Mechanistic study on the oxidation of l-phenylalanine by copper(III) in aqueous alkaline medium: a kinetic approach

Abstract  

Oxidation of the amino acid l-phenylalanine by diperiodatocuprate(III) in alkaline medium at constant ionic strength of 0.25 mol dm⁻³ was studied spectrophotometrically at different temperatures (298–313 K). The reaction between diperiodatocuprate(III) and l-phenylalanine in alkaline medium exhibits 1:2 stoichiometry. Intervention of free radicals was observed in the reaction. Based on the observed orders and experimental evidence, a mechanism involving monoperiodatocuprate(III) as the reactive oxidant species has been proposed, proceeding through the formation of a complex and reaction of the intermediate of l-phenylalanine with monoperiodatocuprate(III) to give the products. The products were identified by spot test, infrared (IR), and gas chromatography-mass spectrometry (GC-MS). The reaction constants involved in the different steps of the mechanism were calculated. The activation parameters with respect to the slow step of the mechanism were computed and are discussed. The thermodynamic quantities were determined for different equilibrium steps. The isokinetic temperature was also calculated and found to be 331 K.     

Selection of protecting groups and synthesis of a β-1,4-GlcNAc-β-1,4-GlcN unit

Abstract  

The synthesis of the disaccharide tert-butyldimethylsilyl (4-O-acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside, designed as a repeating unit appearing in oligo- and polysaccharides, which exhibits a distinguished “obverse–reverse” property in β-1,4-glucan chain, was accomplished. This disaccharide was synthesized by glycosylation of a phthalimido sugar with an azido sugar. A selective removal of the two different protecting groups at C-2 for obtaining 2-acetamido-4-O-(2-amino-2-deoxy-β-d-glucopyranosyl)-2-deoxy-β-d-glucopyranose indicates that the selection and combination, using phthalimido and azido as protecting groups, are an excellent strategy for synthesizing such target disaccharides.     

A novel polycondensation method for the synthesis of a two-faced β-1,4-glucan

Abstract  

The stereospecific synthesis of a chitosan derivative repeating 2-azido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl-(1 → 4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-d-glucopyranose, which has two distinguishing faces, was achieved by polycondensation of the sole starting disaccharide, trichloroacetimidoyl 2-azido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl-(1 → 4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-d-glucopyranoside in a short and efficient way.     

Equilibrium studies on complex formation reactions of dichlorido[(R,R)-trans-1,2-diaminocyclohexane]platinum(II) complex with ligands of biological significance

Abstract  

The hydrolysis and complex formation equilibria of [Pt(dach)(H₂O)₂]²⁺, where dach is (R,R)-trans-1,2-diaminocyclohexane, with some sulfur- and nitrogen-bonding ligands, such as l-methionine, glutathione, inosine, inosine-5′-monophosphate, and guanosine-5′-monophosphate, were studied in aqueous 0.10 M NaClO₄ solution at 298 K by potentiometric titrations. The experimentally determined pK _a values for the studied diaqua complex were 6.00 and 10.03, respectively. The acid dissociation constants of the ligands were also determined. The stoichiometry and stability constants of the formed complexes are reported, as well as the concentration distribution of the various complex species evaluated as a function of pH. In all studied systems, species with one coordinated molecule of ligand were detected. However, only in systems with l-methionine and inosine, complexes with two molecules of ligand directly coordinated to the Pt(II) ion were found. The results also show that glutathione formed the most stable complexes. These results could contribute to better understanding of the interactions between Pt(II) complexes and biologically significant molecules.     

Synthesis of a chito-tetrasaccharide β-1,4-GlcNAc-β-1,4-GlcN repeating unit

Abstract  

tert-Butyldimethylsilyl (4-O-acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside (Kawada and Yoneda [MOCHEM-D-09-00120], 2009), designed as a repeating disaccharide unit in a β-glucan having two different faces, was converted into a glycosyl donor and an acceptor. The glycosyl acceptor was glycosylated with the donor to afford a chito-tetrasaccharide derivative in good yield. Phthalimido and azido groups in the tetrasaccharide were successively converted into acetamido and free amino groups, and all other protecting groups were cleaved to obtain the chito-tetrasaccharide (2-amino-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-(2-amino-2-deoxy-β-d-glucopyranosyl)-(1 → 4)-2-acetamido-2-deoxy-d-glucopyranose.     

