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A method for the synthesis of mixed-ligand gold glyconanoparticles with average particle size of 20–25 nm at widely variable ratio of the initial glycoligands on the basis of aldoses 6-mercaptohexanoyl hydrazones—condensation products of a series of natural aldoses (N-acetylamino-D-glucose, D-mannose, D-galactose, and L-fucose) with 6-mercaptohexanoic acid hydrazide—has been developed. It has been shown that the obtained gold glyconanoparticles exhibit low toxicity and are active against influenza A/Puerto Rico/8/34 (H1N1) virus at concentrations of 3 and 6 μg/mL.

The condensation products of natural monosaccharides L-fucose, L-rhamnose, N-acetylamino-D-glucose and N-acetylamino-D-mannose with thioglycolic acid hydrazide have a cyclic 1,3,4-thiadiazine structure or are presented in solution in DMSO-d6 by a tautomeric mixture of pyranose and 1,3,4-thiadiazine forms. It was shown that L-rhamnose and N-acetylamino-D-mannose mercaptoacetyl hydrazones exhibit high radioprotective activity, increasing the survival rate of mortally irradiated mice by 35–45%.

A method for the synthesis of gold glyconanoparticles with average particle size of 18–21 nm and low polydispersity index based on readily available thiolated compounds: 3-thiopropionylhydrazones of L-fucose, L-rhamnose, N-acetyl-D-glucosamine, and N-acetyl-D-mannosamine has been developed. It has been shown that some of the gold glyconanoparticles exhibit antitumor activity, and the initial thiolated glycoligands have shown strong radioprotective activity, increasing the survival rate of mortally irradiated mice by 50–70%.

In experiments in mice, the radioprotective efficacy of sugar-containing compounds was studied based on the condensation products of thioglycolic (TGH) and thiosalicylic (TSH) hydrazides with a series of natural aldoses: the monosaccharides D-glucose (Glс) and D-galactose (Gal) and the disaccharides D‑lactose (Lac) and D-maltose (Mal). It was shown that the use of Glc-TGH and Mal-TSH preparations increases the survival rate of deadly irradiated animals by 25% when administered 1 h before irradiation and by 40% when administered 24 h before irradiation. It is assumed that the leading role in the radioprotective activity of the drugs is played by the protection of the hematopoietic stem cells of the test animals.

The 1H and 13C NMR spectroscopy was used to study the structure of previously unknown aldose series condensation products (L-fucose, L-rhamnose, D-mannose, D-galactose, D-glucose, N-acetyl-D-glucosamine, N-acetyl-D-mannosamine, D-lactose and D-maltose) with 6-mercapto­hexanoic acid hydrazide—promising glycoligands of noble metal nanoparticles. It was shown that L-fucose, L-rhamnose, D-mannose, D-galactose and N-acetyl-D-mannosamine derivatives exist in solution in DMSO-d6 as a tautomeric mixture of open hydrazone and cyclic pyranose forms. The linear hydrazone form is represented by a set of Z′,E′-conformational isomers, which differ in the arrangement of substituents relative to the C–N amide bond in comparable amounts. The condensation products obtained on the basis of D-glucose, N-acetyl-D-glucosamine, D-lactose and D-maltose in the crystalline state and in solutions in DMSO-d6 have an exclusively cyclic pyranose structure represented by α,β-configurational isomers. A similar transition to the pyranose form is observed in solutions of all the studied compounds in D2O.

A procedure has been developed for the synthesis of gold glyconanoparticles with an average particle size of 15–30 nm and a low polydispersity index on the basis of natural hexose (d-glucose, d-galactose, d-mannose) sulfanylacetyl-, 3-sulfanylpropanoyl-, and 2-sulfanylbenzoylhydrazones and thiolated poly(2-deoxy-2-methacryloylamino-d-glucose).

