Mixed Anhydride Intermediates in the Reaction of 5(4H)‐Oxazolones with Phosphate Esters and Nucleotides

5(4H)‐Oxazolones can be formed through the activation of acylated α‐amino acids or of peptide C termini. They constitute potentially activated intermediates in the abiotic chemistry of peptides that preceded the origin of life or early stages of biology and are capable of yielding mixed carboxylic‐phosphoric anhydrides upon reaction with phosphate esters and nucleotides. Here, we present the results of a study aimed at investigating the chemistry that can be built through this interaction. As a matter of fact, the formation of mixed anhydrides with mononucleotides and nucleic acid models is shown to take place at positions involving a mono‐substituted phosphate group at the 3’‐ or 5’‐terminus but not at the internal phosphodiester linkages. In addition to the formation of mixed anhydrides, the subsequent intramolecular acyl or phosphoryl transfers taking place at the 3’‐terminus are considered to be particularly relevant to the common prebiotic chemistry of α‐amino acids and nucleotides.     

Recherches sur la formation et la transformation des esters LXXXIII [1]. Réactions de condensation et/ou de phosphorylation,en solution aqueuse,de divers composés organiques à fonctions ?OH,COOH, NH2, ou autres, à l'aide de polyphosphates linéaires ou cycliques

Amino acids and other derivatives are condensed in aqueous solutions in the presence of linear or cyclic polyphosphates (or other anhydrides of P acids). The best results are obtained in slightly alkaline media (pH 7.5 to 9.5). The reaction, which has been studied at 70°C and at room temperature, proceeds with relative ease even at room temperature. In the case of the cyclic polyphosphates, trimetaphosphate gave the best results as compared with tetra- and hexametaphosphate, and among the linear polyphosphates used the yields grew with the average length of the chain. The significance of this method of condensation as a general method and also in the context of chemical evolution is discussed. The author suggests that one of the pathways leading to the peptide bond formation involves the intermediate formation of aminoacyl phosphates or polyphosphates by the nucleophilic attack of the carboxylate group of the amino acid on the phosphorus of a linear or cyclic P? O? P bond, giving rise to the labile mixed anhydride, and subsequent nucleophilic attack of the amino nitrogen of a molecule of the amino acid, or of the aminoacyl phosphate already produced, on the C of the mixed anhydride with displacement of phosphate or polyphosphate and formation of a peptide bond. Other pathways may also involve the intermediate formation of phosphoramidates which may result from the reaction of amino groups (or ammonia) with trimetaphosphate in alkaline medium. Linear and cyclic polyphosphates (which are known to be phosphorylating agents of the OH (alcoholic) function in aqueous solutions at pH's above 7) phosphorylate serine, ethanolamine and threonine in aqueous solutions at pH 8–10 with yields up to 25%.     

Amyloid Aggregates Arise from Amino Acid Condensations under Prebiotic Conditions

Current theories on the origin of life reveal significant gaps in our understanding of the mechanisms that allowed simple chemical precursors to coalesce into the complex polymers that are needed to sustain life. The volcanic gas carbonyl sulfide (COS) is known to catalyze the condensation of amino acids under aqueous conditions, but the reported di‐, tri‐, and tetra‐peptides are too short to support a regular tertiary structure. Here, we demonstrate that alanine and valine, two of the proteinogenic amino acids believed to have been among the most abundant on a prebiotic earth, can polymerize into peptides and subsequently assemble into ordered amyloid fibers comprising a cross‐β‐sheet quaternary structure following COS‐activated continuous polymerization of as little as 1 mm amino acid. Furthermore, this spontaneous assembly is not limited to pure amino acids, since mixtures of glycine, alanine, aspartate, and valine yield similar structures.     

The synthesis of P-chiral amino acid-derived phosphonamidic anhydrides

The synthesis of an array of P-chiral amino acid-derived phosphonamidic anhydrides is described. These anhydrides are prepared by condensation of allylated amino acids 19-22 with methyl- or vinylphosphonic dichlorides 23 or 24 to produce three diastereomeric anhydrides 4-11a-c in good to excellent yields. The mechanistic issues concerning anhydride formation are discussed and supported by experimental results. Vinylphosphonamidic anhydrides 8-11 are further derivatized via the ring-closing metathesis (RCM) reaction to yield amino acid-derived bicyclic phosphonamidic anhydrides.     

