<Emphasis Type="Italic">S</Emphasis>-functional derivatives of 3,4-dihydro-2<Emphasis Type="Italic">H</Emphasis>-1,4-thiasilines

The first cyclic unsaturated S-functional derivatives of 4,4-diphenyl-3,4-dihydro-2H-1,4-thiasiline, S-oxide, S,S-dioxide, and S-sulfonimide, were prepared. Oxidation of the hydrolytically less stable 4,4-dimethyl-3,4-dihydro-2H-1,4-thiasiline leads to the corresponding sulfoxide and sulfone along with the ring opening products, siloxanes containing the sulfoxide or sulfonyl group.     

Synthesis of 4<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbaldoxime 3-oxides and 4<Emphasis Type="Italic">H</Emphasis>-imidazole-5-carbonitrile 3-oxides

The condensation of 3-hydroxyamino-3-methylbutan-2-one or 3-ethyl-3-hydroxyamino-pentan-2-one with aldehydes and ammonia afforded a series of new 1-hydroxy-4-methyl-2,5-dihydroimidazoles, whose oxidation gave rise to the corresponding 5-methyl-4H-imidazole 3-oxides. The latter, like 1-hydroxy-4-methyl-2,5-dihydroimidazoles, react with PrⁱONO in the presence of bases to form 4H-imidazole-5-carbaldoxime 3-oxides, which are transformed into 4H-imidazole-5-carbonitrile 3-oxides in the reaction with TsCl in the presence of Et₃N. The by-products produced in different steps of the synthesis were isolated and characterized. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1487–1503, July, 2008.     

Synthesis and antimicrobial screening of novel 9-{2-[(1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazol-4-yl)methoxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1<Emphasis Type="Italic">H</Emphasis>-xanthene-1,8(2<Emphasis Type="Italic">H</Emphasis>)-dione derivatives

A series of novel 9-{2-[(1H-1,2,3-triazol-4-yl)methoxy]phenyl}-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione derivatives were synthesized by a click chemistry approach. The structures of all the newly synthesized compounds were characterized by IR, MASS, ¹H and ¹³C NMR spectral data. The final analogues showed good to excellent antibacterial and antifungal activities in an agar well diffusion assay. Compounds 6i and 6f were the most active against all the test bacterial and fungal strains.     

Synthesis and antimicrobial activity of 2<Emphasis Type="Italic">H</Emphasis>-pyrimido[2,1-<Emphasis Type="Italic">b</Emphasis>]benzothiazol-2-ones

4-Phenyl-2H-pyrimido[2,1-b]benzothiazol-2-ones have been synthesized in quantitative yields by the reaction of 2-aminobenzothiazoles with alkynoic acid. The antimicrobial activity of the synthesized compounds was tested against bacterial species, Bacillus coagulans, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. The synthesized compounds have shown significant activity against microorganisms which can be correlated with the fused heterocyclic systems.     

Synthesis and biotests of 2-aryl-5-arylmethylidene-substituted 1,3-oxazol-5(4<Emphasis Type="Italic">H</Emphasis>)-ones and <Emphasis Type="Italic">N</Emphasis>-methyl-3,5-dihydro-4<Emphasis Type="Italic">H</Emphasis>-imidazol-4-ones as combretastatin A-4 analogs

A series of 2-aryl-5-arylmethylidene-1,3-oxazol-5(4H)-ones and 2-aryl-5-arylmethylidene-N-methyl-3,5-dihydro-4H-imidazol-4-ones was synthesized as structural analogs of combret- astatin A-4 (a compound possessing antitumor activity). (5Z)-5-[(4-Methoxyphenyl)methyl-idene]-3-methyl-2-(4-methylphenyl)-3,5-dihydro-4H-imidazol-4-one was found to exhibit the highest cytotoxicity against cells of human A549 lung carcinoma line (EC₅₀ = 6±0.8 μmol L^?1).     

Synthesis and study of macroheterocyclic compounds derived from 1<Emphasis Type="Italic">H</Emphasis>-phenalene-1,3(2<Emphasis Type="Italic">H</Emphasis>)-diimine

Symmetrical macroheterocyclic compounds are synthesized by the reaction of 1H-phenalene-1,3(2H)-diimine with m-phenylenediamine, 2,6-diaminopyridine, and 2,5-diamino-1,3,4-thiadiazole. IR and UV spectral data are given.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 8, 2004, pp. 1355–1359.Original Russian Text Copyright © 2004 by Berezina, Vorobev, Vorobeva, Andreikina.This revised version was published online in April 2005 with a corrected cover date.     

