Synthesis and bioactivity evaluation of some novel sulfonamide derivatives

A simple and convenient method for the synthesis of biologically active sulfonamide derivatives was achieved. All the title compounds were characterized by spectral and elemental analysis. They were further screened in vitro for their abilities towards antibacterial, antifungal and antioxidant activities. The compound N,N'-(3,3′-dimethoxybiphenyl-4,4′-diyl)bis(4-fluorobenzenesulfonamide) (5b) and N-(3-(9H-carbazol-4-yloxy)-2-hydroxypropyl)-4-fluoro-N-isopropylbenzenesulfonamide (5e) exhibited good activity when compared to the standard bactericide, Chloramphenicol and fungicide, Ketoconazole respectively. The compounds (2S)-N-((2S,4S)-5-(4-Chloro-phenylsulfonamido)-4-hydroxy-1, 6-diphenylhexan-2-yl)-3-methyl-2-(2-oxotetrahydropyrim-idin-1(2H)-yl)butan-amide (4f) and (2S)-N-((2S,4S)-5-(4-fluorophenylsulfonamido)-4-hydroxy-1,6-diphenyl-hexan-2-yl)-3-methyl-2-(2-oxotetrahydropyrimidin-1(2H)-yl)bu-tana-mide (5f) exhibited good antioxidant activity when compared with standard antioxidant, Ascorbic acid.     

Antimicrobial evaluation of selected naturally occurring oxyprenylated secondary metabolites

This study tested the antimicrobial activity of eight selected naturally occurring oxyprenylated secondary metabolites against Staphylococcus aureus ATCC 29213, S. epidermidis ATCC 35984, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Results showed a moderate antimicrobial activity. The most active compounds were 3-(4-geranyloxyphenyl)-1-ethanol (4) and 3-(4-isopentenyloxyphenyl)-1-propanol (5) that were tested on mature and in-formation biofilms of all micro-organisms, moreover the cytotoxic activity was evaluated. Except for S. epidermidis, both compounds reduced significantly (p < 0.05) the microbial biofilm formation at 1/2 MIC and 1/4 MIC, in particular, compounds 4 and 5 at each concentration, inhibited E. coli biofilm formation to a greater extent, the biofilm formation was never more than 44% in respect to the control, moreover both compounds showed a low cytotoxic effect. Oxyprenylated derivatives may be of great interest for the development of novel antimicrobial therapeutic strategies and the synthesis of semi-synthetic analogues with anti-biofilm efficacy.     

Microwave Activated Solid Support Synthesis of New Antibacterial Quinolones

 A novel synthesis of 6-fluoro-7-(5-aryl-1,3,4-thiadiazol/oxadiazol-2-yl-sulfanyl)-4-quinolone-3-carboxylic acids from 7-chloro-6-fluoro-4-quinolone-3-carboxylic acid and 5-substituted 1,3,4-thiadiazoles/oxadiazoles on basic alumina under microwave activation is described. All compounds were screened for their in vitro antibacterial activity against B. lichenformis, 2689, K. aerogens 2281, S. typhimurium 2501, E. herbicola 2491, and P. vulgaris 2027 and found to possess activities comparable to that of the standard drug norfloxacin.     

Synthesis and Molecular Structure of New S‐Nucleosides of 5‐(4‐Pyridyl)‐4‐Aryl‐4H‐1,2,4‐Triazole‐3‐Thiols

The synthesis of some new S‐nucleosides of 5‐(4‐pyridyl)‐4‐aryl‐4H‐1,2,4‐triazole‐3‐thiols ( 4a‐n ) is described. Direct glycosylation of ( 4a‐n ) with tetra‐O‐acetyl‐α‐D‐glucopyranosyl bromide in the presence of potassium hydroxide followed by deacetylation using dry ammonia in methanol gave the corresponding 3‐S‐(ñ‐D‐glucopyranosyl)‐5‐(4‐pyridyl)‐4‐aryl‐4H‐1,2,4‐triazoles ( 6a‐n ) in good yields. All the compounds were fully characterized by means of ¹HNMR, ¹³C NMR spectra and elemental analyses. To assist in the interpretation of the spectroscopic data, the crystal structure of 3‐S‐(2′,3′,4′,6′‐tetra‐O‐acetyl‐β‐D‐glucopyranosyl)‐5‐(4‐pyridyl)‐4‐phenyl‐4H‐1,2,4‐triazole ( 5a ) was determined by X‐ray diffraction.     