Microwave-assisted reaction of peptide formation by amino acid with phosphate:Exploration of the most possible channels for the origin of life

The formation of peptides and then protein by small abiological molecules clusters such as amino acid is a key stage in the origin of life[1]. More and more ex- perimental results showed that phosphate plays an important role in the formation of biomolecules in prebiotic chemical evolution. The principal reservoirs of biochemical energy are phosphates (such as ATP). The peculiar role of phosphates in contemporary life might suggest its essential role in prebiotic energy conversion, syntheses …     

Derivatives for separation of amino acid enantiomers

Summary An optimum gas chromatographic separation of all protein amino acids in one run on capillaries coated with Chirasil-Val is difficult to achieve. Overlap of enantiomers of different amino acids may occur because the relative retention times depend upon the overall polarity of the stationary phase, the film thickness and the actual temperature programm. Employment of different derivatives formed by esterification with isopropanol, n-propanol, isobutanol and n-butanol and by acylation with trifluoroacetic, pentafluoropropionic and heptafluorobutyric anhydrides yields patterns of relative elution of all amino acid enantiomers. Thus, even critical pairs of amino acid enantiomers can be separated or shifted in their relative retention times. All amino acid enantiomers can be separated and quantitatively estimated.     

Modified Coumarins. 5. Amino-Acid Derivatives of 3-Hydroxy-7,8,9,10-tetrahydrobenzo[c]Chromen-6-one

Peptide-chemistry methods (symmetric anhydrides and activated esters) and the Mannich reaction were used to prepare various conjugates of amino acids with 7,8,9,10-tetrahydrobenzo[c]chromen-6-one in which the amino acids are bound to the coumarin by the C- or N-terminus.     

Partitioning behavior of amino acids in aqueous two-phase systems containing polyethylene glycol and phosphate buffer

The partitioning behavior of four amino acids, cysteine, phenylalanine, methionine, and lysine in 15 aqueous two-phase systems (ATPSs) with different polyethylene glycol (PEG) molecular weights and phosphate buffers has been studied in the present paper. The phase diagrams of the systems are investigated together with the effect of the PEG molecular weight and pH of the phosphate solutions. The composition of these systems and some parameters such as density and refractive index are determined. The influences of salts in ATPSs, side chain structure of the amino acids, pH of ATPSs, and the PEG molecular weight on the distribution ratios of the amino acids have been studied. This work is useful for the purification of amino acids and the separation of some proteins whose main surface exposed amino acid residues are these four amino acids, respectively.     

N-hydroxypeptides. I. Preparation of N-benzyloxy-α-amino acid anhydrides and their use in peptide synthesis

N-Benzyloxy-DL-α-amino acids are transformed with phosgen to N-benzyloxy-DL-α-amino acid anhydrides which react smoothly with the amino component of peptides to give the corresponding N-benzyloxypeptides.     

Infrared spectroscopy studies of the cyclic anhydride as the intermediate for the ester crosslinking of cotton cellulose by polycarboxylic acids. II. Comparison of different polycarboxylic acids

Polycarboxylic acids have been used as crosslinking agents for cotton cellulose. In our previous research, we used Fourier transform infrared (FT-IR) spectroscopy to investigate the formation of five-membered cyclic anhydride intermediates on cotton fabric by different polycarboxylic acids. In this research, we found that those polycarboxylic acids capable of forming both five- and six-membered cyclic anhydrides form only five-membered cyclic anhydrides. We compared the effectiveness of the polycarboxylic acids with different molecular structures for esterifying cellulose. Those polycarboxylic acids, which have their carboxyl groups bonded to the adjacent carbons of their molecular backbones and are capable of forming five-membered cyclic anhydrides, are more effective for esterifying cellulose than those polycarboxylic acids having their carboxyl groups bonded to the alternative carbons. The only six-membered cyclic anhydride identified is the anhydride formed on the cotton fabric treated with poly(acrylic acid). © 1996 John Wiley & Sons, Inc.     

