Benzofuranone Derivatives Research Articles

Benzofuranone Derivatives as Effective Small Molecules Related to Insulin Amyloid Fibrillation: A Structure–Function Study

Amyloids are protein fibrils of nanometer size resulting from protein self-assembly. They have been shown to be associated with a wide variety of diseases such as Alzheimer's and Parkinson's and may contribute to various other pathological conditions, known as amyloidoses. Insulin is prone to form amyloid fibrils under slightly destabilizing conditions in vitro and may form amyloid structures when subcutaneously injected into patients with diabetes. There is a great deal of interest in developing novel small molecule inhibitors of amyloidogenic processes, as potential therapeutic compounds. In this study, the effects of five new synthetic benzofuranone derivatives were investigated on the insulin amyloid formation process. Protein fibrillation was analyzed by thioflavin-T fluorescence, Congo red binding, circular dichroism, and electron microscopy. Despite high structural similarity, one of the five tested compounds was observed to enhance amyloid fibrillation, while the others inhibited the process when used at micromolar concentrations, which could make them interesting potential lead compounds for the design of therapeutic antiamyloidogenic compounds.

Synthesis of γ-Benzopyranone by TfOH-Promoted Regioselective Cyclization of o-Alkynoylphenols

Regioselective cyclization of o-alkynoylphenols forming γ-benzopyranones has been demonstrated. Trifluoromethanesulfonic acid (TfOH) induced 6-endo cyclization of o-alkynoylphenols without forming 5-exo cyclized benzofuranone derivatives to provide the corresponding γ-benzopyranones in high yields.

Stability and transformation of major flavonols in onion (Allium cepa) solid wastes

Onion solid wastes were analysed using HPLC and LC / MS and the major polyphenols detected were quercetin, quercetin 4'-O-glucoside, accompanied by protocatechuic acid and a benzofuranone derivative. The latter two compounds have been demonstrated as some of the degradation products that might arise as a result of peroxidase-mediated decomposition of quercetin. These four substances, along with two principal enzymes implicated in flavonols breakdown, β-glycosidase and peroxidise, were monitored throughout an examination period of 48h, in ground onion solid waste. The determinations showed that quercetin 4'-O-glucoside content increased by 13.3%, while quercetin, benzofuranone derivative and protocatechuic acid contents increased by 68.6, 37.5 and 58.4%, respectively. β-Glycosidase activity exhibited fluctuations and increased by 38.2%, whereas the POD showed a constant increasing trend, leading in 21.7% higher activity. On such a ground, a hypothesis was set up to explain transformations of flavonols.

Organocatalytic Asymmetric Conjugate Additions of Oxindoles and Benzofuranones to Cyclic Enones

The asymmetric catalytic synthesis of densely functionalized molecules that contain vicinal quaternary and tertiary stereocenters is a challenge for modern chemical methodology. Here we show that a chiral primary amine, derived from natural molecules, efficiently catalyzes the stereoselective conjugate addition of oxindoles to cyclic enones, leading directly to valuable chiral scaffolds. Proof-of-concept for extending the method to benzofuranone derivatives is also provided.

Structure Effect of Benzofuranone Derivative on the Scavenging Ability to DPPH

Structure Effect of Benzofuranone Derivative on the Scavenging Ability to DPPH

Anionic Cyclization of (N,N-Dimethylamino)[2-(prop-2-yn-1-yloxy)aryl]acetonitriles

The cyclization of (N,N-dimethylamino)[2-(prop-2-yn-1-yloxy)aryl]acetonitriles is carried out under phase-transfer conditions using powdered sodium hydroxide and benzyltriethylammoni- um chloride as catalyst in dimethyl sulfoxide to afford mixtures of a methylenechromane and a methylchromene via favored 6-exo-dig and 6-endo-dig processes, respectively. Several of the chromenes rearranged into benzofuranone derivatives during column chromatography on alumina and the formation of these is rationalized.

Solid Phase Baker–Venkataraman rearrangement under solvent-free condition using grinding technique

Baker–Venkataraman rearrangement of 2-aryloxyacetophenones and 2-cinnamoyloxyacetophenones to 2-hydroxydibenzoylmethanes and 2-hydroxybenzoylcinnamoylmethanes is the key step in the synthesis of flavones and 2-styrylchromones, a class of naturally occurring compounds and several other benzofuranone derivatives. A very simple and highly efficient eco-friendly procedure for Baker–Venkataraman rearrangement has now been developed which involves the grinding of 2-aryloxyacetophenones/2-cinnamoyloxyacetophenones with pulverized potassium hydroxide in a mortar by a pestle and avoids the use of organic solvents at any stage of the reaction.

