Synthesis of 4-hydroxy-3-[(E)-2-(6-substituted-9H-purin-9-yl)vinyl]coumarins as lipoxygenase inhibitors

The synthesis of 4-hydroxy-3-[(E)-2-(6-substituted-9H-purin-9-yl)vinyl] coumarins has been achieved from the reactions of 4-hydroxycoumarin with 2-(6-substituted-9H-purin-9-yl)acetaldehydes in DMF under heating. The new compounds showed significant lipoxygenase inhibitory activity (e.g., 6a: IC₅₀ = 6.25 μM).     

Synthesis,biological evaluation and Structure Activity Relationships (SARs) study of 8-(substituted)aryloxycaffeine

A series of 8-(substituted)aryloxycaffeine were prepared from 8-bromocaffeine and (substituted)phenols by modified Ullmann reaction. In vitro antibacterial activity, inhibitory activity on topoisomerase II and pharmacological activities were evaluated for the synthesized 8-(substituted)aryloxycaffeine. Among the synthesized compounds, 8-(5-chloropyridin-3-yloxy)caffeine (3k) showed strong inhibitory activity (MIC = 15.6 μg/mL) against the tested gram negative (−) bacteria Salmonella enteritidis. 8-(quinolin-8-yloxy)caffeine (3g) showed the strongest inhibitory activity against topoisomerase II. And the compounds 8-(6-methylpyridin-2-yloxy)caffeine (3j) and 8-(3-chloro-6-(trifluoromethyl)pyridin-2-yloxy)caffeine (3m) showed analgesic effect without the central nervous system stimulation.     

Synthesis,anti-inflammatory and analgesic activity of 2-[4-(substituted benzylideneamino)-5-(substituted phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid derivatives

The title compounds 3a–l have been synthesized by the reaction of thiocarbohydrazide with substituted phenoxy acetic acid to obtained substituted 1,2,4-triazoles (1). Compound 1 was treated with various substituted aromatic aldehydes which results in 4-(substituted benzylideneamino)-5-(substituted phenoxymethyl)-2H-1,2,4-triazol-3(4H)-thiones (2a–g), further 2a–g is converted to 2-[4-(substituted benzylideneamino)-5-(substituted phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid (3a–l) derivatives by the reaction with chloroacetic acid. All the newly synthesized compounds were evaluated for in vivo anti-inflammatory and analgesic activities. Among the series 2-[4-(2,4-dichlorobenzylideneamino)-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid (3d), 2-[4-(4-dichlorobenzylideneamino)-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl thio] acetic acid (3e), 2-[4-(2,4-dichlorobenzylideneamino)-5-[(2,4-dichlorophenoxy)methyl]-4H-1,2,4-triazol-3-yl thio] acetic acid (3j) and 2-[5-[(2,4-dichlorophenoxy)methyl)]-4-(4-chlorobenzylideneamino)-4H-1,2,4-triazol-3-yl thio] acetic acid (3k) showed significant anti-inflammatory activity with P < 0.001 (63.4%, 62.0%, 64.1% and 62.5% edema inhibition, respectively), as compared to the standard drug diclofenac (67.0%) after third hour respectively and also compounds 3j, 3k exhibited significant analgesic activity with P < 0.001 (55.9% and 54.9% protection, respectively) and less ulcerogenic activity as compared with standard drug aspirin (57.8%).     

Preparation of various enantiomerically pure (benzotriazol-1-yl)- and (benzotriazol-2-yl)-alkan-2-ols

(S)-(−)-(Benzotriazol-1-yl)- and (S)-(−)-(benzotriazol-2-yl)-alkan-2-ols 7a–9a, 7b–9b and their (R)-(+)-acetates 10a–12a and 10b–12b were prepared in high enantiomeric excess via lipase from Pseudomonas fluorescens (Amano AK) catalyzed enantioselective acetylation of racemic alcohols 4a–6a and 4b–6b with vinyl acetate in tert-butyl methyl ether or toluene at 23 °C. The enantioselectivity of this transformation was dependent on the length of the alkyl chain with E-values ranging from 30 to 57. Several benzotriazole substituted ketones 1a–3a and 1b–3b were synthesized from 1H-benzotriazole and corresponding haloketones. These compounds were stereoselectively reduced with Baker’s yeast in water or in organic solvent containing 5% v/v of water at 30 °C to give the (S)-(−)-alcohol. Better stereoselectivity was observed in the kinetic resolution of racemic alcohols 4a–6a and 4b–6b (ee = 69–92% at 44–52% conversion) compared to reduction of corresponding prochiral ketones 1a–3a and 1b–3b with Baker’s yeast (ee = 40–67% at 39–89% conversion). Enhanced enantioselectivities were observed at lower temperatures.     