A procedure has been developed for the synthesis of previously unknown aldose 4-[(ω-sulfanylalkyl) oxy]benzoylhydrazones (where alkyl is hexyl or decyl and aldoses are D-glucose, D-galactose, D-maltose, and D-lactose) that a repromising glycoligands for noble metal nanoparticles. According to the 1H and 13C NMR data, 4-[(ω-sulfanylalkyl)oxy]benzoylhydrazones derived from D-glucose, D-maltose, and D-lactose in crystal and in DMSO-d6 solution have exclusively the cyclic pyranose structure (α- and β-anomers). D-Galactose 4-[(ω-sulfanylalkyl)oxy]benzoylhydrazones in DMSO-d6 solution exist as tautomeric mixtures of cyclic pyranose and open-chain acylhydrazone structures.

A procedure has been developed for the synthesis of gold glyconanoparticles with an average particle size of 16–24 nm and low polydispersity index on the basis of accessible D-maltose and D-maltose 2-sulfanylacetyl-, 3-sulfanylpropanoyl-, and 2-sulfanylbenzoylhydrazones.

A method of synthesis of silver glyconanoparticles with average particle size 15–40 nm and low polydispersity index based on available 3-thiopropionylhydrazones of mono- and disaccharides has been elaborated. The prepared compounds have exhibited high antifungal, antibacterial, and antiviral activity and are promising for further comprehensive study.

The accessible D-ribose mercaptoacetyl-, 3-mercaptopropionyl-, and 2-mercaprobenzoylhydrazones were used to develop a method of synthesis of gold glyconanoparticles with the average particle diameter of 10–40 nm and a low polydispersity index.

A method of synthesis of 3-thiopropinyl derivatives of 5-oxo-1,3,4-benzothiadiazepine-4-acetic acid, potential antihypertensive drugs, vasopeptidase inhibitors, starting from 2-thiobenzoic acid hydrazide has been elaborated.

Basing on natural amino acid L-cysteine, commercially available aliphatic aldehydes, 2-acetylsulfanylbenzoyl chloride and 2,2′-disulfandiyldibenzoyl dichloride a synthesis was developed of (2R,4R)-2-alkyl-3-(2-mercaptobenzoyl)thiazolidine-4-carboxylic acids, potential antihypertensive compounds, inhibitors of angiotensin transforming enzyme.

It has been shown by 1H and 13C NMR spectroscopy that 2-mercaptobenzoyl-hydrazones of aliphatic and aromatic aldehydes exist in solution as tautomeric mixtures of linear and cyclic benzo-1,3,4-thiadiazepine forms. The linear hydrazone form is represented by (E,E')-and (E,Z')-conformational isomers, differing in the disposition relative to the amide C–N bond. Growing bulk of the alkyl substituent at the C=N bond of the aliphatic aldehydes derivatives decreases the fraction of the cyclic tautomer; therewith the logarithms of the constants of the chain-ring tautomeric equilibrium correlate with the ES steric constants of the alkyl substituents. In the series of the aromatic aldehydes 2-mercaptobenzoylhydrazones the linear tautomer prevails, and the logarithms of the tautomeric equilibrium constants KT correlate with the σ-constants of the substituents in the aromatic nucleus.

The structure of the condensation products of 2-hydroxybenzohydrazide, 2-aminobenzohydrazide, and N-methyl-N-(2-aminobenzo) hydrazide with a series of aldoses (L-arabinose, D-ribose, L- rhamnose, D-galactose, D-glucose, and D-mannose) was studied by 1H- an...

The structure of the condensation products of thiobenzohydrazide, 2-sulfanylacetohydrazide, 3-sulfanylpropiohydrazide, and 2-sulfanylbenzohydrazide with a series of aldoses (L-arabinose, D-ribose, L-rhamnose, D-galactose, D-glucose, and D-mannose) was studied by 1H- and 13C-NMR spectroscopy.

Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohexahy- dropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.

The natural amino acid L-cysteine, commercially available aldehydes, and 3-(acetylsulfanyl)propionyl chloride were used for the synthesis of 2-substituted (2R,4R)-3-(3-mercaptopropionyl)thiazolidine-4-carboxylic acids, potential antihypertensive drugs with angiotensin converting enzyme inhibiting action.

Proceeding from natural amino acid L-asparagine and commercially available aldehydes a stereoselective synthesis was developed of (2S,4S)-2-alkyl(aryl)-3-(3-sulfanylpropanoyl)-6-oxohydropyrimidine-4-carboxylic acids, potential antihypertensive drugs, inhibitors of the angiotensin converting enzyme.

