E. V. Voronina

Synthesis and Antimicrobial Activity of 3-Hydroxy- and 3-Arylamino-5-aryl-4-acyl-1-(pyridyl)-3-pyrrolin-2-ones

Previously we reported on the synthesis of 3-hydroxy-3pyrrolin-2-ones containing aromatic substituents in position 5 and aroyl [1 – 4] or arylsulfonyl [2, 5] in position 4. It was found that these compounds possess, depending on the character of substituent in position 1 of the heterocycle, antimicrobial [6], antiviral [6, 7], analgesic [6], and antiamnesic [8] properties. For elucidating the influence of the character of substituents in position 1 on the biological activity of 3-pyrrolin-2ones, especially on their antimicrobial properties, it was of interest to introduce a pyridine residue into this position. In order to obtain 5-aryl-4-acyl-1-(2-pyridyl)-3-hydroxy-3-pyrrolin-2-ones (I – XV), we have studied the reactions of acylpyruvic acid esters with a mixture of aromatic aldehydes and 2-aminopyridine or 5-bromo-2-aminopyridine. R = H (XVI, XVII), CH3 (XVIII), Br (XIX), C2H5O (XX), CH3O (XXI); R 1 =C H 3 (I – V, XVI), C6H5 (VI – XI, XVII – XXI), 4-BrC6H4 (XII, XIII),

Synthesis and antimicrobial activity of 1-(4-hydroxyphenyl)-4-acyl-5-aryl-3-hydroxy-3-pyrrolin-2-ones

The reaction of methyl esters of acylpyruvic acids, 4-aminophenols, and aromatic aldehydes leads to the formation of 1-(4-hydroxyphenyl)-4-acyl-5-aryl-3-hydroxy-3-pyrrolin-2-ones. The proposed structures of the synthesized compounds were confirmed by IR and PMR spectroscopy. The antibacterial activity of some of the newly synthesized compounds was studied.

Synthesis and antimicrobial activity of 4-aroyl-3-hydroxy-2,5-dihydrofuran-2-ones and their derivatives

Previously we reported on substances possessing antiinflammatory [1], antiviral [2], nootropic [3], and antimicrobial [3, 4] properties in 1-substituted 5-aryl-4acyl-3-hydroxy-3-pyrrolin-2-ones. In continuation of the search for new compounds with antimicrobial activity in the series of 5-membered hydrogenated 2,3-dioxoheterocycles, we have synthesized a series of 4,5-substituted tetrahydrofurandiones in order to determine how the transition from pyrrolinediones to their closest analogs belonging to the furan series affects the antimicrobial properties. In the first stage, methyl ethers of aroylpyruvic acids were condensed with aromatic aldehydes and formalin in the presence of potassium carbonate. By acidifying these reaction mixtures according to Foldi et al. [5], we obtained 5-R-4-aroyl-3-hydroxy-2,5-dihydrofuran-2-ones (I X) with R = H or aryl. Compounds I X appear as colorless crystalline substances soluble in DMF, DMSO, glacial acetic acid, and chloroform. The IR spectra exhibit absorption bands related to double bonds (at 1600 1632 c m t), carbonyl groups of the acyl substituents (16401688 cmt ) , lactone carbonyls (1750 1760 e m l), and a broad band due to stretching vibrations of the hydroxy groups associated by intramolecular hydrogen bonds (3200 3288 cmt). The tH NMR spectra of the 5-aryl-substituted compounds display a singlet signal due to methine proton in position 5 of the heterocycle (at 6 . 5 7 6.80 ppm). A singlet signal due to protons of the methylene group at position 5 of the heterocycle in the spectrum of unsubstituted tetrahydrofuran-2,3-diones (R = H) is observed at 5.22 5.52 ppm and a multiplet related to the aromatic protons, at 7.64 8.00 ppm. The absence o f signals due to enol hydroxy groups is probably explained by considerable broadening of these signals caused by the intraand intermolecular hydrogen bonds. The

Synthesis and antimicrobial activity of n,7-diaryl-5-methyl-4,7-dihydrotetrazolo[1,5- a ] pyrimidine-6-arboxamides

N,7-Diaryl-5-methyl-4,7-dihydrotetrazolo[1,5-a]pyrimidine-6-carboxamides were synthesized by three-component reaction of acetoacetanilides (2-methylacetoacetanilide, 2,4-dimethylacetoacetanilide, 4-chloroacetoacetanilide, o-acetoacetanilide) with a mixture of aromatic aldehyde and 5-aminotetrazole. The proposed structures are confirmed by IR and PMR spectroscopy and mass spectrometry. The synthesized compounds are characterized with respect to antimicrobial activity.