Microwave Activated Solid Support Synthesis of New Antibacterial Quinolones

Summary.  A novel synthesis of 6-fluoro-7-(5-aryl-1,3,4-thiadiazol/oxadiazol-2-yl-sulfanyl)-4-quinolone-3-carboxylic acids from 7-chloro-6-fluoro-4-quinolone-3-carboxylic acid and 5-substituted 1,3,4-thiadiazoles/oxadiazoles on basic alumina under microwave activation is described. All compounds were screened for their in vitro antibacterial activity against B. lichenformis, 2689, K. aerogens 2281, S. typhimurium 2501, E. herbicola 2491, and P. vulgaris 2027 and found to possess activities comparable to that of the standard drug norfloxacin. Received May 2, 2000. Accepted (revised) June 13, 2000     

Benzimidazole condensed ring systems. 2. New synthesis of substituted 1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitriles and related derivatives

The synthesis of some 3-substituted and 2,3-disubstituted-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbo-nitriles 5,6 by fusing 1H-benzimidazole-2-acetonitrile 1 with some β-keto esters 2,4 in the presence of ammonium acetate or with ethyl β-aminocrotonate 3 is described. The tricyclic compounds were converted to their N-5 methyl of N-5 ethyl derivatives 8,9. Vilsmeir-Haack formylation of 3-methyl-1-oxo-1H,5H-pyrido[1,2-a]-benzimidazole-4-carbonitrile 5a afforded its 2-formyl derivative 10. Chlorination of 5 and 6 with phosphorus oxychloride yielded the respective 1-chloropyrido[1,2-a]benzimidazole-4-carbonitriles 11,12 which were utilized to prepare the 1-azido, 1-amino, 1-piperidino and 1-methoxy derivatives of the ring system. Compound 11a exhibited strong in vitro activity against S. aureus. Four compounds were screened against P-388 lymphocytic leukemia in mice but were inactive.     

Efficient access to some new pyrimidine derivatives and their antimicrobial evaluation

1-[4-(3-Hydroxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl]ethanone ( 1 ) was used as a precursor for heterocyclic synthesis. Condensation of compound 1 with monochloroacetic acid and benzaldehyde gave thiazolopyrimidine 2 which in turn underwent cyclization with malononitrile dimmer to afford malononitrile derivative 3 . Also, the reaction of compound 1 with benzaldehyde under a basic condition produced chalcone 4 . Chalcone 4 can be used as a key intermediate for further preparation of heterocyclic compounds. In addition, compound 1 was allowed to react with malononitrile dimmer and/or ethyl chloroacetate to give pyrimidines 8 and 9 , respectively. Alkylation of compound 8 with ethyl chloroacetate afforded S-alkylated product 10 which was treated with hydrazine hydrate to yield the hydrazino derivative 11 . Alternative synthesis of compound 10 was taken place through reaction of compound 9 with malononitrile dimmer. The biological activity of the synthesized compounds was investigated. Compounds 1 , 4 , 5 , and 8 recorded high activities against Gram positive bacteria (S. aureus). Structures of the new synthesized compounds were elucidated by elemental analysis and spectral data.     

DABCO mediated one pot synthesis of 2-(3-benzyl-2, 6-dioxo-3, 6-dihydropyrimidin-1[2H]-yl)-N-(4-(1, 3-dioxo-1H-benzo [de]isoquinolin-2[3H]-yl) aryl) acetamides as antimicrobial agents

