A. P. Kriven'ko

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF N,N-DIARYL-2-ARYL-6-HYDROXY-6-METHYL-4- OXOCYCLOHEXANE-1,3-DICARBOXAMIDES

A series of N,N′-diaryl-2-aryl-6-hydroxy-6-methyl-4-oxocyclohexane-1,3-dicarboxamides have been synthesized by the reaction of N-arylamides of acetoacetic acid with aromatic aldehydes in the presence of piperidine. The structures of the products were determined by IR, PMR, and mass spectroscopy. Data on the antimicrobial activity of the synthesized compounds are presented.

Synthesis and Antimicrobial Activity of 3-Aryl-5-hydroxy-5-methyl-2,4-di(methoxycarbonyl)cyclohexanones and Their Derivatives

It was reported [1] that the interaction of acetylacetic acid ethylate with aromatic aldehydes in the presence of a basic catalyst leads to the formation of 3-aryl-5-hydroxy5-methyl-2,4-di(ethoxycarbonyl)cyclohexanones. These compounds can react with aromatic amines to yield enamines [2], and with hydrazine and hyroxylamine to form heterocyclic systems possessing biological activity [3, 4]. In continuation of our previous investigations into the synthesis and characterization of cycloketones, we have reacted acetylacetic acid methylate with aromatic aldehydes, studied reactions of the products with aromatic amines, and evaluated the antimicrobial activity of the synthesized compounds. It was found that methylacetoacetate readily interacts with aromatic amines at room temperature in the presence of piperidine. The interaction leads to the formation of 2,4-di(methoxycarbonyl)-3-aryl-5-hydroxy-5-methylcyclohe xanones (I – XV). The course of these reactions depends on the nature of the substituents in the aromatic aldehyde. Electron-donor substituents (such as (C2H5)2N, CH3O, and C2H5O) in the para position hinder the interaction, whereby the product yield decreases down to 55 – 65%. In contrast, electron-acceptor substituents (e.g., NO2) in the para position facilitate the reaction and increase the yield up to 82%. A high yield (78 – 80%) is also observed in the case of a halogen atom in the para position with respect to the aldehyde group. This is probably related to the considerable contribution of the negative induction effect of the halogen atom to the electron density distribution in the ring. On the other hand, the presence of a halogen atom in the ortho position does not lead to a high yield; moreover, fluorine atom in the ortho po-

Synthesis and Antimicrobial Activity of Substituted 1,8-Dioxodecahydroacridines

Decahydroacridine-1,8-diones based structurally on a 1,4-dihydropyridine fragment possess a broad spectrum of pharmacological activity, including antimicrobial properties. However, data on the antimicrobial activity of these compounds are restricted to a few patents, which refer only to 9-aryl-N-carboxyalkyl-decahydroacridine-1,8-diones [1, 2]. In order to study the antimicrobial properties of NH-, N-methyl-, N-phenyl, and N-benzyl-decahydroacridine-1,8diones containing various pharmacophore groups in position 9, including 5-nitrofuryl, furyl, and thienyl, we synthesized a series of compounds (V – XIII) using a previously developed method based on the condensation of enaminoketones I – IV with aldehydes in a 20% P 2 O 5 solution in isopropyl alcohol [3, 4]:

Synthesis and biological activity of substituted 7-aza-8-aza(oxa)-bicyclo[4.3.0]-6,9-nonadienes

Hydroxylamine- and hydrazine-induced heterocyclization of readily available 5-hydroxy-2.4-diacetyl-5-methyl-3R-cyclohexanones (R = methyl, phenyl, m-nitrophenyl, α-furyl) yielded 6-acetyl-5-hydroxy-5.9-dimethyl-7R-1-aza(oxa)-2-azabicyclo[4.3.0]-2,8-nonadienes (R = methyl, phenyl,m-nitrophenyl. α-furyl). The biological activity of the latter was tested using theEscherichia coli phage T4, and was also tested on a stored lyophilized culture ofYersinia pestis EU.

Synthesis and stereochemistry of perhydroacridines (review)

Methods for the synthesis of isomeric perhydroacridines are reviewed. Their configurational and conformational features are discussed.

Synthesis and Antimicrobial Activity of 2,4-Dibenzyloxy(Diallyloxy)carbonyl-3-aryl-5-hydroxy-5-methylcyclohexanones

A series of 2,4-dibenzyloxy(diallyloxy)carbonyl-3-aryl-5-hydroxy-5-methylcyclohexanones have been obtained via reactions of benzylacetoacetate and allylacetoacetate with aromatic aldehydes in the presence of a basic catalyst (piperidine). The proposed structures are confirmed by the results of 1H NMR spectroscopy, IR absorption spectroscopy, and high-resolution mass spectrometry measurements. Data on the antimicrobial activity of the synthesized compounds are presented.

Synthesis of Substituted Hexahydroindazoles

Substituted hexahydroindazoles were obtained by the reaction of 6-arylidene-2-furfurylidene-cyclohexanones with phenylhydrazine. It was concluded by means of the NMR spectra that azacyclization takes place regioselectively with participation of the arylidenecyclohexanone fragment.

Synthesis and Antiphage Activity of Substituted N-Arylcyclohexenylamines

Substituted -cycloketols such as 3-R-2,4-diacetyl(diethoxycarbonyl)-5-hydroxy-5-methylcyclohexanone and related compounds exhibit a broad spectrum of biological activity [1 – 3]. Previously [4] we reported on the antiphage and cryoprotector properties of pyrazoles and isoxazoles synthesized by interaction of such -cycloketols with nitrogen-containing binucleophilic reagents [4]. Below we present data on the synthesis and antiphage properties of a series of previously obtained [5 – 7] and new cyclohexenylarylamines (VII – XVII) representing the products of arylamination of -cycloketols I – VI. The arylamination process was performed under acid catalysis conditions according to the scheme

Saturated Nitrogen-containing Heterocycles. 20. Catalytic Reduction of N-Hydroxyethylpyridinium and Quinolinium Salts

Previously unknown N-(2-hydroxyethyl)perhydroquinolines and N-(2-hydroxyethyl)piperidines were synthesized by catalytic reduction of N-(2-hydroxyethyl)tetrahydroquinolinium and N-(2-hydroxyethyl)tetrahydropyridinium tetrafluoroborates. A scheme for the formation of the hydrogenation products is presented.

Peculiarities of formation of decahydroacridine-1,8-diones on the basis of 1,3-dioxocyclohexane compounds in various media

The conditions for the formation of N-substituted decahydroacridine-1,8-diones from α-R-methylenebiscyclohexane-1,3-diones and 5,5-dimethyl-3-(N-methylamino)-2-cyclohexen-1-one in ethanol, isopropanol, and DMSO have been studied. Methods have been developed for preparation of 1,8-dioxo-10-methyldecahydroacridines which contain furyl and 5-nitrofuryl substituents at the 9 position.