The synthesis of azole derivatives from 3-[(4-methylphenyl)amino]propanehydrazide and its N′-phenylcarbamoyl derivatives, and their antibacterial activity

Abstract  

5-[2-[(4-Methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-thione, 5-[2-[(4-methylphenyl)amino]ethyl]-1,3,4-oxadiazol-2(3H)-one, N-(2,5-dimethyl-1H-pyrrol-1-yl)-3-[(4-methylphenyl)amino]propanamide, and a series of N-[(phenylcarbamoyl)amino]-3-[(4-methylphenyl)amino]propanamides and 3-[(4-methylphenyl)(phenylcarbamoyl)amino]-N-[(phenylcarbamoyl)amino]propanamides, and their thio analogues were synthesized from 3-[(4-methylphenyl)amino]propanehydrazide. 1,3,4-Oxadiazole-2(3H)-thione was converted to 4-amino-2,4-dihydro-5-[2-[(4-methylphenyl)amino]ethyl]-3H-1,2,4-triazole-3-thione, whereas cyclization of N′-phenylcarbamoyl derivatives provided thiazole, oxadiazoles, and thiadiazole, as well as triazole derivatives. Two of the synthesized compounds exhibited good antibacterial activity against Rhizobium radiobacter.     

Deoxypegan-1-one derivatives. synthesis and borohydride reduction of 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones

3-[(E)-Arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolin-1(2H)-ones were prepared by reaction of quinazolyl-2-propionic acid hydrochloride with aromatic aldehydes in acetic anhydride in the presence of Et₃N. 3-[(E)-Arylmethylidene]-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-1-ols were formed by reduction of the 3-arylidene derivatives with sodium borohydride in methanol, readily lost water when heated with acids, and were converted into 3-[(E)-arylmethylidene]-3,9-dihydropyrrolo[2,1-b]quinazolines. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 463–467, September–October, 2006.     

Synthesis of some substituted dibenzodiazepinones and pyridobenzodiazepinones

Some fluoro- and iodo-derivative of 5-[[4-[(4-diisobutylamino)butyl]-1-phenyl]acetyl]-10,11-dihydro-5H-dibenzo[b,e][1,4]diazepin-1l-one and 11-[[4-[(dialkylamino)butyl]-1-phenyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-ones 6 (Scheme 1) and their analogues were synthesized. The synthesis of dibenzodiazepinones 1 (Scheme 1) is based on the reaction between 1,4-phenylenediamine and substituted benzoic acids. The intermediate pyridobenzodiazepinones 3 (Scheme 1) were prepared by condensation of 2-chloro-3-aminopyridine with methyl anthranilate and its chlorine derivative. The condensation of 4-[(halo)alkyl]phenylacetyl chloride with dibenzodiazepinones and pyridobenzodiazepinones followed by the reaction of mono- or dialkyl- or dialkenylamine provides 6 (Scheme 1).     

A series of novel acyclic nucleosides. II. Synthesis of acyclic nucleosides bearing an imidazo[4,5-d] [1,3]oxazine ring

Novel acyclic nucleosides 3a,b,c where N-1 of acyclovir is replaced by oxygen atom were prepared. Thus, 1-[(2-acetoxyethoxy)methyl]-5-amino-4-ethoxycarbonylimidazole ( 9 ) was treated with ethoxycarbonyl isothiocyanate or benzoyl isothiocyanate to give 11e,f . Methylation of the latter with methyl iodide afforded S-methylisothiourea derivative 12f which was treated with alkali and subsequently the mixture was neutralized to give 5-amino-3-[(2-hydroxyethoxy)methyl]-3H-imidazo[4,5-d][1,3]oxazin-7-one ( 3a ). Compounds 3b,c were obtained by treatment of acetic anhydride or propionic anhydride with sodium 5-amino-1-[(2-hydroxyethoxy)methyl]imidazole-4-carboxylate ( 7 ) which was prepared via 5-amino-[(2-acetoxyethoxy)methyl]-imidazole-4-carboxamide ( 5 ). Evaluation of acyclic oxanosine analogs for cytotoxicity and activity against herpes simplex virus type 1 (HSV-1) revealed that all the derivatives tested were inactive, but cytotoxicity were similar or less as compared to that of acyclovir.     