Synthesis, Binding Affinity, and Molecular Docking Analysis of New Benzofuranone Derivatives as Potential Antipsychotics

The complex etiology of schizophrenia has prompted researchers to develop clozapine-related multitarget strategies to combat its symptoms. Here we describe a series of new 6-aminomethylbenzofuranones in an effort to find new chemical structures with balanced affinities for 5-HT2 and dopamine receptors. Through biological and computational studies of 5-HT2A and D2 receptors, we identified the receptor serine residues S3.36 and S5.46 as the molecular keys to explaining the differences in affinity and selectivity between these new compounds for this group of receptors. Specifically, the ability of these compounds to establish one or two H-bonds with these key residues appears to explain their difference in affinity. In addition, we describe compound 2 (QF1004B) as a tool to elucidate the role of 5-HT2C receptors in mediating antipsychotic effects and metabolic adverse events. The compound 16a (QF1018B) showed moderate to high affinities for D2 and 5-HT2A receptors, and a 5-HT2A/D2 ratio was predictive of an atypical antipsychotic profile.

Unexpected Solvent-Free Cycloadditions of 1,3-Cyclohexanediones to 1-(Pyridin-2-yl)-enones Mediated by Manganese(III) Acetate in a Ball Mill

Under solvent-free ball-milling conditions, manganese(III) acetate dihydrate-mediated cycloadditions of 5,5-dimethyl-1,3-cyclohexanedione and 1,3-cyclohexanedione to various 1-(pyridin-2-yl)-enones proceeded efficiently to afford trans-2-acyl-3-aryl/alkyl-2,3,6,7-tetrahydro-4(5H)-benzofuranone derivatives. The cyclization reactions exhibited good to excellent yields, as well as extremely high diastereoselectivity and unexpected regioselectivity. Manganese(III) acetate behaved both as an oxidant and as a Lewis acid.

Raman and surface-enhanced Raman scattering (SERS) investigation of the quercetin interaction with metals: Evidence of structural changing processes in aqueous solution and on metal nanoparticles

The structural modifications of quercetin (QUC), one of the most common dietary flavonols also used as dye, were investigated in this work at alkaline pH and in the presence of metal ions. The parallel analysis of the Raman and surface-enhanced Raman scattering (SERS) and the UV–vis spectra allowed to demonstrate that the interaction of QUC with Zn(II), Cu(II), or Ag(I) ions can result in the formation of complexes and/or the oxidation of the molecule. The catechol group in the B-ring resulted to be important both for metal chelation and in oxidation processes. In fact, the conversion of this reactive group to o-quinone is the first step of the QUC oxidizing processes which are strongly affected by pH both in the absence and in the presence of metal ions. In alkaline solutions (pH > 9.5) the autoxidation processes of QUC initially lead to the formation of a benzofuranone derivative and, successively, to oligomeric/polymeric species. The QUC oxidation takes place also at lower pH in the presence of metal ions such as silver. In this case, QUC acts only as a reductant and not as a metal-chelating agent. The existence of several condensation pathways was clearly evidenced by the SERS spectra. In fact, depending on pH the interaction of QUC with metal nanoparticles favors one or more polymerization reactions. In particular, the “head to tail” condensations (A-ring of one unit and the B-ring of another) seem to be favored under alkaline conditions.

Reaction of Singlet-Excited 2,3-Diazabicyclo[2.2.2]oct-2-ene and tert-Butoxyl Radicals with Aryl-Substituted Benzofuranones

5,7-Di-tert-butyl-3-aryl-3H-benzofuran-2-ones are lactones with potential antioxidant activity, owing to their abstractable benzylic C-H hydrogens. The fluorescence quenching of the azoalkane 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO), an established probe for the hydrogen-donor propensity of chain-breaking antioxidants, was investigated for 16 aryl-substituted benzofuranone derivatives [m,m-(CF3)2, p-CN, m-CN, p-CF3, p-COOCH3, m-CF3, p-Cl, p-F, H, m-CH3, p-CH3, m,p-(CH3)2, p-OCH3, o-CH3, o-CF3, o,m-(CH3)2]. Analysis of the rate data in terms of a linear free energy relationship yielded a reaction constant of rho = +0.35. This implies that n,pi*-excited DBO acts as nucleophilic species. In contrast, hydrogen abstraction of tert-butoxyl radicals from the benzofuranones was accelerated by electron-donating substituents (rho = -0.23), in conformity with the electrophilic character of oxygen-centered alkoxyl radicals. Possible implications for the optimization of the hydrogen-donor propensity of antioxidants through structural variation are discussed.