We report herein DABCO mediated one pot synthesis of 2-(3-benzyl-2, 6-dioxo-3,6-dihydropyrimidin-1[2H]-yl)-N-(4-(1,3-dioxo-1H-benzo[de]isoquinolin-2[3H]-yl) aryl) acetamides ( 4a-j ). The silent features of this new one pot synthesis include the shorter reaction time, high yields, simple workup, and simultaneous formation of N-Amide and N-benzyl bonds in the one pot. The newly synthesized compounds ( 4a-j ) were characterized by different spectral techniques such as IR, ¹H-NMR, ¹³C-NMR, HRMS. All the synthesized compounds were evaluated for their anti-bacterial and anti-fungal activities. The anti-bacterial activities results reveal that the compounds 4a , 4g , 4i , and 4j are most active against S. aureus. In the case of B. subtilis the compounds 4a , 4i , and 4j are found to be most active. The compounds 4c , 4e , 4i , and 4j are most active against E. coli. In the case of P. aeruginosa 4a , 4i & 4j are found to be more active. On the other hand, the anti-fungal activity result shows that the compounds 4d , 4f , 4i , and 4j are more active against A. niger. The compounds 4a , 4d , 4i , and 4j are found to be more active against C. albicans.     

Synthesis of 3-amino-5H-pyrimido[5,4-b]indol-4-one derivatives

Starting with ethyl 3-aminoindole-2-carboxylate, the synthesis of 3-amino-5H-pyrimido[5,4-b]indole-2,4-dione 5 , 3-amino-5H-pyrimido[5,4-b]indol-4-one 10 and some related compounds is described. Preliminary results about the inhibition of platelet aggregation by these compounds is reported.     

Synthesis and Antimicrobial Studies of New Spiropyran Quinazolinone Derivatives with Amide,Urea, and Sulfonamide Moieties

Three new series of quinazolinone derivatives containing amide, urea, and sulfonamide were synthesized through multistep synthesis. The required intermediates 4‐[(4′‐oxo‐2,3,3′,4′,5,6‐hexahydro‐1′H ‐spiro[pyran‐4,2′‐quinazolin]‐1′‐yl)methyl]benzoic acid 4 and 1′‐(3‐aminobenzyl)‐2,3,5,6‐tetrahydro‐1′H ‐spiro[pyran‐4,2′‐quinazolin]‐4′(3′H )‐one 8 were prepared by hydrolysis of ester and reduction of nitro intermediates. Three different series of compounds were synthesized from these two scaffolds. The key scaffolds 4 and 8 were successfully converted to target molecules via amides 5a – k , urea 9a – f , and substituted sulfonamides 10a – e . The chemical structures of newly synthesized compounds were characterized by spectral analysis. The structure of 5d was confirmed by X‐ray crystallography study. These newly synthesized compounds were screened for antibacterial studies against Staphylococcus epidermidis , Salmonella typhi , Proteus mirabilis , and Shigella sonnei and for the antifungal activity against Aspergillus niger and Candida albicans . Among all the compounds, 9b – d showed excellent activities against S. typhi . Compound 9a showed moderate activity against all fungi stains, and 5I showed moderate activity against P. mirabilis , while the other derivatives showed fairly good activities.     

Benzimidazole condensed ring systems. 1. Syntheses and biological investigations of some substituted pyrido[1,2-a]benzimidazoles

The synthesis of some substituted 3-hydroxy-1-oxo-1H,5H-pyrido[1,2-a]benzimidazole-4-carbonitriles and 4-ethyl carboxylates 3 and their 0- and N-dialkyl derivatives 5,6 is described. 3-Ethoxy-5-ethyl-2-phenyl-1H,5H-pyrido[1,2-a]benzimidazol-1-one 7 was obtained during the course of ethylating the parent ester 3t with triethyl phosphate. Chlorination of 3 with phosphorus oxychloride afforded the corresponding 1,3-dichloropyrido[1,2-a]benzimidazoles 8 which were converted to a variety of azido, amino, morpholino and methoxy derivatives of the system. The synthesis of the indolopyridobenzimidazole 15 is also described. Two compounds exhibited in vitro antibacterial activity. Many compounds were screened for antileukemic, antimicrobial, herbicidal and plant antifungal potencies but were inactive.     