Synthesis of antimicrobial agents. II. Syntheses and antibacterial activities of optically active 7-(3-hydroxypyrrolidin-1-yl)quinolones

Two optically active isomers of 1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-hydroxypyrrolidin-1-yl)-4-oxoquinoline-3-carboxylic acid ( 10 ) were prepared. One of the isomer, 7-[(3S)-hydroxypyrrolidin-1-yl] derivative 8 , was about 4 times more potent in vitro than the other, 7-[(3R)-hydroxypyrrolidin-1-yl] derivative 4 , and approximately two times more active than the racemate, 7-[(3RS)-hydroxypyrrolidine-1-yl] derivative 10. Optical active 8 was the most active in in vivo, followed by 10 , and 4 was the least active compound. But, they were more potent than CI-934 12 and norfloxacin. From the results, (3S)-hydroxypyrrolidinyl group was found to be one of the beneficial group for PCA-anti-bacterial agent.     

Synthesis of New 2-[(Substituted-pyrazolin-1-yl)carbonyl]-thieno[2,3-b]pyridine Derivatives

The reaction of 3-amino-4,6-dimethyl-2-thieno[2,3-b]pyridine carbohydrazide ( 1 ) with appropriate chalcones 2a-2d in the presence of acid catalyst produced the corresponding 3-amino-2-[(3,5-disubstituted-pyrazolin-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 3a-3d . 3-Amino-2-[(3-substituted-pyrazolin-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 7a, 7b were also obtained by the cyclization reaction of carbohydrazide 1 with Mannich base derivatives 6a, 6b under basic condition.     

Regioselective hydrolysis of ketenimines derived from NH-acids and acetylenic esters in the presence of tert -butyl isocyanide under neutral conditions

The regioselective hydrolysis of ketenimines derived from NH-acids, such as 2,2,2-trichloro-N-phenylacetamide or ethyl-2-anilino-2-oxoacetates and acetylenic esters in the presence of tert-butyl isocyanide in a THF/H₂O system (1/1) without any catalysis leads to a diastereomeric mixture of dialkyl 2-[(tert-butylamino)carbonyl]-3-[(2,2,2-trichloroacetyl)anilino]succinates and dialkyl 2-[(tert-butylamino)carbonyl]-3-[2-ethoxy-2-oxoacetyl)anilino]-succinates in good yields. Dynamic NMR effects were observed in the ¹³C NMR spectra of diethyl 2-[(tert-butylamino)carbonyl]-3-[(2,2,2-trichloroacetyl)anilino]succinate as a result of restricted rotation around the N-aryl single bond. The free energy of activation (ΔG ^#) for this process is 37.9 kJ mol⁻¹ which leads to an observable atropisomerism.     

Synthesis of New 2-[(Substituted-pyrazol-1-yl)carbonyl]-thieno[2,3b]pyridine Derivatives Using 1,3-Diketones,Alkylethoxymethylenes and Ketene Dithioacetals

The reaction of 3-amino-4,6-dimethyl-2-thieno[2,3-b]pyridine carbohydrazide ( 1 ) with appropriate 1,3-diketones 2a-2d in glacial acetic acid afforded 3-amino-2-[(3,5-disubstituted-pyrazo)-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 3a-3d. 3-Amino-2-[(5-amino-3,4-disubstituted-pyrazol-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 5a-5h were also prepared by treatment of carbohydrazide 1 with appropriate alkylethoxymethylenes and ketene dithioacetals 4a-4h , respectively.     

Regioselective hydrolysis of ketenimines derived from NH-acids and acetylenic esters in the presence of <Emphasis Type="Italic">tert</Emphasis>-butyl isocyanide under neutral conditions

The regioselective hydrolysis of ketenimines derived from NH-acids, such as 2,2,2-trichloro-N-phenylacetamide or ethyl-2-anilino-2-oxoacetates and acetylenic esters in the presence of tert-butyl isocyanide in a THF/H₂O system (1/1) without any catalysis leads to a diastereomeric mixture of dialkyl 2-[(tert-butylamino)carbonyl]-3-[(2,2,2-trichloroacetyl)anilino]succinates and dialkyl 2-[(tert-butylamino)carbonyl]-3-[2-ethoxy-2-oxoacetyl)anilino]-succinates in good yields. Dynamic NMR effects were observed in the ¹³C NMR spectra of diethyl 2-[(tert-butylamino)carbonyl]-3-[(2,2,2-trichloroacetyl)anilino]succinate as a result of restricted rotation around the N-aryl single bond. The free energy of activation (ΔG ^#) for this process is 37.9 kJ mol⁻¹ which leads to an observable atropisomerism. Correspondence: Dr. Farough Nasiri PhD, Department of Chemistry, Faculty of Sciences, University of Kurdistan, P.O. Box 66315-416, Sanandaj, Iran.     

