Synthesis, characterization, and antioxidant activity of some ebselen analogues

Simple synthetic routes for several analogues of the anti-inflammatory organoselenium drug, ebselen, are described. The compounds are characterized by (1)H, (13)C, and (77)Se NMR spectroscopy and mass spectral techniques and, in some cases, by single-crystal X-ray diffraction studies. The glutathione peroxidase (GPx)-like antioxidant activity has been studied by using H(2)O(2), tBuOOH, and Cum-OOH as substrates, and thiophenol (PhSH, 4-Me-C(6)H(4)SH) and glutathione (GSH) as cosubstrates. Density functional theory (DFT) calculations have been performed on these systems to understand the effects of various substituents on the (77)Se NMR chemical shifts; these results have been compared with the experimental data. The experimental and theoretical results suggest that the presence of a phenyl substituent on the nitrogen atom is important for the antioxidant activity of ebselen. While ebselen and its analogues are poor catalysts in aromatic thiol assays, these compounds exhibit high GPx activity when GSH is used as the cosubstrate. The poor catalytic activity of ebselen analogues in the presence of aromatic thiols such as PhSH and 4-Me-C(6)H(4)SH can be ascribed to the undesired thiol exchange reaction that takes place at the selenium center due to SeO nonbonding interactions. To understand the effects of different peroxides on the catalytic activities, we have determined the initial rates at various concentrations of GSH and peroxides. These data suggest that the nature of peroxide has little effect on the catalytic efficiencies, although the initial reaction rates observed with hydrogen peroxide were found to be higher than that with tBuOOH and Cum-OOH. In contrast to the effect of peroxides, the nature of thiols appears to have a dramatic effect on the catalytic activity of ebselen and its related derivatives.     

Synthesis, structure, and glutathione peroxidase-like activity of amino acid containing ebselen analogues and diaryl diselenides

The synthesis of some ebselen analogues and diaryl diselenides, which have amino acid functions as an intramolecularly coordinating group (Se···O) has been achieved by the DCC coupling procedure. The reaction of 2,2'-diselanediylbis(5-tert-butylisophthalic acid) or the activated ester tetrakis(2,5-dioxopyrrolidin-1-yl) 2,2'-diselanediylbis(5-tert-butylisophthalate) with different C-protected amino acids (Gly, L-Phe, L-Ala, and L-Trp) afforded the corresponding ebselen analogues. The used precursor diselenides have been found to undergo facile intramolecular cyclization during the amide bond formation reaction. In contrast, the DCC coupling of 2,2'-diselanediyldibenzoic acid with C-protected amino acids (Gly, L/D-Ala and L-Phe) affords the corresponding amide derivatives and not the ebselen analogues. Some of the representative compounds have been structurally characterized by single-crystal X-ray crystallography. The glutathione peroxidase (GPx)-like activities of the ebselen analogues and the diaryl diselenides have been evaluated by using the coupled reductase assay method. Intramolecularly stabilized ebselen analogues show slightly higher maximal velocity (V(max)) than ebselen. However, they do not show any GPx-like activity at low GSH concentrations at which ebselen and related diselenides are active. This could be attributed to the peroxide-mediated intramolecular cyclization of the corresponding selenenyl sulfide and diaryl diselenide intermediates generated during the catalytic cycle. Interestingly, the diaryl diselenides with alanine (L,L or D,D) amide moieties showed excellent catalytic efficiency (k(cat)/K(M)) with low K(M) values in comparison to the other compounds.     

Selective conversion of {Mo132} Keplerate ion into 4-electron reduced crown-capped Keggin derivative [Te5Mo15O57](8-). A key intermediate to single-phase M1 multielement MoVTeO light-alkanes oxidation catalyst

{Mo(132)} Keplerate anion reacts with tellurites to give a soluble precursor to produce in hydrothermal conditions single-phase M1 MoVTeO light-alkanes oxidation catalyst. Characterization of this Te-containing intermediate by single-crystal X-ray diffraction, (125)Te NMR, UV-visible and redox titration reveals a molybdotellurite anion as a crown-capped Keggin derivative.     