The products of the condensation of aliphatic aldehydes with N-(2-aminobenzoyl)-N-methylhydrazine exist in DMSO-d6 solution as tautomeric mixtures of linear aldohydrazone and cyclic benzo-1,3,4-triazepine forms. The linear tautomer predominates for 2-aminobenzoyl-N-methylhydrazones of aromatic aldehydes. A tautomeric equilibrium is observed in DMSO-d6 for the products of the condensation of the hydrazide of 2-aminobenzoic acid with a series of aldoses. This equilibrium exists between α,β-isomeric pyranose forms and the open aldosohydrazone form. Isomeric conversion to the seven-membered benzo-1,3,4-triazepine form is observed for the products of the condensation of aldoses with N-(2-aminobenzoyl)-N-methylhydrazine.

It has been shown by 1H NMR spectroscopy that 2-mercaptobenzoylhydrazones of aromatic aldehydes 2-HSC6H4CONHN=CHC6H4X (X = 4-NO2, 3-NO2, 4-Br, H, 4-Me, 4-MeO, 4-Me2N) exist in DMSO-d6 solution as tautomeric mixtures of linear and cyclic benzo-1,3,4-thiadiazepine forms. The linear hydrazone form is represented by (E,Z′)-conformational isomers, differing in the disposition relative to the amide C–N bond. It was shown that the logarithm of the tautomeric equilibrium constant K T correlates with the σ-constants of the substituents in the aromatic nucleus.

The reaction of a series of 1,2-dicarbonyl compounds with thiocarbohydrazide and its 1- and 1,4-alkyl-(aryl)-substituted analogs has been studied. Treatment of diacetyl with the polynucleophiles indicated gives monohydrazones and/or 5-methylene-4,5-dihydro-2H-[1,2,4]triazine-3-thiones. Reaction of phenylglyoxal and benzil with thiocarbohydrazide yields 5-hydroxy- or 5-alkoxy-4,5-dihydro-2H-[1,2,4]triazine-3-thiones depending on the nature of the solvent. The products of condensation with 1,1-dimethylthiocarbohydrazide showed a thiocarbonohydrazone – 5-hydroxy-4,5-dihydro-2H-[1,2,4]tri-azine-3-thione ring-chain type equilibrium.

Condensation products of aliphatic aldehydes with 3-sulfanylpropionic acid hydrazide exist in solution as mixtures of linear hydrazone and cyclic 1,3,4-thiadiazepine tautomers. Hydrazones derived from 3-sulfanylpropionic acid hydrazide and aromatic aldehydes and ketones have mostly linear structures of different stereoisomers arising from Z-E isomerism with respect to the double C=N bond and restricted rotation about the C(O)-N bond. Condensation products of 3-sulfanylpropionohydrazide with a series of aldoses give rise to ring-chain-ring tautomeric equilibrium between α,β-isomeric pyranose structures, open-chain aldose hydrazone tautomer, and two diastereoisomeric seven-membered cyclic 1,3,4-thiadiazepine forms.

The isomeric transition of 2-aminobenzoylhydrazones of aliphatic aldehydes 2-H2NC6H4CONHN=CHAlk (Alk = Me, Et, Pr, Bu) in chloroform-d1 solution into the cyclic 1,2-dihydroquinazolin-4-one form has been studied. The structure of the obtained compounds was demonstrated by methods of 1H and 13C NMR spectroscopy.

Mercaptoacetylhydrazones of aliphatic and aromatic aldehydes exist in the solutions as tautomeric mixtures of open-chain and cyclic 1,3,4-thiadiazine forms. The linear hydrazone form consists of a set of isomers due to the configurational and conformational isomerism. At growing bulk of the alkyl substituent at the C=N bond of the aliphatic aldehydes derivatives decreases the fraction of the cyclic tautomer; therewith the logarithms of the constants of the chain-ring tautomeric equilibrium correlate with the steric constants of the alkyl substituents. In the series of the aromatic aldehydes mercaptoacetylhydrazones the linear tautomer prevails, and the equilibrium position is insignificantlyt affected at variation of the electronic characteristics of the substituents in the aromatic ring.