Acylation of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine and tautomerism of the reaction products

The acylation of 2H,6H-2,6-dimethyl-4-amino-1,3,5-dithiazine with the chlorides and anhydrides of saturated carboxylic and sulfonic acids leads to N-monoacyl derivatives of dithiazine in 85–96% yields. It was established by IR and UV spectroscopy that 2H,6H-2,6-dimethyl-4-acylamino-1,3,5-dithiazines with donor substituents exist primarily in the amino form and that the equilibrium is shifted to favor the imino form for compounds with acceptor substituents to a greater degree in solutions than in the crystalline state.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 622–626, May, 1982.     

Préparation d'anhydrides à partir d'acides carboxyliques et de tétracyanoéthylène

Symmetrical anhydrides are easily obtained at 20–80°C, with good yields, by action of tetracyanoethylene on organic carboxylic acids in benzene solutions containing an heteroaromatic nitrogen base or another base.     

Laser-induced fluorescence detection in liquid chromatography after preliminary derivatization of carboxylic acid and primary amino groups

The development of selective derivatization for the determination of carboxylic acids, amino acids and peptides in aqueous solutions is described as a preliminary study for the determination of these compounds in biological materials. The derivatization reactions are completed before the liquid chromatographic separation and laser-induced fluorescence detection for which a continuous-wave argon-ion gas laser is used in the ultraviolet or visble mode. Carboxylic acid groups arre derivatized with 9-hydroxymethylathracene and primary amino groups are derivatized with fluorescein isothiocyanate. Detection limits, in aqueous solutions, for the carboxylic acid derivatives are ca. 190 fg (ultraviolet mode). In the visible mode, the detection limits are ca. 1 fg for the primary amino derivatives of amino acids and peptides. In al the chromatographic analyses, the derivatization mixtures are injected onto a standard reversed-phase or reversed- phase ion-pair system and conventional flow cells are used without expensive photon counting or optical systems.     

Activation of a carboxy group by dialkyl pyrocarbonates. Synthesis of symmetrical anhydrides and aryl esters of N-protected amino acids using di-tert-butyl pyrocarbonate as condensing reagent

It has been shown that di-tert-butyl pyrocarbonate can be used as a condensing reagent in the production of anhydrides and some aryl esters of carboxylic acids. The synthesis of anhydrides and of phenyl, p-nitrophenyl, -naphthyl, and quinolin-8-yl esters of N-protected amino acids is described.Institute of Biological and Medicinal Chemistry, Academy of Medical Sciences of the USSR, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 357–362, May–June, 1984.     

Efficient Procedure for the Preparation of Oligomer-Free N α -Fmoc Amino Acids

A two-step method is presented for the peptide-free, high-purity, and high-yield synthesis of N^α-Fmoc amino acids. The first step involves the preparation of stable dicyclohexylammonium–amino acid ionic adduct in acetone. Subsequently, the ionic adducts, on reaction with Fmoc-Nosu under mild alkaline conditions, give dipeptide-free N^α-Fmoc amino acids. The positive charge of the dicyclohexylammonium counterion in the ionic salt has a longer radius, moderating the nucleophilicity of the carboxylate ion of the amino acid and preventing by-products by arresting the formation of mixed anhydrides, the precursors of oligopeptide impurities.     

FT-IR and FT-raman spectroscopy study of the cyclic anhydride intermediates for esterification of cellulose: I. Formation of anhydrides without a catalyst