Acidity trends in alpha,beta-unsaturated sulfur, selenium, and tellurium derivatives: comparison with C-, Si-, Ge-, Sn-, N-, P-, As-, and Sb-containing analogues

The gas-phase acidity of CH3-CH2XH (X=S, Se, Te), CH2=CHXH (X=S, Se, Te) and PhXH (X=S, Se) compounds was measured by means of Fourier transform ion cyclotron resonance mass spectrometry. To analyze the role that unsaturation plays on the intrinsic acidity of these systems, a parallel theoretical study, in the framework of the G2 and the G2(MP2) theories, was carried out for all ethyl, ethenyl (vinyl), ethynyl, and phenyl O-, S-, Se-, and Te-containing derivatives. Unsaturated compounds are stronger acids than their saturated analogues, because of the strong pi-electron donor ability of the heteroatoms that contributes to a large stabilization of the unsaturated anions. Ethynyl derivatives are stronger acids than vinyl compounds, while phenyl derivatives have an intrinsic acidity intermediate between that of the corresponding vinyl and ethynyl analogues. The CH2=CHXH vinyl compounds (enol-like) behave systematically as slightly stronger acids than their CH3-C(H)X (keto-like) tautomers. Vinyl derivatives are stronger acids than ethyl compounds, because the anion stabilization attributable to unsaturation is greater than that undergone in the neutral compounds. Conversely, the enhanced acidity of the ethynyl derivatives with respect to the vinyl compounds is due to two concomitant effects, the stabilization of the anion and the destabilization of the neutral compound. The acidities of ethyl, vinyl, and ethynyl derivatives containing heteroatoms of Groups 14, 15, and 16 of the periodic table are closely related, and reflect the differences in electronegativity of the CH3CH2-, CH2=CH-, and CH[triple chemical bond]C- groups.     

Novel multicomponent reactions of primary amines and alkyl propiolates with alloxan derivatives in water

A water-accelerated multicomponent synthesis of organic target molecules has been used as a key method for the preparation of novel barbiturate derivatives. The three-component condensation reactions of primary amines with alkyl propiolates in the presence of alloxan derivatives in water are developed as efficient and clean green synthetic procedures for the high-yielding preparation of alkyl 2-(5-hydroxy-2,4,6-trioxohexahydro-5-pyrimidinyl)-3-(alkyl or arylamino)-2-propenoates. The above synthetic protocol provides rapid access to novel and diversely substituted barbiturate derivatives.     

Synthesis of Cd-free water-soluble ZnSe(1-x)Te(x) nanocrystals with high luminescence in the blue region

Cd-free core-shell nanocrystals (ZnSe(1-x)Te(x)/ZnS, 0相似文献   

Modeling the reduction of hydrogen peroxide by glutathione peroxidase mimics

Theoretical calculations have been performed on three model reactions representing the reduction of hydrogen peroxide by ebselen, ebselen selenol, and ebselen diselenide. The reaction surfaces have been investigated at the B3PW91/6-311G(2df,p) level, and single-point energies were calculated using the 6-311++G(3df,3pd) basis set. Solvent effects were included implicitly with the conductor-like polarizable continuum model and in one case with explicit inclusion of three water molecules. Mechanistic information is gained from investigating the critical points using the quantum theory of atoms in molecules. The barriers for the reduction of hydrogen peroxide with the ebselen, ebselen selenol, and ebselen diselenide models are 56.7, 53.4, and 35.3 kcal/mol, respectively, suggesting that ebselen diselenide may be the most active antioxidant in the ebselen GPx redox pathway. Results are also compared to that of the sulfur analogues of the model compounds.     

噻吩并噻吩的合成研究

噻吩并噻吩自1886年以来一直是化学研究的对象, 综述了经典稠合噻吩并噻吩的合成方法. 对一般的合成方法及原始地制备某一类特定化合物的方法都作了简要讨论.     

The role of chalcogen-chalcogen interactions in the intrinsic basicity acidity of beta-chalcogenovinyl(thio)aldehydes HC([double bond]X)[bond]CH[double bond]CH[bond]CYH

The intrinsic acidity and basicity of a series of beta-chalcogenovinyl(thio)aldehydes HC([double bond]X)[bond]CH[double bond]CH[bond]CYH (X=O, S; Y=Se, Te) were investigated by B3LYP/6-311+G(3df,2p) density functional and G2(MP2) calculations on geometries optimized at the B3LYP/6-31G(d) level for neutral molecules and at the B3LYP/6-31+G(d) level for anions. The results showed that selenovinylaldehyde and selenovinylthioaldehyde should behave as Se bases in the gas phase, because the most stable neutral conformer is stabilized by an X[bond]H...Se (X=O, S) intramolecular hydrogen bond (IHB). In contrast the Te-containing analogues behave as oxygen or sulfur bases, because the most stable conformer is stabilized by typical X...Y[bond]H chalcogen-chalcogen interactions. These compounds have a lower basicity than expected because either chalcogen-chalcogen interactions or IHBs become weaker upon protonation. Similarly, they are also weaker acids than expected because deprotonation results in a significantly destabilized anion. Loss of the proton from the X[bond]H or Y[bond]H groups is a much more favorable than from the C[bond]H groups. Therefore, for Se compounds the deprotonation process results in loss of the X[bond]H...Se (X=O, S) IHBs present in the most stable neutral conformer, while for Te-containing compounds the stabilizing X...Y[bond]H chalcogen-chalcogen interaction present in the most stable neutral conformer becomes repulsive in the corresponding anion.     