Condensation products of aroylacetic aldehydes with hydrazides of thioglycolic, 3-mercaptopropionic and 2-mercaptobenzoic acids exist in cyclic 1,3,4-thiadiazine, 1,3,4-thiadiazepine, or 1,3,4-benzothiadiazepine forms arising at the intramolecular addition of the mercapto group to the C=N bond of the initially formed hydrazone tautomer. The appearance of an alternative 5-hydroxy-2-pyrazoline form is favored by introduction of a strong electron-acceptor substituent into the aromatic ring of the 1,3-ketoaldehyde or by going over to benzoylacetone derivatives. In solutions the derivatives of aroylacetic aldehydes and of benzoylacetone show no tendency to tautomeric transition into linear hydrazine or enhydrazine forms.

1H and 13C NMR spectroscopy showed that the previously unknown thiosalicyloylhydrazones of aliphatic aldehydes, 2-HSC6H4CONHN=CHAlk (Alk = Me, Et, Pr, Bu, i-Pr, i-Bu) exist in solution as a tautomeric mixture of the linear and cyclic 1,3,4-benzothiadiazepine forms.

A stereoselective three-step synthesis of the title thiazolidine-4-carboxylic acids (III), potential lead compounds for the development of antihypertensive drugs with angiotensin converting enzyme inhibitory activity, starting from natural L-cysteine (I) is given.

The reaction of 2-aminomethylaniline with 1,3-dicarbonyl compounds gives a series of 1,2,3,4-tetrahydroquinazoline derivatives. A ring-chain tautomeric equilibrium of the type enamine-1,2,3,4-tetrahydroquinazoline is observed in solutions of these compounds and its position depends of the structure of the starting dicarbonyl component and the solvent polarity.

In this work 32 1,2,3,4-tetrahydroquinazoline derivatives were synthesized by the reaction of 2-aminomethylaniline with aldehydes and ketones and their ring-chain tautomerism studied by 1H, 13C and 15N NMR spectroscopy. The ketone, as well as the alkyl aldehyde, derivatives were found to favor exclusively ring forms, whereas tautomeric equilibria were observed for aryl aldehyde derivatives. For para-phenyl substituted compounds, good linear correlations were found between the Hammett–Brown σ+ parameter and log K (K=[ring]/[chain]) and also between σ+ and δNC (NC nitrogen chemical shift). An excellent correlation was also found between log K and δNC, which shows that the electronic character of the aryl substituent is carried by the conjugation effect to the environment of the nitrogen atom.

A universal scheme is proposed for the molecular design of heterocyclic recyclizations by replacing the exocyclic hydroxyl groups in exo-trig- ring-chain tautomeric molecules with substituted amines or hydrazines. The practical applicability of this approach is demonstrated by the condensations of 5-hydroxy-5-methyl-3-isoxazolidinones with thioaroyl-hydrazines and 2-aminomethylaniline. The condensation products were studied by modern 1H, 13C and 15N NMR spectroscopic methods using three solvents: CDC13, DMSO[D6] and CD3CN. The solvent was found to have a strong effect to the relative amounts of the tautomers.

It has been shown by 1H NMR spectroscopic methods that the previously unknown N-methyl-2-amino-benzoyl- and 2-mercaptobenzoylhydrazones of phenylacetic and 3-phenylpropionic aldehydes have cyclic benzo-1,2,4-triazepine and benzo-1,3,4-thiadiazepine structures respectively.

Condensation products of thioglycolic acid hydrazide with aldoses (L-arabinose, D-xylose, L-rhamnose, D-galactose, D-glucose, D-mannose) exist in the D2O solution as a tautomeric mixture of α,β-pyranose form and six-membered 1,3,4-thiadiazine form present as two diastereomers.

Salts of 1,1-dimethyl-2-acylhydrazines and 1,1-dialkylhydroxylamines add quantitatively to the double bond of oxo compounds with an unsubstituted vinyl substituent. The structure of the products depends on the nature of the substituent at the carbonyl group.1H and13C NMR spectroscopy indicated that acrolein derivatives have the cyclic structure of 1,1-dialkyl-2-acyl-3-hydroxypyrazolidinium and 2,2-dialkyl-5-hydroxyisoxazolidinium salts, while derivatives of phenyl vinyl ketone and hydrazide salts are the corresponding linear, hydrazinium salts. Ring-chain tautomerism was found for several derivatives of methyl vinyl ketone in solution.