Synthesis, 1H- and 13C-NMR spectra,crystal structure and ring openings of 1-methyl-6,9-epoxy-9-aryl-5,6,9,10-tetrahydro-1H-imidazo [3,2-e] [2H-1,5] oxazocinium methanesulfonate

The methanesulfonic acid catalyzed reaction of 1-(4-chloro- and 2,4-dichlorophenyl)-2-(1-methyl-2-imida-zolyl)ethanones 1a and 1b with glycerol produced cis- and trans-{2-haloaryl-2-[(1-methyl-2-imidazolyl)methyl]-4-hydroxymethyl}-1,3-dioxolanes 2a and 2b with a 2:1 cis/trans ratio. Besides these five-membered ketals, the reaction of 1a with glycerol afforded a small amount of trans-{2-(4-chlorophenyl)-2-[(1-methyl-2-imidazolyl)methyl]-5-hydroxy}-1,3-dioxane ( 3a , 7%). The reaction of methanesulfonyl chloride with cis-1 formed the corresponding methanesulfonates, cis- 4 , which rapidly cyclized to the title compounds 5 . Base-catalyzed ring opening of 5 furnished 1-methyl-5,6-dihydro-6-hydroxymethyl-8-(4-chloro- and 2,4-dichlorophenyl)-1H-imidazo[3,2-d][1,4]oxazepinium methanesulfonates 7 . Acid-catalyzed hydrolyses of 5 or 7 provided 1-methyl-2-[(4-chloro- and 2,4-dichloro)phenacyl]-3-[(2,3-dihydroxy)-1-propyl]imidazolium salts 12 . Structure proofs were based on extensive ¹H and ¹³C chemical shifts and coupling constants and structures of 3a and 5a were confirmed by single crystal X-ray crystallography.     

Syntheses of Novel Nonreducing-Sugar Subunit Analogs of Lipid a Carrying 2-Acyloxytetradecanoyl and 2-Hydroxyacyl Groups of Different Carbon Chain Length

Abstract

To investigate the biological influence of the 2-(acyloxy)tetradecanoyl and 2-hydroxyacyl groups in the nonreducing-sugar subunit analogs of lipid A, a novel series of 3-(O-[(2RS)-2-acyloxytetradecanoyl]-2-deoxy-2-[(2RS)-2-hydroxytetradecanamido]-4-O-phosphono-d-glucoses (10a-d), 3-O-[(2RS)-2-acyloxytetradecanoyl]-2-deoxy-2-[(3R)-3-hydroxytetradecanamido]-4-O-phosphono-d-glucoses (19a-d), and 2-deoxy-2-[(2RS)-2-hydroxyacyl]amino-4-O-phosphono-3-O-[(3R)-3-tetradecanoyloxytetradecanoyl]-d-glucoses (23e-h) were systematically synthesized.     

Synthesis and urease inhibition studies of some new quinazolinones

In this study, novel quinazolinones were designed, synthesized, characterized by FT-IR, ¹H-NMR, ¹³C-NMR spectral data, and LC–MS. New compounds inhibitory activities on urease were assessed. All of the compounds exhibited potent urease inhibitory activities. Especially in the synthesized compounds, 2-benzyl-3-({5-[(4-nitrophenyl)amino]-1,3,4-thiadiazol2-yl}methyl)quinazolin-4(3H)-one has the best inhibitory effect against Jack bean urease with IC₅₀ = 3.30 ± 0.09 μg/mL. And also, N-(4-nitrophenyl)-2-[(4-oxoquinazolin-3(4H)-yl)acetyl] hydrazinecarbothioamide, N-(4-fluorophenyl)-2-[(4-oxoquinazolin-3(4H)-yl)acetyl] hydrazinecarbothioamide, and 2-benzyl-3-({5-[(4-fluorophenyl)amino]-1,3,4-thiadiazol-2yl} methyl)quinazolin-4(3H)-one have best activities among the synthesized compounds.     