Reactions of (1R,2S)-1,2-di(2-furyl)-1,2-di(3-guaiazulenyl)ethane and (1R,2S)-1,2-di(3-guaiazulenyl)-1,2-di(2-thienyl)ethane with tetracyanoethylene (TCNE) in benzene: comparative studies on the products and their spectroscopic properties

Reactions of the title meso forms, (1R,2S)-1,2-di(2-furyl)-1,2-di(3-guaiazulenyl)ethane (1) and (1R,2S)-1,2-di(3-guaiazulenyl)-1,2-di(2-thienyl)ethane (2), with a two molar amount of TCNE in benzene at 25 °C for 5 h (for 1) and 48 h (for 2) under oxygen give new compounds, 2,2,3,3-tetracyano-4-(2-furyl)-8-isopropyl-6-methyl-1,4-dihydrocyclohepta[c,d]azulene (3) and 2,2,3,3-tetracyano-8-isopropyl-6-methyl-4-(2-thienyl)-1,4-dihydrocyclohepta[c,d]azulene (4), respectively, in 74 and 21% isolated yields. Comparative studies on the above reactions as well as the spectroscopic properties of the unique products 3 and 4, possessing interesting molecular structures, are reported and, further, a plausible reaction pathway for the formation of these products is described.     

Synthesis and biological evaluation of some novel-3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines

<正>The synthesis of a new series of 3-(5-substituted benzimidazol-2-yl)-5-arylisoxazolines(6a-h) was achieved in excellent yields by the condensation of 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones(5a-h) with hydroxylamine at room temperature.These 1-(1H-benzimidazol-2-yl)-3-(substituted phenyl)prop-2-en-1-ones(5a-h) were obtained by the condensation of 2-acetyl benzimidazoles(4a-d) with different aromatic aldehydes,which in turn were obtained by the oxidation of 2-(α-hydroxy) ethyl benzimidazoles(3a-d) prepared by the reaction of o-phenylenediamines(1a-d) withα-hydroxy propionic acid 2. The synthesized compounds were characterized by their IR,~1H NMR and MS analyses.These compounds were screened for their antibacterial and antifungal activity by standard methods and found some of them active.     

Synthesis of substituted 3-(3-chloro-1H-pyrazol-5-yl)quinoxalin-2(1H)ones

Synthetic strategies to gain access to all four isomers of 3-(3-chloro-1H-pyrazol-5-yl)quinoxalin-2(1H)ones with monosubstituted benzo core (i.e., compounds 8a–d) are described. Preparation of these heterocyclic compounds succeeded starting from only two different substituted 2-nitroanilines (i.e., 3-methoxy- and 4-methoxy-2-nitroaniline) in three or five steps, respectively.     

Design,synthesis and biological evaluation of 5-(2-(4-(substituted benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues as novel anti-tubercular agents

A series of thirty-six novel 5-(2-(4-(benzo[d]isoxazol-3-yl)piperazin-1-yl)acetyl)indolin-2-one and 5-(2-(4-substitutedpiperazin-1-yl)acetyl)indolin-2-one analogues were synthesized, characterized and screened for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain. These compounds exhibited minimum inhibitory concentration between 1.56 and 50 μg/mL. Among these derivatives, compounds 10c, 10d, 10j, 10o and 10v (MIC 6.25 μg/mL) displayed moderate activity, while compounds 10e, 10l, 10q, 10w,10x, 12d, 12e and 12i (MIC 3.12 μg/mL) showed good anti-tubercular activity and compounds 10f, 10k, 10p, 10r, 12f, 12j and 12k (MIC 1.56 μg/mL) exhibited excellent anti-tubercular activity. In addition, MTT assay was accomplished on the active analogues of the series against mouse macrophage (RAW 264.7) cells to evaluate the cytotoxic effect of the newly synthesized compounds and selectivity index of the compounds was determined.     