Toward the synthesis and biological evaluation of hirsutide

Abstract  

The present investigation deals with the synthesis of a N-methylated cyclotetrapeptide, hirsutide (2), by coupling of the dipeptide units Boc-l-phenylalanyl-l-N-methylphenylalanine-OH and l-valyl-l-N-methylphenylalanine-OMe followed by cyclization of the linear tetrapeptide fragment. The chemical structure was established on the basis of analytical as well as spectroscopic data. The newly synthesized cyclic peptide was subjected to pharmacological screening and found to be highly potent against the gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae at 6 μg cm⁻³. In addition, potent antihelmintic activity against the earthworms Megascoplex konkanensis and Pontoscotex corethruses at 1 and 2 mg cm⁻³, and potent cytotoxic activity against Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma cell lines with IC₅₀ values of 14 and 22 μM were also observed. Studies revealed that the pentafluorophenyl ester method employing a catalytic amount of N-methylmorpholine proved to be better for cyclization of the linear tetrapeptide unit.     

Chiral separation of ofloxacin enantiomers by ligand exchange chromatography

Abstract  

The enantioseparation conditions of ligand exchange chromatography were examined using ofloxacin enantiomers. A C₁₈ column was used with the mobile phase consisting of a methanol–water solution (containing different concentrations of l-isoleucine and copper sulfate) at flow rate of 0.5 cm³ min⁻¹. The effect of different kinds and concentrations of ligands, bivalent ligand ions, and organic modifier, and temperature on enantioseparation were evaluated; the results showed that enantioselectivity was strongly affected by the ligand concentration of the mobile phase. Under the optimum conditions (methanol/water 20:80 v/v, containing 2.5 mmol dm⁻³ l-isoleucine and 0.6 mmol dm⁻³ Cu²⁺, room temperature), baseline separation of the two enantiomers was obtained with resolution of 1.32 in less than 30 min. The separation method was used to analyze the ofloxacin enantiomers in different commercial medicines.     

Imatinib mesylate cocrystals: synthesis, screening, and preliminary characterization

Abstract  

Drug–drug cocrystals of imatinib mesylate with several cocrystal formers, i.e. 5-chlorouracil, 5-fluorouracil, hydroxyurea, 5-fluorocytosine, N-acetylcytosine, chlorogenic acid, dacarbazine, curcumin, creatine, orotic acid, l-cysteine, glutathione, and caffeic acid, were prepared from mixtures by cogrinding or solvent cocrystallization. The samples prepared were analyzed by FTIR, DSC, and XRPD. Formation of cocrystals with different stoichiometry was observed. Novel cocrystals of imatinib mesylate with 5-fluorouracil or hydroxyurea were identified, characterized, and selected by the solid form screening approach. These cocrystals were non-hygroscopic and chemically and physically stable to thermal stress under the testing conditions.     

Electrochemical study of gallium(III) with <Emphasis Type="SmallCaps">l</Emphasis>-glutamine at the dropping mercury electrode

Abstract  

Gallium complexes of l-glutamine have been studied polarographically in aqueous media. The reduction was found to be irreversible and diffusion controlled in the presence of 0.1 M KNO₃ and 0.002% Triton-x-100. The values of kinetic parameters, transfer coefficient (α _n), and formal rate constant ( k_{\textf,\texth}⁰ k_{{{\text{f}},{\text{h}}}}^{0} ) of the electrode reactions were calculated by Koutecky's method. The stability constants and composition of the gallium(III)-l-glutamine complexes were evaluated with the help of the Deford-Hume method. The values of stability constants of 1:1, 1:2, and 1:3 gallium(III)-l-glutamine complexes are 1.35, 6.5, and 1,350 at 30 °C, respectively. The values of thermodynamic parameters, the free energy of activation, the enthalpy of activation, and the entropy of activation have been determined at 30 °C. The formation of the metal complexes has been found to be non-spontaneous, endothermic in nature, and entropically favorable at higher temperature.     

Modular access to heterocycles: methyl 3-aminobenzo[b]thiophene-2-carboxylate–thiourea linkage or pyrimidine-4-one-2-thione formation

Abstract  

Modular conditions for the formation of thioureas or pyrimidine-4-one-2-thiones connected to the benzo[b]thiophene, benzene and indole structures were performed. A benzo[b]thiophene isothiocyanate derivative was used as a model to study the condensation with simple aromatic amines and amino-l-sorbose derivative. The construction of pyrimidine-4-one-2-thiones using basic conditions afforded efficiently new heterocyclic aromatics, which were further transformed using the alkylated sulfur as a leaving group in palladium-catalyzed cross-coupling reactions.     