Synthesis and antibacterial activity of new <Emphasis Type="Italic">N</Emphasis>-substituted 7-amino-4-methyl-2<Emphasis Type="Italic">H</Emphasis>-chromen-2-ones

N-Substituted 7-amino-4-methyl-2H-chromen-2-ones containing one or two functionalized azole or azine moieties were synthesized. The structures of all synthesized compounds were confirmed by IR, ¹H NMR, and ¹³C NMR spectroscopy. Some of the synthesized compounds exhibited weak antibacterial activity against Rhizobium radiobacter, Escherichia coli, and Xanthomonas campestris.     

Synthesis of carbamate derivatives of 2,3-dihydro-4<Emphasis Type="Italic">H</Emphasis>-1,4-benzoxazine

Alkylation of methyl 2-hydroxyphenylcarbamates with 1,2-dibromoethane in acetone in the presence of K₂CO₃ gave the corresponding methyl 6(7)-R-2,3-dihydro-4H-1,4-benzoxazine-4-carboxylate. Alkylation of methyl 2-hydroxyphenylcarbamates with chloromethyloxirane was accompanied by recyclization of the oxirane ring with formation of methyl 6(7)-R-3-hydroxymethyl-2,3-dihydro-4H-1,4-benzoxazine-4-carboxylates.     

Tautomerism of azacycles: III. Molecular and crystal structures of 3<Emphasis Type="Italic">H</Emphasis>-and 2-phenyl-1<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>-4,5-dihydro-1,2,4-triazole-5-thiones

Compounds capable of tautomerism: sulfanyl-1,2,4-triazole, its C-phenyl derivative, and the crystal hydrate of the latter, were studied by single crystal X-ray diffraction. In the crystals they exist in the form of 3-R-1(H),4(H)-4,5-dihydro-1,2,4-triazole-5-thione with a considerable contribution of the bipolar structure. Published data on the tautomerism of sulfanyl-1,2,4-triazoles and their N-substituted analogs and on the correlation between the spectral characteristics and structures of sulfanyl-1,2,4-triazoles capable of tautomerism are discussed.     

Synthesis of novel 4<Emphasis Type="Italic">H</Emphasis>-furo[3,2-c]pyran-4-ones and 4<Emphasis Type="Italic">H</Emphasis>-furo[3,2-<Emphasis Type="Italic">c</Emphasis>]chromen-4-ones

It was found that the condensation of two equivalents of 4-hydroxy-6-methyl-2H-pyran-2-one or 4-hydroxycoumarin with arylglyoxals in boiling formic acid leads to 4H-furo[3,2-c]-pyran-4-ones or 4H-furo[3,2-c]chromen-4-ones, respectively.     

Synthesis of amino acid conjugates of glycyrrhizic acid using <Emphasis Type="Italic">N</Emphasis>-hydroxyphthalimide and <Emphasis Type="Italic">N</Emphasis>,<Emphasis Type="Italic">N</Emphasis>'-dicyclohexylcarbodiimide

Synthesis of amino acid conjugates of glycyrrhizic acid with the use of N-hydroxyphthalimide, N,N'-dicyclohexylcarbodiimide, and tert-butyl esters of L-amino acids (valine, isoleucine, phenylalanine, and methionine) was performed followed by deprotection with trifluoroacetic acid. The target amino acid conjugates were isolated by column chromatography on silica gel in 40–45% yield. The structure of the prepared compounds was confirmed by IR and ¹³C NMR spectroscopy.     

Synthesis of ethyl (2<Emphasis Type="Italic">E</Emphasis>,4<Emphasis Type="Italic">E</Emphasis>)- and (2<Emphasis Type="Italic">E</Emphasis>,4<Emphasis Type="Italic">Z</Emphasis>)-5-chloropenta-2,4-dienoates

An efficient synthetic approach to 2E,4E and 2E,4Z isomers of ethyl 5-chloropenta-2,4-dienoate has been developed on the basis of one-pot oxidation–olefination of readily accessible (E)- and (Z)-3-chloroprop-2-en-1-ols by the action of barium manganate and ethyl (triphenyl-λ⁵-phosphanylidene)acetate.     

Synthesis of 6-methyl-8<Emphasis Type="Italic">H</Emphasis>-dibenzo[<Emphasis Type="Italic">a</Emphasis>,<Emphasis Type="Italic">g</Emphasis>]quinolizin-8-imines <Emphasis Type="Italic">via Reissert</Emphasis> compounds

Alkylation of Reissert compounds derived from 3-methylisoquinolines with several 2-cyanobenzylbromides followed by hydrolytic cleavage provided the corresponding 1-benzyl-3-methylisoquinolines. Treatment of the latter with methylmagnesiumiodide caused cyclization to the title compounds rather than formation of 2-acetylbenzylisoquinolines.     