Biosynthesis of benzofuran derivatives in root cultures of Tagetes patula via phenylalanine and 1-deoxy- d-xylulose 5-phosphate

Root cultures of Tagetes patula L. cv. Carmen were grown with a mixture of unlabeled glucose and [U- 13C 6]glucose or [1- 13C 1]glucose as carbon source. Isoeuparin and (−)-4-hydroxytremetone were isolated by solvent extraction of the cultured tissue, purified by chromatography and analysed by 1H and 13C NMR spectroscopy. Amino acids obtained by hydrolysis of protein from the same experiments were used for the reconstruction of the labelling patterns in central metabolic intermediates. These labelling patterns were used for the prediction of isotopolog compositions in the benzofuranone derivatives via different hypothetical pathways. Comparison with the experimentally observed isotopolog distributions showed that the benzenoid ring and the acetoxy group are exclusively or predominantly (>98%) derived from phenylalanine and not from acetyl-CoA via a polyketide-type biosynthesis. The isopropylidene side chain and two carbon atoms of the furan and dihydrofuran moiety, respectively, originate from an isoprenoid building block obtained exclusively or predominantly (>98%) via the deoxyxylulose phosphate pathway. The exomethylene atom of the isopropylidene side chain is biosynthetically equivalent to the ( Z)-methyl group of dimethylallyl diphosphate. The data indicate that isoeuparin and (−)-4-hydroxytremetone are assembled from 4-hydroxyacetophenone and dimethylallyl diphosphate via prenyl-substituted 4-hydroxyacetophenone and dihydrobenzofurans as intermediates.

Condensation of p‐Benzoquinone with Anilides of β‐Aminocrotonic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Condensation ofp-Benzoquinone with Anilides of -Aminocrotonic Acid

Benzofuranone derivatives have been synthesized by the condensation of p-benzoquinone with anilides of β-aminocrotonic acids under the conditions of the Nenitzescu reaction.

Studies on Synthesis of 3(2H)‐Benzofuranone Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

STUDIES ON SYNTHESIS OF 3(2H)-BENZOFURANONE DERIVATIVES

ABSTRACT Two known methods were used for synthesis of 2,6-disubstituted-3(2H)-benzofuranone derivatives. It was found that depending on the reaction conditions, degradation products or the products of oxidation were isolated. This latter reaction became the main process when the ring closure was performed starting from methoxy- or 2-propoxy-desoxybenzoin and diethyl bromo-(or chloro-)-malonate to give d,l- and meso-dimers of the substituted 3(2H)-benzofuranones.

ChemInform Abstract: Electrolytic Partial Fluorination of Organic Compounds. Part 36. Regioselective Anodic Fluorination of Phenylthiolated Benzofuranone and Benzothiazole Derivatives.

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Electrolytic partial fluorination of organic compounds. 36 . Regioselective anodic fluorination of phenylthiolated benzofuranone and benzothiazole derivatives

The anodic fluorination of 3-phenylthio-2-benzofuranones and α-phenylthio-2-benzothiazolylacetonitrile was investigated. Both derivatives were selectively fluorinated in good yields at the carbon α to the sulfur atoms in Et 4NF·3HF/DME using a platinum anode and an undivided cell. The fluorination yields of the benzofuranone derivatives were improved by the addition of Ph 2S, which was not effective in the case of the benzothiazole derivative. The fluorination yield of the benzothiazole derivative was strongly affected by the stirring state of the electrolytic solution or the applied anode potential.

ChemInform Abstract: Generation of Radical Species from Cyclohexane‐1,2‐dione and the Reaction with Olefins: Preparation of 4,5‐Dihydro‐7(6H)‐benzofuranone Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Generation of Radical Species from Cyclohexane-1,2-dione and the Reaction with Olefins: Preparation of 4,5-Dihydro-7(6H)-benzofuranone Derivatives

Abstract Oxidation of cyclohexane-1,2-dione with ammonium hexanitratocerate(IV) (CAN) generates 2,3-dioxocyclohexyl radical, which reacts with electron-rich olefins to afford the corresponding addition products. The adducts thus generated are converted to 4,5-dihydro-7(6H)-benzofuranone by acid treatment. In addition to cyclohexane-1,2-dione, radical species are also generated from cyclopentane-1,2-dione and cycloheptane-1,2-dione.