Determination of dissociation kinetics of 188Re(I)-pharmaceuticals by free-ion selective radiotracer extraction

Due to physical decay properties commonly associated with therapeutic radionuclides, ¹⁸⁸Re (t _1/2 = 16.98 h, E _max = 2.12 MeV) is of high interest for endovascular brachytherapy and endoradiotherapy in general. Rhenium precursors in the low oxidation state +I, such as the organometallic fac-[Re(H₂O)₃(CO)₃]⁺ are promising lead compounds compared to those with oxidation states +III and +V since they can be prepared under mild conditions and do not tend to reoxidize to oxidation state +VII while multidentate ligands can be attached under substitution of coordinated water molecules. This study comprises the application of the Free-Ion Selective Radiotracer Extraction (FISRE) technique in order to determine dissociation rate constants of complexes bearing the [¹⁸⁸Re(CO)₃]⁺-core at tracer levels in vitro with regards to their time-dependent kinetic speciation. As ligands, the tridentate l-histidine as well as the dipeptides l-carnosine (β-alanyl-l-histidine) and glycyl-l-histidine were chosen in order to study the effects of different moieties attached to the primary amine of l-histidine.     

Olefin epoxidation with H2O2 in the presence of Mn(II) dicarboxylate coordination polymer catalysts

Abstract  

The Mn(II) dicarboxylate coordination polymers [Mn(μ-terephthalate)(H₂O)₂] _n , [Mn(μ-oxalate)(H₂O)₂] _n , and [Mn(μ-d-(−)-tartrate)] _n were prepared in water and characterized by FT-IR spectroscopy and CHN analysis. Particles of the terephthalate catalyst were also synthesized, by reaction of terephthalic acid and MnCl₂·4H₂O by a sonochemical method. The catalytic potential of these coordination polymers as slow-release sources of catalytically active Mn species was tested in the oxidation of cyclooctene to its epoxide in acetonitrile, using hydrogen peroxide as oxygen source. For the terephthalate species the catalytic activity was found to increase with increasing dielectric constant and dipole moment of the solvent (being highest in acetonitrile), with reaction temperature to a maximum at 60 °C, and with an imidazole co-catalyst (highest activity found for a imidazole-to-catalyst molar ratio of 20:1). Good activity with more than 64% conversion in 24 h was obtained for epoxidation of cyclooctene and cyclohexene, whereas low yields only were obtained from aryl-substituted olefins. Some exo versus endo regioselectivity was found for norbornene.     

Synthesis of pseudo-C-nucleosides from β-formyl-α,β-unsaturated ester bearing a β-furanosidic moiety

Abstract  

Pseudo-C-nucleosides have potential biological activity, and an efficient synthesis of new pseudo-C-nucleosides has been developed via the reaction of a β-formyl-α,β-unsaturated ester bearing a β-sugar moiety with hydrazines in neutral and acidic conditions. The preparation of the β-formyl-α,β-unsaturated ester was accomplished by oxidation of the secondary hydroxyl group of 3-O-benzyl-1,2-O-isopropylidene-α-d-glucofuranose, followed by elongation of its carbon chain with (ethoxycarbonylmethylene)triphenylphosphorane and oxidation of the hydroxymethyl group.     

Anticancer Properties of Highly Purified l-Asparaginase from Withania somnifera L. against Acute Lymphoblastic Leukemia

Withania somnifera L. has been traditionally used as a sedative and hypnotic. The present study was carried out for the purification, characterization, and in vitro cytotoxicity of l-asparaginase from W. somnifera L. l-Asparaginase was purified from the fruits of W. somnifera L. up to 95% through chromatography. The purified l-asparaginase was characterized by size exclusion chromatography, polyacrylamide gel electrophoresis (PAGE), and 2D PAGE. The antitumor and growth inhibition effect of the l-asparaginase was assessed using [3-(4, 5-dimethyl-thiazol-2yl)-2, 5-diphenyl-tetrazolium bromide] (MTT) colorimetric dye reduction method. The purified enzyme is a homodimer, with a molecular mass of 72 ± 0.5 kDa, and the pI value of the enzyme was around 5.1. This is the first report of the plant containing l-asparaginase with antitumor activity. Data obtained from the MTT assay showed a LD₅₀ value of 1.45 ± 0.05 IU/ml. W. somnifera L. proved to be an effective and a novel source of l-asparaginase. Furthermore, it shows a lot of similarity with bacterial l-asparaginases EC-2.     