Synthesis,structures, and photochromic properties of 3-[(<Emphasis Type="Italic">E</Emphasis>)-alk-1-enyl]-4-(1-alkyl-5-methoxy-2-methyl-1<Emphasis Type="Italic">H</Emphasis>-indol-3-yl)furan-2,5-diones

New hetarylethenes, viz., 3-[(E)-alk-1-enyl]-4-(1-alkyl-5-methoxy-2-methyl-1H-indol-3-yl)furan-2,5-diones, exhibiting photochromic properties in solution were synthesized. The molecular and crystal structure of 3-(5-methoxy-1,2-dimethyl-1H-indol-3-yl)-4-[(E)-prop-1-enyl]furan-2,5-dione was determined by X-ray diffraction. The initial and photoinduced forms of hetarylethenes are characterized by thermal stability. The open-ring isomers of furandiones exhibit fluorescence with quantum yields of up to 0.1.     

Synthesis of 4-acetylcolchicine

The synthesis of 4-acetylcolchicine ( 1 ) by Swern dehydrogenation of the corresponding mixture of 4-[(R)-1-hydroxyethyl]- and 4-[(S)-1-hydroxyethyl]colchicine ( 3a and 3b , respectively) is described (cf. Scheme). The X-ray analysis of 1 (cf. Fig.), crystallized from MeOH, showed the presence of MeOH in the crystals.     

Poly[(3-hydroxypropyl) oxirane] and poly[(4-hydroxybutyl)oxirane]: New hydrophilic polyether elastomers

Preparations of poly[(3-hydroxypropyl)oxirane] and poly[(4-hydroxybutyl)oxirane] are described. Three routes to poly[(3-hydroxypropyl)oxirane] are discussed, each of which involves the methanolysis of a polymeric ester. (3-Acetoxypropyl)oxirane, [3-(m-chlorobenzoyloxy)propyl]oxirane, and (3-chloropropyl)oxirane were polymerized using the AIEt₃/H₂O/AcAc initiator system. Poly[(3-acetoxypropyl)oxirane] and poly{[3-(m-chlorobenzoyloxy)propyl]oxirane} were converted directly to poly[(3-hydroxypropyl)oxirane] by methanolysis, the former under either acidic or basic conditions only. Poly[(3-chloropropyl)oxirane] was first converted to poly[(3-benzoyloxypropyl)oxirane] by treatment with tetrabutylammonium benzoate; subsequent basic methanolysis then afforded poly[(3-hydroxypropyl)oxirane]. Poly[(3-hydroxypropyl)oxirane] is a colorless elastomer which can be cast into tough, clear films from water or methanol. Poly[(4-hydroxybutyl)oxirane] was prepared from poly[(4-chlorobutyl)oxirane] by benzoyloxylation and subsequent methanolysis. Poly[(4-hydroxybutyl)oxirane] is insoluble in water, but is hydrophilic and can be cast into tough films from methanol or dimethylsulfoxide.     

A Novel,Degraded Polyketidic Lactone,Leptosphaerolide, and Its Likely Diketone Precursor,Leptosphaerodione. Isolation from Cultures of the Marine Ascomycete Leptosphaeria oraemaris (LINDER)

Acetone extraction of cultures of the marine ascomycete Leptosphaeria oraemaris (LINDER) on cornmeal disk gave the novel polyketide derivative leptosphaerolide ( = (+)-7-[(1E)-l,3-dimethylpent-1-enyl]-10-hydroxy-3-methoxybenzo[1,2-b:5,4-c′]dipyran-2(9H)-one; (4+)-8) besides the o-dihydroquinone 3-[(1E)-1,3-dimethylpent-1-euyl]-8,10-dihydroxy-7-methoxy-8-(2-oxopropyl)-1H-naphtho[2,3-c]pyran-9(8H)-one ( 1 ) as a 10:9 mixture of epimers. retro-Aldol reaction of 1 gave leptosphaerodione ( = (?)-3-[(1E)-1,3-dimethylpent-1-enyl]-10-hydroxy-7-methoxy-1H-naphtho[2,3-c]pyran-8,9(8H)-dione; (?)-6) which was also present in small amounts in the extracts and which gave 1 on reaction with acetone. It is thus likely that 1 is an artefact of the extraction by acetone. Biogenetically (+)-8 might derive from (?)-6 via an unusual oxidation with loss of CO₂.     