Preparation,molecular structures,and characteristic properties of (E)-1-(2-furyl)- and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylenes and (E)-1-(3-furyl)- and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylenes

Wittig reactions of 2-furaldehyde (20) [and thiophene-2-carbaldehyde (21)] with (3-guaiazulenylmethyl)triphenylphosphonium bromide (19) in ethanol containing NaOEt at 25 °C for 24 h under argon give (E)-1-(2-furyl)-2-(3-guaiazulenyl)ethylene (22E) and (E)-1-(2-thienyl)-2-(3-guaiazulenyl)ethylene (23E) in 53 and 36% yields. Similarly, Wittig reactions of 3-furaldehyde (29) [and thiophene-3-carbaldehyde (30)] with 19 under the same reaction conditions as for 20 and 21 afford (E)-1-(3-furyl)-2-(3-guaiazulenyl)ethylene (31E) and (E)-1-(3-thienyl)-2-(3-guaiazulenyl)ethylene (32E) in 32 and 46% yields. Molecular structures and characteristic properties as well as preparation of the title E (i.e., one of the geometrical isomers) forms, with a view to comparative study, are reported. Moreover, reactions of those conjugated π-electron systems with TCNE (=tetracyanoethylene) in benzene [and in DMF (=N,N-dimethylformamide)] at 25 °C for 24 h under argon yield unique products, possessing interesting molecular structures, respectively, whose characteristic properties and crystal structures are documented, also.     

Heterocycles 35. CaL-B mediated synthesis of enantiomerically pure (R)- and (S)-ethyl 3-(2-arylthiazol-4-yl)-3-hydroxypropanoates

Herein we present the lipase catalyzed synthesis of four new enantiomerically pure (R)- and (S)-ethyl 3-(2-arylthiazol-4-yl)-3-hydroxypropanoates and their butanoates by enzymatic enantioselective acylation of the racemic alcohols rac-1a–d and by ethanolysis of the corresponding racemic esters rac-2a–d mediated by lipase B from Candida antarctica (CaL-B) in organic solvents. In terms of stereoselectivity and activity, both procedures, the acylation and alcoholysis, are successful (50% conversion, E ≫ 200). The absolute configuration of the resolution products was determined by a detailed ¹H NMR study of the Mosher’s derivatives of (S)-1a.     

Synthesis of enantiomerically pure diethyl (R)- and (S)-2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates

The synthesis and ee determination of diethyl 3-azido-2-hydroxypropylphosphonates from 2,3-epoxypropylphosphonates have been optimised. Enantiomerically enriched diethyl (R)- and (S)-2-hydroxy-3-(1,2,3-triazol-1-yl)propylphosphonates (R)-3a–j and (S)-3a–h as well as (S)-3j were synthesised from diethyl (R)- and (S)-2,3-epoxypropylphosphonates in a reaction sequence including azidolysis followed by 1,3-dipolar cycloaddition with selected alkynes.     

Microbiological transformations—XII: Microbiological reduction of racemic 1-(2',2',3'-trimethyl-cyclopent-3'-en-1'-yl)propan-2-one and 1-(2',2',3'-trimethyl-cyclopent-3'-en-1'-yl)butan-2-one by rhodotorula mucilaginosa

The microbiological reduction of (±)-l-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-one (4) and (±)-1-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-butan-2-one (5) by Rhodotorula mucilaginosa was investigated. Both enantiomers of 4 are reduced stereospecifically to corresponding alcohols; (+)-(2S, l'R)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-ol (6) and (-)-(2S,l'S)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-propan-2-ol (7). p ]The substrate selectivity in the reduction of 5 was observed: R enantiomer of 5 yields stereospecifically (+)-(2S,1'R)-(2',2',3'-trimethylcyclopent-3'-en-l'-yl)-butan-2-ol (8) while S(-)5 remains unchanged.     

Ultrasound- and microwave-assisted synthesis of (E)-1-aryl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones and (E)-1-aryl-3-[2-(pyrrolidin-1-yl)quinolin-3-yl]prop-2-en-1-ones,and their antimicrobial activity

Series of new (E)-1-aryl-3-[2-(piperidin-1-yl)quinolin-3-yl]prop-2-en-1-ones and (E)-1-aryl-3-[2-(pyrrolidin-1-yl)quinolin-3-yl]prop-2-en-1-ones have been efficiently prepared via the Claisen-Schmidt condensation of 2-(piperidin-1-yl)quinoline-3-carbaldehyde and 2-(pyrrolidin-1-yl)quinoline-3-carbaldehyde, respectively, with aryl methyl ketones under conditions of ultrasound and microwave irradiation. Structures of the products have been confirmed by IR, ¹H NMR, ¹³C NMR, and mass spectroscopy, as well as by elemental analysis. Evaluation of the in vitro antibacterial activity against bacterial (Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli) and fungal (Aspergillus niger and Candida metapsilosis) strains has revealed good antimicrobial activity of some of the tested compounds.     