Effect of substituents on the GPx-like activity of ebselen: steric versus electronic

The direct oxidation of ebselen and several derivatives by hydrogen peroxide is investigated using the B3LYP/6-31G(d,p) method to elucidate the effects of substituents on GPx-like activity. While previous studies have attributed the differences in GPx activity of substituted ebselen compounds to the electronic nature of the substituents, the influence of functional groups is poorly understood. The effects of various solvents are incorporated by employing the CPCM method. It is shown that a substituent in the ortho position to the selenium atom sterically hinders attack of a nucleophile at selenium and thus increases the barrier to reaction. The observed increase in GPx-like activity of an ebselen derivative with an ortho substituent is explained by the fact that the steric hindrance prevents thiol exchange reactions.     

Preparation of Synthetic and Natural Derivatives of Flavonoids Using Suzuki–Miyaura Cross-Coupling Reaction

Herein, we report the use of the Suzuki–Miyaura cross-coupling reaction for the preparation of a library of synthetic derivatives of flavonoids for biological activity assays. We have investigated the reactivity of halogenated flavonoids with aryl boronates and with boronyl flavonoids. This reaction was used to prepare new synthetic derivatives of flavonoids substituted at C-8 with aryl, heteroaryl, alkyl, and boronate substituents. The formation of flavonoid boronate enabled a cross-coupling reaction with halogenated flavones yielding biflavonoids connected at C-8. This method was used for the preparation of natural compounds including C-8 prenylated compounds, such as sinoflavonoid NB. Flavonoid boronates were used for the preparation of rare C-8 hydroxyflavonoids (natural flavonoids gossypetin and hypolaetin). A series of previously unknown derivatives of quercetin and luteolin were prepared and fully characterized.     

Density functional theory study of the reaction mechanism and energetics of the reduction of hydrogen peroxide by ebselen, ebselen diselenide, and ebselen selenol

Density functional theory calculations at the B3LYP/6-311++G(3df,3pd)//B3LYP/6-31G(d,p) level have been performed to elucidate the mechanism and reaction energetics for the reduction of hydrogen peroxide by ebselen, ebselen diselenide, ebselen selenol, and their sulfur analogues. The effects of solvation have been included with the CPCM model, and in the case of the selenol anion reaction, diffuse functions were used on heavy atoms for the geometry optimizations and thermochemical calculations. The topology of the electron density in each system was investigated using the quantum theory of atoms in molecules, and a detailed interpretation of the electronic charge and population data as well as the atomic energies is presented. Reaction free energy barriers for the oxidation of ebselen, ebselen diselenide, and ebselen selenol are 36.8, 38.4, and 32.5 kcal/mol, respectively, in good qualitative agreement with experiment. It is demonstrated that the oxidized selenium atom is significantly destabilized in all cases and that the exothermicity of the reactions is attributed to the peroxide oxygen atoms via reduction. The lower barrier to oxidation exhibited by the selenol is largely due to entropic effects in the reactant complex.     

磷钨杂多酸一步法催化合成芳香基脂肪酸

 首次提出用杂多酸为催化剂,利用芳烃及其衍生物和不饱和酸的傅-克烷基化反应一步合成相应的芳基脂肪酸,缩短了合成路线,同时避免了以往非绿色化的AlCl3催化合成.     

Synthesis of Imidazolato and 2-Methyl-Imidazolato Derivatives of Tellurium(IV)

INTRODUCTION

The chemistry of S-N compounds has been well established^[1] in the past few years and the stability was accounted in terms of extensive π bonding^[2,3]. The diversity of these compounds tempted chemsits to explore analogous Se-N and Te-N compounds. However, the poor or even absence of π bonding with heavier Se and Te posed problem to synthesize such compounds in the past. The chemistry of Se-N and Te-N compounds has been developed extensively by introducing new synthetic precursors^[4] in the last decade or so. We have observed that N-trimethyl silylimidazole and 2-methyl silylimidazole are potential reagents for peperation of monomeric transition metal imidazolates and Tin(IV) imidazolate^[5,6]. We, therefore, thought worthwhile to synthesize amido derivatives of Te(IV) incorporating these π delocalised heterocycles which acts as potential 4e (both σ and π) donors.     