2-Imino 2<Emphasis Type="Italic">H</Emphasis>-chromene and 2-(phenylimino) 2<Emphasis Type="Italic">H</Emphasis>-chromene 3-aryl carboxamide derivatives as novel cytotoxic agents: synthesis,biological assay,and molecular docking study

The inhibition of AKR₁B₁₀ has been recognized as a potential therapeutic approach to the treatment of various types of cancers. A novel series of compounds with imino-2H-chromen and phenylimino-2H-chromen scaffolds were synthesized by Knoevenagel condensation reaction. The in vitro cytotoxic activity of synthesized compounds was evaluated against MOLT-4 and SK-OV-3 cells. Among the tested compounds, N-(3,4-dimethoxyphenyl)-2-(phenylimino)-2H-chromene-3-carboxamide (8g) demonstrated potent inhibitory activity against both examined cell lines. The results of the molecular docking study suggested that this compound is involved in critical hydrogen-bonding interactions with the Val301 and Lue302 of AKR₁B₁₀ catalytic site.     

Synthesis of substituted 3,4-dihydropyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones and pyrimidin-2(1<Emphasis Type="Italic">H</Emphasis>)-ones by the Biginelli reaction with 3,5-Di-<Emphasis Type="Italic">tert</Emphasis>-butyl-4-hydroxybenzaldehyde

Three-component acid-catalyzed cyclocondensation of 3,5-di-tret-butyl-4-hydroxybenzaldehyde with urea and ethyl acetoacetate or α-nitroacetophenone (Biginelli reaction) under homogeneous conditions gave the corresponding 5-substituted 3,4-dihydropyrimidin-2(1H)-ones having in position 4 of the heteroring an aryl substituent with sterically shielded hydroxy group. The condensation catalyzed by inorganic salts (Fe³⁺, Co²⁺, Zn²⁺, Li⁺) was successful only with ethyl acetoacetate as initial methylene-active component. Under analogous conditions, acetophenone and 4-fluoroacetophenone gave rise to 4,6-diarylpyrimidin-2(1H)-ones which are capable of undergoing phenol-quinonemethide tautomerism.     

7,8,9-trimethyl-1-phenyl-3<Emphasis Type="Italic">H</Emphasis>-pyrrolo[2,1-<Emphasis Type="Italic">d</Emphasis>][1,2,5]triazepin-4(5<Emphasis Type="Italic">H</Emphasis>)-one. Synthesis and reactions

A strategy was developed for the synthesis of 7,8,9-trimethyl-1-phenyl-3H-pyrrolo[2,1-d][1,2,5]-triazepin-4(5H)-one, reactions of its functionalization at the С⁴ atom and aza rings fusion at the С⁴?N³ bond were explored. The formation mechanism of the pyrrolo-1,2,5-triazepinone scaffold was suggested.     

Recyclization of 1,3-dialkyl-6-nitro-1<Emphasis Type="Italic">H</Emphasis>-imidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine-2,5(3<Emphasis Type="Italic">H</Emphasis>,4<Emphasis Type="Italic">H</Emphasis>)-diones into imidazole derivatives

Treatment of 5-amino-1,3-dialkyl-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones with sodium nitrite in aqueous HCl gave 1,3-dialkyl-1H-imidazo[4,5-b]pyridine-2,5(3H,4H)-diones which were nitrated with potassium nitrate in sulfuric acid to 6-nitro derivatives, and the latter underwent recyclization into 4-amino-1,3-dialkyl-5-(1H-pyrazol-5-yl)-2,3-dihydro-1H-imidazol-2-ones by the action of hydrazine hydrate.     

Reaction 5-(Arylmethylidene)pyrimidine-2,4,6(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>,5<Emphasis Type="Italic">H</Emphasis>)-triones with L-Proline and Aldehydes

Boiling in toluene of 5-(arylmethylidene)pyrimidine-2,4,6(1H,3H,5H)-triones with L-proline and aldehyde led to the formation of previously unknown substituted 1′-arylhexahydro-1H-spiro[pyrimidine-5,2′-pyrrolysine]-2,4,6(1H,3Н,5Н)-triones.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-aryl-2-methyl-4-oxo-3,4,5,6-tetrahydro-2<Emphasis Type="Italic">H</Emphasis>-2,6-methano-1,3,5-benzoxadiazocine-11-carboxamides

N-Aryl-2-methyl-4-oxo-3,4,5,6-tetrahydro-2H-2,6-methano-1,3,5-benzoxadiazocine-11-carboxamides were synthesized by three-component reactions of N-aryl-3-oxobutanamides with salicylaldehyde and urea in ethanol in the presence of NaHSO₄ as catalyst. The product structure was determined by IR and ¹H NMR spectroscopy and X-ray analysis.