Reactions of (E)-1,2-di(3-guaiazulenyl)ethylene and 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene with tetracyanoethylene (TCNE) in benzene: comparative studies on the products and their spectroscopic properties

Reactions of the title ethylene derivatives, (E)-1,2-di(3-guaiazulenyl)ethylene (1) and 2-(3-guaiazulenyl)-1,1-bis(4-methoxyphenyl)ethylene (2), with a 2 M amount of TCNE in benzene at 25 °C for 24 h under argon give new cycloaddition compounds, 1,1,2,2,11,11,12,12-octacyano-3-(3-guaiazulenyl)-8-isopropyl-5,10-dimethyl-1,2,3,6,9,10a-hexahydro-6,9-ethanobenz[a]azulene (3) from 1 and 1,1,2,2,11,11,12,12-octacyano-8-isopropyl-3,3-bis(4-methoxyphenyl)-5,10-dimethyl-1,2,3,6,9,10a-hexahydro-6,9-ethanobenz[a]-azulene (4) from 2, respectively, in 66 and 87% isolated yields. Comparative studies on the above reactions as well as the spectroscopic properties of the unique products 3 and 4, possessing interesting molecular structures, are reported and, further, a plausible reaction pathway for the formation of these products is described.     

Efficient synthesis of the cyclopentanone fragrances (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone and Magnolione

This paper describes the selective syntheses of two cis-isomer-enriched cyclopentanone fragrances: (Z)-3-(2-oxopropyl)-2-(pent-2-en-1-yl)cyclopentanone (four steps, 62% overall yield, 67% cis) and Magnolione^® (five steps, 60% overall yield, 55% cis). In addition, the asymmetric synthesis of (3aR,7aS)-5-methyl-2,3,3a,4,7,7a-hexahydro-1H-inden-1-one as well as (3a′R,7a′S)-5′-methyl-2′,3′,3a′,4′,7′,7a′-hexahydrospiro[[1,3]dioxolane-2,1′-indene] has been realized by an efficient kinetic resolution, which enables the selective synthesis of the 2S,3R-isomer-enriched 3 and 4.     

A series of 2D lanthanide (III) coordination polymers constructed from 2-(pyridin-3-yl)-1H-imidazole-4,5-dicarboxylate

Reactions of 2-(pyridine-3-yl)-1H-4,5-imidazoledicarboxylic acid (H₃PyIDC) with a series of Ln(III) ions affords ten coordination polymers, namely, {[Ln(H₂PyIDC)(HPyIDC)(H₂O)₂]·H₂O}_n [Ln=Nd (1), Sm (2), Eu (3) and Gd (4)], {[Ln(HPyIDC)(H₂O)₃]·(H₂PyIDC)·H₂O}_n [Ln=Gd (5), Tb (6), Dy (7), Ho (8) and Er (9)], and {[Y₂(HPyIDC)₂(H₂O)₅]·(bpy)·(NO₃)₂·3H₂O}_n (10) (bpy=4,4′-bipyridine). They exhibit three types of networks: complexes 1-4 are isomorphous coordination networks containing neutral 2D metal-organic layers, while complexes 5-9 are isomorphous, which consist of cationic metal-organic layers and anionic organic layers, and complex 10 is a 2D network built up from 4-connected HPyIDC²⁻ anion and 4-connected Y(III) ions. In addition, thermogravimetric analyses and solid-state luminescent properties of the selected complexes are investigated. They exhibit intense, characteristic emissions in the visible region at room temperature.     

Synthesis, structural elucidation and biological activities of organotin(IV) derivatives of (E)-3-(4-methoxyphenyl)-2-(4-chlorophenyl)-2-propenoic acid

A new series of di- and tri-organotin(IV) compounds with the general formula R_4?n SnL _n , where R?=?Me (1,2), Et (3), n-Bu (4,5), n-Oct (6), Ph (7) and L?=?(E)-3-(4-methoxyphenyl)-2-(4-chlorophenyl)-2-propenoate, were synthesized by reaction of silver salt of ligand or ligand acid with diorganotin dichloride/oxide and triorganotin chloride in 2:1 and 1:1 molar ratio, respectively. These compounds were characterized by elemental analyses, FT-IR, multinuclear (¹H, ¹³C, ¹¹⁹Sn) NMR and mass spectrometry. The spectroscopic results revealed that all the diorganotin(IV) compounds possess trigonal bipyramidal structures in solution and octahedral geometry in the solid state around the tin atom. A linear polymeric trigonal bipyramidal structure in the solid state and a tetrahedral environment around the tin atom in non-coordinating solvents has been proposed for the triorganotin(IV) compounds. All synthesized compounds were tested in vitro against a number of microorganisms to assess their biocidal activity. These studies revealed that ligand acid and some of its organotin compounds show promising activity against different strains of bacteria and fungi but lowered than reference drugs.     

