Yakdhane Kacem

Synthesis and pharmacological profile of 6-methyl-3-isopropyl-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide derivatives: non-steroidal anti-inflammatory agents with reduced ulcerogenic effects in the rat.

The new anti-inflammatory agents 6-methyl-3-isopropyl-2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide 6a and its analogues 6b-f were synthesized from L-valine. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 6a-f (5-20 mg/kg, i.p.) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay in albino rats, and their effects are comparable to that of piroxicam (5 mg/kg, i.p.), used as a reference drug. The nature of the substituents on the sulfonamide nitrogen and those on position three had a pronounced effect on the anti-inflammatory activity. Studies of structure-activity relationships have led to selection of compound 2,6-dimethyl-3-isopropyl-1,2-benzothiazin-3,4-diol 1,1-dioxide 6 f which exhibited the most potent activity (61.7% inhibition at 5 mg/kg, i.p. and ED(50)=4.5 mg/kg, i.p.). Comparison of the gastrointestinal safety of compounds 6a-f with that of piroxicam showed a far better tolerability for our products. This comparison was based on the ulcer index and the pH of gastric content.

New chitosan microspheres supported [bis(2-methylallyl)(1,5-cyclooctadienne)ruthenium(II)] as efficient catalysts for colour degradation in the presence of hydrogen peroxide

This paper concerns the immobilisation of either [bis(2-methylallyl)(1,5-cyclooctadienne)ruthenium(II)] (I) or ruthenium chloride (RuCl3) (II) on chitosan microspheres (catalyst I and catalyst II, respectively). These heterogenised catalysts were used for the oxidative degradation of two acid dyes, i.e. [Calmagite (Calma) and Acid Blue 25 (AB25)] in aqueous solution at pH 7.0 in the presence of hydrogen peroxide (H2O2). Prepared solid supports were characterised by Fourier transform infrared (FTIR) spectral study, thermogravimetry (TG), differential thermogravimetry (DTG) and differential scanning calorimetry (DSC) analyses. The efficiency of decolourisation was justified using UV–visible spectroscopic analysis. The factors affecting dye degradation were studied. Some tests for Calma decolourisation achieved up to 100% colour removal using catalyst I. The pseudo first-order equation was shown to fit degradation kinetics in most cases. However, for some cases, it was necessary to use a reversible equation. The energetic parameters were determined and the activation energy (E a) was found to be low, between 11 and 36 kJ mol−1, confirming that these catalysts were very efficient for the degradation of anionic dyes using H2O2. The interpretation of the equilibrium sorption data complies well with the Freundlich adsorption model. The combination of adsorption process and catalytic oxidation made the new developed catalyst systems to achieve a simple and efficient water treatment.

Synthesis of new 3-substituted-2H-1,2-naphthothiazin-4(3H)-one 1,1-dioxides via directed ortho-metalation reaction

Abstract The reaction of compounds 6a – i , readily available from α-amino acids, with an excess of lithium diisopropylamide, leads to new 3-substituted-2 H -1,2-naphthothiazin-4(3 H )-one 1,1-dioxides 7a – i , with yields ranging between 21 and 70%. The key steps are: the naphthylsulfonyl ortho-deprotonation based on the directed ortho-metalation reaction followed by a regiospecific intramolecular cyclisation reaction. Lithiation–deuteration experiments carried out on the naphthylsulfonamides 8 and 9 using n -BuLi and LDA demonstrated the regioselectivity of the deprotonation of the H-3 over the H-1 one of the naphthalene ring.

New N-Substituted (E)-4-Arylidene Isoquinoline-1,3-dione Derivatives: NMR Spectroscopic Investigation and Antibacterial Activity

Abstract New N-substituted 4-arylidene-isoquinoline-1,3-dione derivatives were obtained as one geometrical isomer by aldol condensation of the appropriate aldehyde and the corresponding N-substituted homophthalimides. The structural elucidation of compounds 3a–h was established by infrared and NMR spectroscopy including 1 H, 13 C, CH CORR, and distortionless enhancement by polarization transfer measurements. Compounds 3d–h were evaluated for their antibacterial activity against some strains of bacteria using the disc diffusion method and microdilution tests. GRAPHICAL ABSTRACT

1,3-Dipolar Cycloaddition of Nitrones with 5-Methylenehydantoins: Synthesis and Transformation of New Spirohydantoin Derivatives

1,3-Dipolar cycloaddition of various acyclic nitrones with 5-methylenehydantoin derivatives afforded new chiral spiroadducts in good yields. All the spirohydantoins were obtained through a regio- and stereospecific pathway, and the spirocarbon atom was linked to the isoxazolidine oxygen atom. A representative example of the reduction of the spirohydantoin 8 with Zn/AcOH led to the substituted 1,3-aminoalcohol hydantoin 20.