Poly(β-Amino acids). VI. Synthesis and conformational properties of poly[(r)-3-pyrrolidinecarboxylic acid]

Racemic and optically active 3-pyrrolidinecarboxylic acids (β-proline) were synthesized, and their polymers, poly[(RS)-β-proline] and poly[(R)-β-proline], were prepared by the polycondensation reaction of the p-nitrophenyl esters. Model compounds, N-cyclopentylcarboxylic acid pyrrolidide and N-cyclopentylcarbonyl-(R)-3-pyrrolidinecarboxylic acid pyrrolidide, were synthesized to elucidate the conformation of the polymer. The solution properties of poly[(R)-β-proline] and the model compounds were investigated by means of circular dichroism (CD) and NMR spectroscopy. The spectral patterns of the polymer and model compounds were similar in various solvents. Poly[(R)-β-proline] and poly[(RS)-β-proline] showed identical NMR spectra. These results suggest that poly[(R)-β-proline] may exist in a random conformation consisting of mixtures of cis and trans amide bonds. The conformational study of cyclopentanecarboxylic acid pyrrolidide by NMR spectroscopy with a shift reagent, Eu(fod)₃, in CDCl₃ implied that the plane containing the amide group bisects the cyclopentane ring. This suggests that each amide plane in the polymer in chloroform may also bisect the pyrrolidine ring.     

Amidines: synthesis from o-alkenylanilines and cyclization in polyphosphoric acid

Condensation of 2-[(E)-pent-3-en-2-yl]-4-, 2-[(E)-pent-2-en-2-yl]-4-, or 2-(cyclopent-1-enyl)-6-methylaniline with 1-chloro-1-(N-methylimino)- or 1-chloro-1-(N-phenylimino)ethane affords the corresponding amidines. Cyclization of the N-methylimino derivatives in polyphosphoric acid gives 3,4-dihydroquinazolines in high yields.     

Reactions of Elemental Phosphorus and Phosphine with Electrophiles in Superbasic Systems: XV. Phosphorylation of Allyl Halides with Elemental Phosphorus

Elemental phosphorus (red or white) reacts with allyl chloride and allyl bromide in a two-phase system aqueous KOH-organic solvent to form tertiary symmetrical and mixed phosphine oxides among which tris(prop-2-enyl)-, bis(prop-2-enyl)[(E)-prop-1-enyl]-, bis(prop-2-enyl)[(Z)-prop-1-enyl]-, (prop-2-enyl)[(E)-prop-1-enyl][(Z)-prop-1-enyl]-, bis[(E)-prop-1-enyl](prop-2-enyl)-, bis[(Z)-prop-1-enyl](prop-2-enyl)-, tris-[(E)-prop-1-enyl]-, and bis[(E)-prop-1-enyl][(Z)-prop-1-enyl]phosphine oxides were identified. The conditions (room temperature, 60% aqueous KOH-dioxane) allowing preparation from white phosphorus and allyl bromide of tris(prop-2-enyl)- and bis(prop-2-enyl)[(E)-prop-1-enyl]phosphine oxides as major products in the total yield of up to 96% were found.     

Chiral exo-Alkylidenecyclopentanes from (1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one

(1S,4R)-7,7-Dimethyl-1-vinylbicyclo[2.2.1]heptan-2-one oxime in the system (CF₃CO)₂O-CF₃COOH and (1S,4R)-1-(1,2-dibromoethyl)-7,7-dimethylbicyclo[2.2.1]heptan-2-one in the system MeONa-MeOH undergo fragmentation to give exo-alkylidenecyclopentane derivatives, (4R)-4-cyanomethyl-5,5-dimethyl-1-[(1E)-trifluoroacetoxyethylidene]cyclopentane and isomeric (4R)-4-carboxymethyl-1-[(1ZE)-2-methoxyethylidene]-5,5-dimethylcyclopentanes, respectively. The trifluoroacetate derivative undergoes unusual rearrangement, yielding an equilibrium mixture of two isomers with endo- and exocyclic double bond.