Microwave‐Assisted Synthesis of Novel Spiro Phosphonyl Thiazolo Pyrazole Glycosides as Potential Nematicidal Agents

A series of novel dimethyl 7‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐4‐(4‐fluorophenyl)‐9‐oxo‐8‐phenyl‐6‐thia‐1,2,8‐triazaspiro[4.4]non‐2‐en‐3‐ylphosphonate 2a – g were synthesized by the reaction of chalcone derivatives of 2‐((3aR,5S,6S,6aR)‐6‐((1‐(4‐chlorophenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)‐2,2‐dimethyltetrahydrofuro[2,3‐d][1,3]dioxol‐5‐yl)‐3‐phenylthiazolidin‐4‐one 1 with Bestmann–Ohira reagent. The chemical structures of newly synthesized compounds were elucidated by IR, NMR, MS, and elemental analysis. The compounds 2a – g were evaluated for their nematicidal activity against Dietylenchus myceliophagus and Caenorhabditis elegans; compounds 2b , 2c , 2g , and 2f showed appreciable nematicidal activity.     

Phosphonium Ylides Stabilized with Cyano Group and 5-Acylamino-4-phenyl-2-thiazolyl Residue

Available ylide reagent Ph₃P = C(CN)C(S)NH₂ readily enters cyclocondensation with N-(chlorophenacyl)benzamide and its analogs. By this route were prepared new stabilized phosphonium ylides containing cyano group and the corresponding 5-acylamino-4-phenyl-2-thiazolyl fragment. All these compounds even under standard conditions are dephosphorylated under the action of hydrogen chloride in acetic acid to form 5-acylamino-4-phenyl-2-cyanomethylthiazoles in high yields. Their structure was proved by spectroscopic studies and independent synthesis.     

NEW AND CONVENIENT SYNTHESIS OF (R) AND (S) OF 2-METHYL-3-OXA-5-(TERT-BUTYLDIPHENYLSILYLOXYL) METHYLPENTANOATE AND 2-METHYL-3-OXA-5- (TERT-BUTYLDIMETHYLSILYLOXYL)METHYLPENTANOATE

Abstract

(R) and (S) of 2-Methy1-3-oxa-5-(tert-butyldiphenylsilyloxyl)methy1pentanoate (4a. 6a) and (R) and (S) of 2-methy1-3-oxa-5-(tert-butyldimethylsilyloxyl)methylpentanoate (4b, 6b) were synthesized by the reaction of the preparative compounds (2a, 2b) with (R) and (S) methy1lactate (3, 4) in the presence of a silver (1) oxide catalyst (Method B). The title compounds are useful for the synthesis of different natural products such as epothilones.     

Synthesis of nanosized materials for lithium-ion batteries by mechanical activation. Studies of their structure and properties

This short review reports on the synthesis of nanosized electrode materials for lithium-ion batteries by mechanical activation (MA) and studies of their properties. Different structural types of compounds were considered, namely, compounds with a layered (LiNi_{1 − x − y} Co _x Mn _y O₂), spinel (LiMn₂O₄, Li₄Ti₅O₁₂), and framework (LiFePO₄, LiTi₂(PO₄)₃) structures. The compounds also differed in electronegativity, which varied from 10⁻⁴ S cm⁻¹ for LiCoO₂ to 10⁻⁹ S cm⁻¹ for LiFePO₄. The preliminary MA of mixtures of reagents in energy intensive mechanoactivators led to the formation of highly reactive precursors, and annealing of the latter formed nanosized products (the mean particle size is 50–200 nm). The local structure of the synthesized compounds and the composition of their surface were studied by spectral methods. An increase in the dispersity and defect concentration, especially in the region of the surface, improved some electrochemical characteristics. It increased the stability during cycling (LiMn₂O₄, at 3 V) and the regions of the formation of solid solutions during cycling (Li₄Ti₅O₁₂, LiFePO₄), led to growth of surface Li-ion conductivity (LiTi₂(PO₄)₃), etc. The mechanochemical approach was also used for the synthesis of core-shell type composite materials (LiFePO₄/C, LiCoO₂/MeO _x ) and materials based on two active electrode components (LiCoO₂/LiMn₂O₄).     