New palladium–oxazoline complexes: Synthesis and evaluation of the optical properties and the catalytic power during the oxidation of textile dyes

Summary The present paper describes the synthesis of new palladium–oxazoline complexes in one step with good to high yields (68–95%). The oxazolines were prepared from enantiomerically pure α-aminoalcohols. The structures of the synthesized palladium complexes were confirmed by NMR, FTIR, TOFMS, UV–visible spectroscopic analysis and X–ray diffraction. The optical properties of the complexes were evaluated by the determination of the gap energy values (E g) ranging between 2.34 and 3.21 eV. Their catalytic activities were tested for the degradation of Eriochrome Blue Black B (a model of azo dyes) in the presence of an ecological oxidant (H2O2). The efficiency of the decolorization has been confirmed via UV–visible spectroscopic analysis and the factors affecting the degradation phenomenon have been studied. The removal of the Eriochrome reached high yields. We have found that the complex 9 promoted 84% of color elimination within 5 min (C 0 = 30 mg/L, T = 22 °C, pH 7, H2O2 = 0.5 mL) and the energetic parameters have been also determined.

New chiral 4-substituted 2-cyanoethyl-oxazolines: synthesis and assessment of some biological activities.

This paper describes the synthesis of new enantiomerically pure 2-cyanoethyl-oxazolines in one step starting from a wide range of amino alcohols and 4-ethoxy-4-iminobutanenitrile with high to good yields (73-96%) via an appropriate procedure which can be used for a selective synthesis of mono-oxazolines. A simple operation as well as a practical separation is additional eco-friendly attributes of this method. All the synthesized compounds were identified and characterized with their physicochemical features and their spectral data ((1)H NMR, (13)C NMR and TOFMS ES(+)). Among the prepared mono-oxazolines, the mono-oxazoline (3a) [3-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile] was tested to detect some biological activities. This compound was studied in vitro given the various types of pharmacological properties characterizing these compounds such as antioxidant, antimicrobial and analgesic activities. The antioxidant activity and mechanism of (3a) were identified using various in vitro antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and superoxide anion radicals (O2(-)) scavenging activity. In addition, compared to Quercetin, the tested synthetic product reveals a relatively-strong antiradical activity towards the DPPH (activity percentage of 81.22%) free radicals and significantly decreased the reactive oxygen species such as (O2(-)) formation evaluated by the non-enzymatic (nitroblue tetrazolium/riboflavine) and the enzymatic (xanthine/xanthine oxidase) systems. Related activity values were, respectively, 66% and 60.30%. The oxazoline (3a) showed a high ability to reduce the O2(-) generation and proved to be a very potent radical scavenger. On the other hand, the analgesic property of the 3[(4S)-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile (3a) was demonstrated. The subcutaneous administration of (3a) produced a significant reduction in the number of abdominal constrictions amounting to 73.81% in the acetic acid writhing test in mice. In addition to these advances, the oxazoline (3a) has been investigated as an antimicrobial agent. Our results showed that this molecule exhibited various levels of antibacterial effect against all the tested bacterial strains.

REGIOSELECTIVE SYNTHESIS AND STRUCTURE OF NEW SPIRO-ISOQUINOLINEDIONE DERIVATIVES

New spiro-isoquinolinoisoxazolines were prepared by regioselective 1,3-dipolar cycloaddition of 4-arylidene-isoquinoline-1,3-dione derivatives la-d with arylnitrile oxides 2e-g. In all cases, two regioisomers 3ae-dg and 4ae-dg were isolated with comparable ratios. Regioselectivity was established by unambiguous structural NMR assignments and X-ray diffraction analysis.

Enantiopure Schiff bases of amino acid phenylhydrazides: impact of the hydrazide function on their structures and properties

A rapid and eco-friendly synthesis of new enantiopure Schiff bases 5a–e was performed from various α-amino acid phenylhydrazides and 2-hydroxynaphthaldehyde using microwave or ultrasound irradiation in yields ranging from 57 to 75%. These imines were characterized using 1H & 13C NMR, FTIR, mass and UV-vis spectroscopies. In addition, the solid state molecular structure of 5b was determined by single crystal X-ray diffraction which shows that this compound adopts the zwitterionic form, crystallizing in the non-centrosymmetric orthorhombic system with the space group P212121. DFT calculations show that the BMK/6-31G(2df,2pd) method in the gas phase is well adapted to describe the geometry of the solid state. Theoretical results corroborate the ionic character of this species in concordance with spectroscopic results and lead to a new thin description. The Schiff bases 5a–e behave as organic semiconductors with Eog ≈ 2.77 eV. The in vitro antibacterial study showed that these molecules exhibited various levels of antibacterial effect against all of the tested bacterial strains.

Synthesis and antibacterial activity of new spiro-isoquinolin-1-ones

New spiro-isoquinolinones have been efficiently synthesised by the condensation of secondary N-allylamines and 2-bromobenzoyl chloride, followed by a sequential procedure involving an intramolecular Heck reaction and 1,3-dipolar cycloaddition. The regiospecificity of the reaction was established by mono and two-dimensional NMR analysis. The spiro-compounds were evaluated for their antibacterial activity against some strains of bacteria using the disc diffusion method and micro-dilution tests.