Synthesis of Some 2-(3-Alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles as Novel Antibacterial Agents

Abstract

Herein, we describe a one-pot synthesis of some novel 2-(3-alkyl/aryl-5-trifluoromethylpyrazol-1-yl)-4-(coumarin-3-yl)thiazoles (6) involving the reaction of 3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazole-1-thiocarboxamides (3) with 3-bromoacetylcoumarins (5) in the presence of sodium carbonate in ethanol. Reaction of 3 with 5 in the absence of sodium carbonate, however, resulted in the formation of 2-(3-alkyl/aryl-5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-yl)-4-(coumarin-3-yl)thiazoles, which were subsequently dehydrated to 6 by refluxing in ethanol in the presence of sodium carbonate. The structure of the synthesized compounds (6) was confirmed by infrared (IR), mass, ¹H NMR, and ¹³C NMR spectra and elemental analysis data. Newly synthesized compounds (6) showed moderate to good activity against Gram-positive bacteria.     

Hypervalent triphenyl and diphenyl tin coordination compounds derived from 2-(1H-benzimidazol-2-yl)phenol

Reactions of 2-(1H-benzimidazol-2-yl)phenol (1) and SnPh₃Cl, SnPh₂Cl₂ and SnCl₄ were investigated. One tetracoordinated triphenyltin(IV) compound: triphenyltin-2-(1H-benzimidazol-2-yl)phenolate] (3) and its adducts: [O → Sn] dimethylsulfoxide triphenyltin-[2-(1H-benzimidazol-2-yl)phenolate] (4), [O → Sn] aqua triphenyltin-[2-(1H-benzimidazol-2-yl)phenolate] (5) [O → Sn] ethanol triphenyltin-[2-(1H-benzimidazol-2-yl)phenolate] (6), [N → Sn] pyridine triphenyltin-[2-(1H-benzimidazol-2-yl)phenolate] (7), where 1 acts as a monodentate ligand bound through the phenol oxygen, were obtained. In the pentacoordinated compounds 4-7, the tin atom has tbp geometry. The three phenyl groups are in equatorial positions, whereas the benzimidazole and the Lewis base are in apical positions. Two hexacoordinated tin compounds: diphenyltin-bis[2-(1H-benzimidazol-2-yl-κN)phenolate-κO] (8), dichlorotin-bis[2-(1H-benzimidazol-2-yl-κN)phenolate-κO] (9) bearing two bidentate ligands are reported. The coplanar ligands in 8 and 9 form six membered rings by oxygen and nitrogen coordination. The tin geometry is all-trans octahedral. In 8 the two phenyl groups, and in 9 the two chlorine atoms are perpendicular to the plane of the ligands. Compounds were identified in solution mainly by ¹H, ¹³C and ¹¹⁹Sn NMR and in the solid state by X-ray diffraction analysis.     

Synthesis,photophysical properties and DFT studies of 2-(3-cyano-4-((2-(4,6-dimethyl-5-nitro-1H-pyrazolo[3,4-b]pyridin-3-yl)hydrazono)methyl)-5,5-dimethylfuran-2(5H)-ylidene)malononitrile dye

The chromophore 2-(3-cyano-4-((2-(4,6-dimethyl-5-nitro-1H-pyrazolo[3,4-b]pyridin-3-yl) hydrazono)methyl)-5,5-dimethylfuran-2(5H)-ylidene)malononitrile (PPHTCF) was synthesized through coupling of diazotized 3-amino-4,6-dimethyl-5-nitropyrazolo[3,4-b]pyridine with 3-cyano-2-(dicyanomethylene)-4,5,5-trimethylfuran (TCF). The absorption solvatochromism behaviour of PPHTCF, in various solvents, presented ΔE_max = +5.40 where the positive sign suggested red shift occurrence, implying that the PPHTCF has more polar lowest excited state than its ground one. While, the PPHTCF fluorescence spectra afforded λ_em, in 575–633 nm range, and was more dependent on the solvent polarity than the absorption λ^max, despite both exhibited red shift by 58 and 42 nm, respectively. To discover the PPHTCF solvatochromism behaviour in term of “Stokes’ shift”, both of Lippert-Mataga and linear solvation-energy relationship (LSER) formulations have been utilized and the outcomes endorsed that the later was better than the former (R² = 0.9728). Finally, TD-DFT simulated absorption and emission spectra in EtOH revealed that λ^max has been resulted mainly from HOMO → LUMO; HOMO-5 → LUMO and HOMO-2 → LUMO transitions, respectively.