Synthesis, properties, and biological activity of β-aroylpyruvoyl hydrazides oF N-methyl- and N-phenylanthranilic acid

Anthranilic acid hydrazides exhibit antistaphylococcus [ I ] and antiaggregation activity with respect to blood plasma thrombocytes [2]. They also can be used for the syntheses of nitrogen-containing heterocycles exhibiting various pharmacological effects [3]. Aroylpyruvic acid hydrazides exhibit a bacteriostatic effect against Staphylococcus aureus and Escherichia coli [4], inhibit the growth of A and B influenza viruses, and exhibit an antiinflammatory effect [5]. In searching for novel biologically active compounds we synthesized 13-aroylpyruvoyl hydrazides of N-methyland Nphenylanthranilic acids ( IVXVI) and studied their antiinflammatory and antimicrobial activity. The target products were obtained by the reaction of 5aryl-2,3-dihydrofuran-2,3-diones (I) with hydrazides of Nmethyland N-phenylanthranilic acids (I1 and III) in an inert solvent at room temperature. Compounds I1 and III qualify as binucleohilic reagents. The nucleophilic centers are the !3amino group ofhydrazide moiety and the aromatic N-methyland N-phenyl amino groups. The nucleophilic properties of the hydrazide 13-amino group are most pronounced, because nucleophilicity of the aromatic amino group is reduced due to the positive mesomeric effect. In addition, the steric effects can also affect the reactivity of this group [6]. It is well known that in the case of nonequivalent nucleophilic centers the furandione ring is opened under the action of the strongest nucleophilic agent [7]. The synthesized compounds are yellow solids, almost insoluble in water, and give like other ariylpyruvic acid derivatives a cherry color when reacted with an ethanol solution of FeCI3. This indicates that the compounds exist in the enol. The previous studies have established that cc-carbonyl of aroylpyruvic moiety undergoes enolization in any case [8].

SYNTHESIS AND ANTIMICROBIOGICAL ACTIVITY OF 4-ACYL-3-HYDROXYSPIRO-(2,5-DIHYDROFURAN-5,2- INDAN)-2,1,3-TRIONES

A series of 4-acyl-3-hydroxyspiro-[2,5-dihydrofuran-5,2′-indan]-2,l′,3′-triones (I–XV) have been synthesized via the interaction of methyl esters of acylpyruvic acids with ninhydrin for 3–4 h in water at a temperature of 50–60°C in the presence of dioxane. The target products were obtained with yields within 39–95%. All compounds have been characterized by IR and 1H NMR spectra, and some of the products were tested for their antimicrobial activity.

Synthesis and antimicrobial activity of 2,6-dimethyl-3,5-dialkoxycarbonyl-4-phenyl- 1,4-dihydropyridines

Reaction of acetoacetic esters, aromatic aldehydes, and ammonia formed under Hantzsch conditions 2,6-dimethyl-3,5-dialkoxycarbonyl-1,4-dihydropyridines. The structures of the products were established using mass, IR, and PMR spectra. It was found that all synthesized compounds exhibited moderate antimicrobial activity.

Synthesis and antimicrobial activity of 2-aroylmethylene-6-hydroxy-2,3-dihydroindol-3-ones

The interaction of methyl esters of aroylpyruvic acids with 2-aminophenol was used to form 2-aroylmethylene-6-hydroxy-2,3-dihydroindol-3-ones. The structures of these compounds were verified by IR and 1H NMR spectroscopy; the antimicrobial activity of the compounds synthesized here was studied.

Five-membered 2,3-dioxo heterocycles. 21. Reaction of 1,5-diaryl-4-ethoxycarbonyl-tetrahydropyrrole-2,3-diones with 2-aminopyridine

The reaction of 2-aminopyridine with 1,5-diaryl-4-ethoxycarbonyltetrahydropyrrole-2,3-diones gave 1∶1 complexes, which are converted to N-(2-pyridyl)-1,5-diaryl-3-hydroxy-2-oxo-2,5-dihydropyrrole-4-carboxamides when they are heated above their melting points without a solvent. The character of the hydrogen bonds in the complexes obtained is discussed.

Interaction of substituted 4-acylpyrrolin-2-ones with primary amines and the antimicrobial activity of the resulting compounds

Interaction of 1-(2-methoxyethyl)-5-aryl-4-acyl-3-hydroxy-3-pyrrolin-2-ones with aromatic amines such as p-toluidine, p-bromaniline, and p-anisidine and aliphatic amines such as butylamine and ethanolamine formed 5-aryl-4-aroyl-3-arylamino-1-(2-methoxyethyl)-3-pyrrolin-2-ones and 4-(1-R2-aminoethylene)-tetrahydropyrrol-2,3-diones. The antimicrobial activities of the resulting compounds were studied.