Condensation products of title hydrazone with aliphatic and aromatic aldehydes as well as aldoses are synthesized.

The reaction of thiocarbohydrazides (I) with 1,2-dicarbonyl compounds of type (II) or (IV) leads to the formation of triazines.

Salts of N,N-dailkylhydroxylamines and β-dialkylhydrazides react with acrolein to give 2,2-dailkyl-5-hydroxyisoxazolidinium and 1,1-dialkyl-3-hydroxypyrazolidinium salts.

Salts of 1,1-dimethyl-2-acylhydrazines and 1,1-dialkylhydroxylamines add quantitatively to the double bond of oxo compounds with an unsubstituted vinyl substituent. The structure of the products depends on the nature of the substituent at the carbonyl group.1H and13C NMR spectroscopy indicated that acrolein derivatives have the cyclic structure of 1,1-dialkyl-2-acyl-3-hydroxypyrazolidinium and 2,2-dialkyl-5-hydroxyisoxazolidinium salts, while derivatives of phenyl vinyl ketone and hydrazide salts are the corresponding linear, hydrazinium salts. Ring-chain tautomerism was found for several derivatives of methyl vinyl ketone in solution.

Condensation products of thioglycolic acid hydrazide with aldoses (L-arabinose, D-xylose, L-rhamnose, D-galactose, D-glucose, D-mannose) exist in the D2O solution as a tautomeric mixture of α,β-pyranose form and six-membered 1,3,4-thiadiazine form present as two diastereomers.

Condensation products of aroylacetic aldehydes with hydrazides of thioglycolic, 3-mercaptopropionic and 2-mercaptobenzoic acids exist in cyclic 1,3,4-thiadiazine, 1,3,4-thiadiazepine, or 1,3,4-benzothiadiazepine forms arising at the intramolecular addition of the mercapto group to the C=N bond of the initially formed hydrazone tautomer. The appearance of an alternative 5-hydroxy-2-pyrazoline form is favored by introduction of a strong electron-acceptor substituent into the aromatic ring of the 1,3-ketoaldehyde or by going over to benzoylacetone derivatives. In solutions the derivatives of aroylacetic aldehydes and of benzoylacetone show no tendency to tautomeric transition into linear hydrazine or enhydrazine forms.

Goblyos et al. [1] have shown that ring–chain tautomerism is a characteristic feature of arylidene derivatives of 2-methylaminophenylamine with a substituent at the benzylic nitrogen atom. 1,2,3,4-Tetrahydroquinazoline structure has been assigned to the products of the reaction of aldehydes and ketones with 2-methylaminophenylamine [2, 3]. In previous work [4], we reported the tendency of imines of β-dicarbonyl compounds such as diketones, keto esters, and keto amides to exist as enamines. This suggested ring–chain tautomerism among the corresponding 2-methylaminophenylamine derivatives. In the present communication, we report the first example of such tautomerism A' . B for 3-(2-aminobenzylimino)-1-morpholin-4-yl-1-butanone (1), which is the product of the condensation of 2-methylaminophenylamine with acetoacetic acid morpholide. NMR spectral data indicate the instantaneous establishment of the A' . B equilibrium. The signal for sp-hybrid atom C(2) at 66.75 ppm serves as a characteristic feature for cyclic form B. Structure A should be eliminated due to the lack of a signal for the corresponding methylene group in the H NMR spectrum. All the signals of the linear form are in complete accord with structure A', which represents a cis isomer as indicated by NOE spectra. The nuclear Overhauser effect is observed for the signal of the C=C–H proton upon irradiation of the methyl protons, which indicates their cis orientation. Intramolecular hydrogen bonding between the NH proton and carbonyl group oxygen atom stabilizes the cis form. The nature of the solvent has a significant effect on the ratio of the tautomeric forms. The linear form predominates in DMSO-d6, while the ring form predominates in CDCl3. This phenomenon is well known for many tautomeric systems involving 1,3-dicarbonyl derivatives [4] (Scheme 1). We should note that the A' . B equilibrium differs fundamentally from the tautomerism of 1-substituted 2-methylaminophenylamines [1], in which the imine form participates at the anilinic nitrogen atom rather than the benzylic nitrogen atom. The NMR spectra were taken on a JEOL JNM-A-500 spectrometer. The H NMR spectra were taken at 500 MHz and the C NMR spectra were taken at 125 MHz, in DMSO-d6 at 30°C and in CDCl3 at 25°C. The 1D measurements involved NOE and determination of the major parameters of these spectra. The homonuclear H– H correlations involved the phase-sensitive DQF-COSY method, while the H–C heteronuclear correlations were determined by the HMQC method (for correlations through one bond, J1 = 145 MHz) and HMBC method (for correlations through two bonds, J2,3 = 8 Hz) with gradient selection. All the spectra were taken using standard pulse sequence sets.