Synthesis and biological evaluation of ebselen and its acyclic derivatives

Five ebselen and three acyclic ebselen derivatives were synthesized. These compounds were screened for their glutathione peroxidase (GSH Px)-like activity and scavenging activity against 1,1-diphenyl-2-pycryl-hydrazyl (DPPH) and peroxynitrite radical. All tested compounds displayed similar significant GSH Px-like activity, which are slightly higher than that of ebselen. The peroxynitrite scavenging activity showed that the acyclic allylseleno 4c was five times more potent than ebselen.     

Highlights on Steroidal Arylidene Derivatives as a Source of Pharmacologically Active Compounds: A Review

Steroids constitute a unique class of chemical compounds, playing an important role in physiopathological processes, and have high pharmacological interest. Additionally, steroids have been associated with a relatively low toxicity and high bioavailability. Nowadays, multiple steroidal derivatives are clinically available for the treatment of numerous diseases. Moreover, different structural modifications on their skeleton have been explored, aiming to develop compounds with new and improved pharmacological properties. Thus, steroidal arylidene derivatives emerged as a relevant example of these modifications. This family of compounds has been mainly described as 17β-hydroxysteroid dehydrogenase type 1 and aromatase inhibitors, as well as neuroprotective and anticancer agents. Besides, due to their straightforward preparation and intrinsic chemical reactivity, steroidal arylidene derivatives are important synthetic intermediates for the preparation of other compounds, particularly bearing heterocyclic systems. In fact, starting from arylidenesteroids, it was possible to develop bioactive steroidal pyrazolines, pyrazoles, pyrimidines, pyridines, spiro-pyrrolidines, amongst others. Most of these products have also been studied as anti-inflammatory and anticancer agents, as well as 5α-reductase and aromatase inhibitors. This work aims to provide a comprehensive overview of steroidal arylidene derivatives described in the literature, highlighting their bioactivities and importance as synthetic intermediates for other pharmacologically active compounds.     

Exploring the Chemistry of Non-sticky Sugars: Synthesis of Polyfluorinated Carbohydrate Analogues of d-Allopyranose

There is a growing interest in the preparation of polyfluorinated carbohydrates. A limited number of fluorohexopyranosides have been used in biological investigations because of the synthetic challenge they present. Hence, we report the synthesis of fluorinated homodimer, fluorodisaccharides, C-terminal fluoroglycopeptides, lipoic acid fluoroglycoconjugate and trifluoroallopyranoside derivatives functionalized at C-6. Our strategy uses levoglucosan as inexpensive starting material and facilitates an approach to complex carbohydrate analogues with multiple C−F bonds. The challenge of our synthetic route centered around an efficient preparation of crucial 1,6-anhydro-2,4-dideoxy-difluoroglucopyranose and focused on achieving a difficult glycosylation of the trifluoroallopyranose donor. The results clearly highlight challenges related to the preparation of polyhalogenated complex organic molecules and pave the way to access novel medically relevant tools.     

Convenient synthesis of 2-(methylsulfonyl)pyrimidine derivatives

An efficient and convenient approach for the preparation of functionalized 2-(methylsulfonyl)pyrimidine derivatives has been developed through cyclic condensation of malonate derivatives with S-methylisothiouronium sulfate followed by derivation and oxidation in water–acetone mixture using oxone as the oxidant. This synthetic strategy provides an efficient and environmentally friendly approach for easy access to 2-(methylsulfonyl)pyrimidine derivatives with considerable yields.     

Coordination chemistry of 2,4,6-tri(pyridyl)-1,3,5-triazine ligands

This review covers the rich coordination chemistry of 2,4,6-tri(pyridyl)-1,3,5-triazine ligands. These polypyridyl derivatives have been coupled to transition metals and lanthanides, and the complexes obtained have been used in various fields such as luminescent materials, for the preparation of coordination polymers and networks as well as for the synthesis of discrete metalla-assemblies. The synthetic and structural aspects of the different isomers of 2,4,6-tri(pyridyl)-1,3,5-triazine are presented, and a survey of their coordination chemistry is given.     

Ortho-tellurated derivatives of some arylamines and imines

A range of novel bi-, tri- and multidentate organotellurium ligands containing Te and N donor atoms and their derivatives have been synthesised. The synthetic strategy involves telluration of orthochelating, monoanionic substrates derived from the following arylamines: N,N-dimethylbenzylamine, (S)-(-)-N,Ndimethyl-1-phenethylamine, N,N-dimethylnaphthylamine, (N,N-di-methylaminomethy l) ferrocene, tricarbony1(N, N-dimethylbenzenemethanamine) chromium and 2-(3-thienyl)-pyridine. In addition novel chiral hybrid Schiff base ligands have been prepared by the condensation reaction of bis(o-formylphenyl) telluride ando-butyltellurobenzaldehyde with (R)-(+)-l-phenethylamine and (1R, 2S)-(-)-norephedrine.