Homochiral Dysprosium Phosphonate Nanowires: Morphology Control and Magnetic Dynamics

Controllable synthesis of uniformly distributed nanowires of coordination polymers with inherent physical functions is highly desirable but challenging. In particular, the combination of chirality and magnetism into nanowires has potential applications in multifunctional materials and spintronic devices. Herein, we report four pairs of enantiopure coordination polymers with formulae S-, R-Dy(cyampH)₃ ⋅ CH₃COOH ⋅ 2H₂O ( S -1 , R -1 ), S-, R-Dy(cyampH)₃ ⋅ 3H₂O ( S -2 , R -2 ), S-, R-Dy(cyampH)₂(C₂H₅COO) ⋅ 3H₂O ( S -3 , R -3 ) and S-, R-Dy(cyampH)₃ ⋅ 0.5C₂H₅COOH ⋅ 2H₂O ( S -4 , R -4 ) [cyampH₂=S-, R-(1-cyclohexylethyl)aminomethylphosphonic acids], which were obtained depending on the pH of the reaction mixtures and the specific carboxylic acid used as pH regulator. Interestingly, compounds 3 were obtained as superlong nanowires, showing 1D neutral chain structure which contains both phosphonate and propionate anion ligands. While compounds 1 , 2 and 4 appeared as block-like crystals, superhelices and nanorods, respectively, and exhibited similar neutral chain structures containing only phosphonate ligand. Slow magnetization relaxation characteristic of single-molecule magnet (SMM) behavior was observed for compounds S -1 and S -3 . Theoretical calculations were performed to rationalize the magneto-structural relationships.     

(−)‐(3S)‐3‐(Tosylamino)butano‐4‐lactone,a Versatile Chiral Synthon for the Enantioselective Synthesis of Different Types of Polyamine Macrocycles: Determination of the Absolute Configuration of (−)‐(R)‐Budmunchiamine A

(−)‐(3S)‐3‐(Tosylamino)butano‐4‐lactone ( 1 ) and its derivative ethyl (−)‐(3S)‐4‐iodo‐3‐(tosylamino)butanoate ( 2 ) are presented as easily accessible chiral building blocks for the construction of a range of different macrolactam frameworks important for the synthesis of naturally occurring polyamine alkaloids as well as for establishing a substance library of such compounds, including S‐containing derivatives for biological tests. In addition to that, the absolute configuration of the spermine alkaloid (−)‐(R)‐budmunchiamine A ( 3 ) from Albizia amara was determined by total synthesis according to the new methodology.     

‘Click Synthesis’ of Some Novel Benzimidazol Oxime Ethers Containing Heterocycle Residues as Potential ß‐Adrenergic Blocking Agents

The ‘click synthesis’ of some novel O‐substituted oximes, 5a – 5j , which contain heterocycle residues, as new analogs of ß‐adrenoceptor antagonists is described (Scheme 1). The synthesis of these compounds was achieved in four steps. The formation of (E)‐2‐(1H‐benzo[d]imidazol‐1‐yl)‐1‐phenylethanone oxime, followed by their reaction with 2‐(chloromethyl)oxirane, afforded mixture of oil compounds 3 and 4 , which by a subsequent tetra‐n‐butylammonium bromide (TBAB)‐catalyzed reaction with N H heterocycle compounds (Scheme 1), led to the target compounds 5a – 5j in good yields.     

The One Step Synthesis of 2-(2-Bromo-5- methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]- 1,2,4-triazol-6-(5H)-ones and the Evaluation of the Anticonvulsant Activity

A smooth one-step synthesis of 2-(2-bromo-5-methoxyphenyl)-5-(3-arylidene)-1,3-thiazolo[3,2-b]-1,2,4-triazol-6-(5H)-ones (4a–n) is described. The newly prepared compounds are characterized by analytical and IR, ¹ H NMR, ¹³ C NMR, and FABMS spectral analysis. A few compounds are screened for anticonvulsant activity. Compounds 4i and 4n exhibit promising anticonvulsant activity and are recommended for further studies.     

Novel sulfur-nitrogen-fluorine compounds : synthesis and properties of SF5NHF,SF5NClF and SF4NF

Using reactions developed for the synthesis of CF₂NF, CF₃NClF and CF₃NHF from ClCN, F₃SN can now be converted in high yield to the analogous sulfur compounds, SF₄NF, SF₅NClF and SF₅NHF. N-fluorotetrafluorosulfurimine is the simplest sulfur(VI) imine and is a rigid molecule. Details on the synthesis and properties of these novel compounds will be presented.