde to alcohol. The incorporation of the electron withdrawing groups slightly accelerated the stereoselective recognition property of the receptor. Though the acceleration is not so remarkable, this work demonstrates the versatile derivatization of 1 in achieving higher stereoselective recognition of 1,2-amino alcohols and stereoconversion of l-amino acids to d-amino acids.     

An efficient synthesis of sterically hindered arylboronic acids

Boronic acids are important intermediates and molecular recognition moieties in a wide variety of applications. In our research, we have found that the synthesis of ortho-substituted arylboronic acids is problematic with the commonly used bis(pinacolato)diboron in palladium-mediated borylation reactions. As a substitute, we have found that bis(neopentyl glycolato)diboron is a much more efficient borylation agent for the synthesis of sterically hindered ortho-substituted arylboronic acids.     

1,6‐Interactions between di­methyl­amino and aldehyde groups in two bi­phenyl derivatives

The title compounds, 2‐(di­methyl­amino)­bi­phenyl‐2′‐carbox­aldehyde, C₁₅H₁₅NO, and 2‐(di­methyl­amino)­bi­phenyl‐2′,6′‐dicarbox­aldehyde, C₁₆H₁₅­NO₂, show similar 1,6‐interactions [N?C=O 2.929 (3) to 3.029 (3) Å] between the di­methyl­amino and aldehyde groups located in the ortho positions of the two rings, which lie at 58.1 (1)–62.4 (1)° to each other.     

Synthesis of <Emphasis Type="Italic">ortho</Emphasis>-carboranyl derivatives of (<Emphasis Type="Italic">S</Emphasis>)-asparagine and (<Emphasis Type="Italic">S</Emphasis>)-glutamine

(S)-Asparagine and (S)-glutamine ortho-carboranyl derivatives with free amino and carboxy groups in the α-position were synthesized. By an example of N ^γ-(1,2-dicarba-closo-dodecarboran-3-yl)-(S)-glutamine it was demonstrated that the developed synthetic approach carboranyl derivatives of amino acids allowed the preparation of optically pure isomers.