Toward the synthesis and biological evaluation of hirsutide

Abstract  The present investigation deals with the synthesis of a N-methylated cyclotetrapeptide, hirsutide (2), by coupling of the dipeptide units Boc-l-phenylalanyl-l-N-methylphenylalanine-OH and l-valyl-l-N-methylphenylalanine-OMe followed by cyclization of the linear tetrapeptide fragment. The chemical structure was established on the basis of analytical as well as spectroscopic data. The newly synthesized cyclic peptide was subjected to pharmacological screening and found to be highly potent against the gram-negative bacteria Pseudomonas aeruginosa and Klebsiella pneumoniae at 6 μg cm⁻³. In addition, potent antihelmintic activity against the earthworms Megascoplex konkanensis and Pontoscotex corethruses at 1 and 2 mg cm⁻³, and potent cytotoxic activity against Dalton’s lymphoma ascites and Ehrlich’s ascites carcinoma cell lines with IC₅₀ values of 14 and 22 μM were also observed. Studies revealed that the pentafluorophenyl ester method employing a catalytic amount of N-methylmorpholine proved to be better for cyclization of the linear tetrapeptide unit. Graphical abstract        

R22(8) motifs in Aminopyrimidine sulfonate/carboxylate interactions: Crystal structures of pyrimethaminium benzenesulfonate monohydrate (2:2:1) and 2-amino-4,6-dimethylpyrimidinium sulfosalicylate dihydrate (4:2:2)

Background  

Pyrimethamine [2,4-diamino-5-(p-chlorophenyl)-6-ethylpyrimidine] is an antifolate drug used in anti-malarial chemotherapy. Pyrimidine and aminopyrimidine derivatives are biologically important compounds owing to their natural occurrence as components of nucleic acids.     

Synthesis of arylaminotetrazoles by ZnCl2/AlCl3/silica as an efficient heterogeneous catalyst

Abstract  

Arylaminotetrazoles were efficiently synthesized from secondary arylcyanamides by application of ZnCl₂/AlCl₃/silica as a reusable heterogeneous Lewis acid catalyst. 5-Arylamino-1H-tetrazoles can be obtained from arylcyanamides carrying electron-withdrawing substituents on the aryl ring, while with electron-releasing groups 1-aryl-5-amino-1H-tetrazoles will be produced. The former isomer is also produced within longer reaction times (~20 h) even with electron-releasing groups.     

KF/Al2O3: an efficient solid heterogeneous base catalyst in one-pot synthesis of benzimidazoles and bis-benzimidazoles at room temperature

Abstract  

KF/Al₂O₃ is an efficient solid heterogeneous base catalyst in the one-pot synthesis of 2-substituted benzimidazoles and 2,2′-disubstituted bis-benzimidazoles from 1,2-phenylenediamines or 3,3′-diaminobenzidines and acid chlorides, anhydrides, and esters at room temperature.     

Determination of D-fagomine in buckwheat and mulberry by cation exchange HPLC/ESI-Q-MS

d-Fagomine is an iminosugar first found in buckwheat (Fagopyrum esculentum Moench) which if used as a dietary supplement or functional food component may reduce the risks of developing insulin resistance, becoming overweight and suffering from an excess of potentially pathogenic bacteria. As d-fagomine may become increasingly important to the food industry, a reliable analytical method for its determination in natural plant sources and foodstuffs is desirable. We have devised a method to separate d-fagomine from its diastereomers 3-epi-fagomine and 3,4-di-epi-fagomine in a single run by cation exchange high-performance liquid chromatography (HPLC) with detection and quantification by mass spectrometry using electrospray ionisation and a simple quadrupole analyser (ESI–Q-MS). The method is validated and applied to the determination of d-fagomine in buckwheat groats (6.7–44 mg kg⁻¹), leaves, bran and flour. We show that buckwheat contains 3,4-di-epi-fagomine (1.0–43 mg kg⁻¹), which has not previously been reported in this source. The procedure is also applied to mulberry (Morus alba) leaves, which contain d-fagomine and 3-epi-fagomine as minor components. The new method provides a means for convenient and accurate determination of d-fagomine in plant samples and foodstuffs.     

FeNH4(SO4)2·12H2O (alum)-catalyzed preparation of 1,4-dihydropyridines: improved conditions for the Hantzsch reaction

Abstract  

FeNH₄(SO₄)₂·12H₂O (alum) efficiently catalyzes the one-pot three-component reaction of dimedone, aldehydes, and 3-aminocrotonate to afford 1,4-dihydropyridines. The work-up is easy, and the products are obtained in good to excellent yields and high purity.