Goblyos et al. [1] have shown that ring–chain tautomerism is a characteristic feature of arylidene derivatives of 2-methylaminophenylamine with a substituent at the benzylic nitrogen atom. 1,2,3,4-Tetrahydroquinazoline structure has been assigned to the products of the reaction of aldehydes and ketones with 2-methylaminophenylamine [2, 3]. In previous work [4], we reported the tendency of imines of β-dicarbonyl compounds such as diketones, keto esters, and keto amides to exist as enamines. This suggested ring–chain tautomerism among the corresponding 2-methylaminophenylamine derivatives. In the present communication, we report the first example of such tautomerism A' . B for 3-(2-aminobenzylimino)-1-morpholin-4-yl-1-butanone (1), which is the product of the condensation of 2-methylaminophenylamine with acetoacetic acid morpholide. NMR spectral data indicate the instantaneous establishment of the A' . B equilibrium. The signal for sp-hybrid atom C(2) at 66.75 ppm serves as a characteristic feature for cyclic form B. Structure A should be eliminated due to the lack of a signal for the corresponding methylene group in the H NMR spectrum. All the signals of the linear form are in complete accord with structure A', which represents a cis isomer as indicated by NOE spectra. The nuclear Overhauser effect is observed for the signal of the C=C–H proton upon irradiation of the methyl protons, which indicates their cis orientation. Intramolecular hydrogen bonding between the NH proton and carbonyl group oxygen atom stabilizes the cis form. The nature of the solvent has a significant effect on the ratio of the tautomeric forms. The linear form predominates in DMSO-d6, while the ring form predominates in CDCl3. This phenomenon is well known for many tautomeric systems involving 1,3-dicarbonyl derivatives [4] (Scheme 1). We should note that the A' . B equilibrium differs fundamentally from the tautomerism of 1-substituted 2-methylaminophenylamines [1], in which the imine form participates at the anilinic nitrogen atom rather than the benzylic nitrogen atom. The NMR spectra were taken on a JEOL JNM-A-500 spectrometer. The H NMR spectra were taken at 500 MHz and the C NMR spectra were taken at 125 MHz, in DMSO-d6 at 30°C and in CDCl3 at 25°C. The 1D measurements involved NOE and determination of the major parameters of these spectra. The homonuclear H– H correlations involved the phase-sensitive DQF-COSY method, while the H–C heteronuclear correlations were determined by the HMQC method (for correlations through one bond, J1 = 145 MHz) and HMBC method (for correlations through two bonds, J2,3 = 8 Hz) with gradient selection. All the spectra were taken using standard pulse sequence sets.

Salts of N,N-dailkylhydroxylamines and β-dialkylhydrazides react with acrolein to give 2,2-dailkyl-5-hydroxyisoxazolidinium and 1,1-dialkyl-3-hydroxypyrazolidinium salts.

Different species of lactobacilli, when grown together with salmonellae and shigellae, have been found to inhibit their growth and proliferation. The supernatants of the culture fluids of 8 species of lactobacilli have been shown to contain natural metabolites, other than lactic acid, with a wide spectrum of antibacterial activity with regard to different opportunistic aerobic and anaerobic microorganisms. The relationship between the antagonistic activity and the presence of plasmid DNA in a number of the most active antagonistic lactobacilli is discussed.