In recent years, extensive efforts have been made to find nonformaldehyde durable press finishes to replace the traditional formaldehyde-based reagents for producing wrinkle-free cotton fabrics. 1,2,3,4-butanetetracarboxylic acid (BTCA) has been the most effective nonformaldehyde crosslinking agent. Our previous research has indicated that a polycarboxylic acid esterifies cellulose in two steps: the formation of a 5-membered cyclic anhydride intermediate by the dehydration of two adjacent carboxyl groups, and the reaction between cellulose and the anhydride intermediate to form an ester linkage. In this research, we used Fourier transform infrared and Fourier transform Raman spectroscopy to study the formation of cyclic anhydride intermediates by BTCA and other polycarboxylic acids without the presence of a catalyst. We found that BTCA and other polycarboxylic acids in a crystalline state start to form 5-membered cyclic carboxylic anhydrides when the temperature reaches the vicinity of their melting points with the exception of bifunctional acids, which form cyclic anhydrides at temperatures much higher than their melting points. Intermolecular hydrogen bonding between carboxylic acid groups prevents the formation of the cyclic anhydride intermediates at lower temperatures. We also found that polycarboxylic acids in an amorphous state form cyclic anhydrides at much lower temperatures.     

The anilic acid number,an analytical index for testing dibasic acid anhydrides

For testing the purity of dibasic acid anhydrides and for analysing mixtures of these anhydrides with the corresponding free acids the determination of a new index number is recommended, indicated as the “anilic acid number”. The process is based on the fact that these acid anhydrides, when dissolved in acetone, under suitable experimental conditions can be added readily and quantitatively to aniline with resulting formation of the corresponding anilic acids.Immediately after addition, titration is effected with alcoholic potassium hydroxide on phenolphthalein. Pure dibasic acid anhydrides in this case yield the calculated anilic acid number. In the presence of free acids the values found are too high. The free acid content can be easily determined from the difference between the theoretical and the found anilic acid number.     

An SFG study of interfacial amino acids at the hydrophilic SiO2 and hydrophobic deuterated polystyrene surfaces

Sum frequency generation (SFG) vibrational spectroscopy was employed to characterize the interfacial structure of eight individual amino acids--L-phenylalanine, L-leucine, glycine, L-lysine, L-arginine, L-cysteine, L-alanine, and L-proline--in aqueous solution adsorbed at model hydrophilic and hydrophobic surfaces. Specifically, SFG vibrational spectra were obtained for the amino acids at the solid-liquid interface between both hydrophobic d(8)-polystyrene (d(8)-PS) and SiO(2) model surfaces and phosphate buffered saline (PBS) at pH 7.4. At the hydrophobic d(8)-PS surface, seven of the amino acids solutions investigated showed clear and identifiable C-H vibrational modes, with the exception being l-alanine. In the SFG spectra obtained at the hydrophilic SiO(2) surface, no C-H vibrational modes were observed from any of the amino acids studied. However, it was confirmed by quartz crystal microbalance that amino acids do adsorb to the SiO(2) interface, and the amino acid solutions were found to have a detectable and widely varying influence on the magnitude of SFG signal from water at the SiO(2)/PBS interface. This study provides the first known SFG spectra of several individual amino acids in aqueous solution at the solid-liquid interface and under physiological conditions.     

Quantitative Analysis of Mixtures of Various Linear Anhydrides and Carboxylic Acids

Only a few quantitative methods have been described to analyze mixtures of symmetric anhydrides, mixed anhydrides and their corresponding carboxylic acids. Reversed-phase liquid chromatography using acetonitrile-water as solvent was optimized for the quantitative determination of such mixtures obtained by reacting acetic or propionic anhydrides with various fatty acids (from C3 to C18). Complex mixtures containing up to three mixed anhydrides, four symmetric anhydrides and four carboxylic acids have been quantitatively analyzed successfully in a single run.     

Synthesis of Phosphonopeptides Using Pivaloyl Chloride

Abstract

Aminopnospnonic acids can be used as components in the synthesis of peptides resulting in the phosphonopeptides, which are interesting not only from the chemical point of view but also for their promising biological properties. An aminophosphonic acid unit can be attached to the C-terminus of amino acids or peptides by the usual methods of peptide chemistry. However, the specific properties of aminophos-phonates can sometimes lead to complications, for example formation of by products (1). de have tested the method of phospnonopeptide synthesis using pivaloyl chloride. It was found that dialkyl esters of 1-aminoalkylphosphonic acids readily react with mixed anhydrides of N-protected amino acid and pivalic acid to give the fully protected phosphonopeptides with good yields.