- Synthesis, photophysical and electrochemical properties of novel and highly fluorescent difluoroboron flavanone β-diketonate complexes
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Difluoroboron β-diketonates complexes are highly luminescent with extensive properties such as their fluorescence both in solution and in solid state and their high molar extinction coefficients. Due to their rich optical properties, these compounds have been studied for their applications in organic electronics such as in self-assembly and applications in biosensors, bio-imaging and optoelectronic devices. The easy and fast synthesis of difluoroboron β-diketonate (BF2dbm) complexes makes their applications even more attractive. Although many different types of difluoroboron β-diketonates complexes have been studied, the cyclic flavanone analogues of these compounds have never been reported in the literature. Therefore, the present work aims to synthesize difluouroboron flavanone β-diketonate complexes, study their photophysical and electrochemical properties and assess their suitability for applications in optoelectronic devices. The synthesis was based on a Baker-Venkataraman reaction which initially provided substituted diketones, which were subsequently reacted with aldehydes to afford the proposed flavanones. The complexation was achieved by reacting flavanones and BF3·Et2O and in total 9 novel compounds were obtained. A representative difluoroboron flavanone complex was subjected to single crystal X-ray diffraction to unequivocally confirm the chemical structure. A stability study indicated only partial degradation of these compounds over a few days in a protic solvent at elevated temperatures. Photophysical studies revealed that the substituent groups and the solvent media significantly influence the electrochemical and photophysical properties of the final compounds, especially the molar absorption coefficient, fluorescence quantum yields, and the band gap. Moreover, the compounds exhibited a single excited-state lifetime in all studied solvents. Computational studies were employed to evaluate ground and excited state properties and carry out DFT and TDDFT level analysis. These studies clarify the role of each state in the experimental absorption spectra as well as the effect of the solvent.
- Paez, Elida Betania Ariza,Curcio, Sergio,Neme, Natália P.,Matos, Matheus J. S.,Correa, Rodrigo S.,Pereira, Fabio Junio,Hilário, Flaviane Francisco,Cazati, Thiago,Taylor, Jason Guy
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- Synthesis of 2,2′-biflavanones from flavone via electrolytic reductive coupling
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Flavone (1) was easily reduced by using the electrochemical method to give two hydrodimers of 2,2′-biflavanone(racemate) (5a) and 2,2′-biflavanone(meso) (5b) and one reductive product of flavanone (6). Their yields were dependent on the nature of electrodes, the kinds of supporting electrolytes and the reaction temperature. They were found to afford higher yields of 2,2′-biflavanone(racemate) (5a) and 2,2′-biflavanone (meso) (5b) (32.4% and 24.8%, 35.8% and 13.4%, respectively,) in the reaction conditions of Pb(-)/C(+)-H2SO4-TF/mol and C(-)/C(+)-H 2SO4-5F/mol.
- Chen, Arh-Hwang,Cheng, Chieh-Yuan,Chen, Chia-Wen
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- Catalytic and stoichiometric flavanone oxidation mediated by nonheme oxoiron(iv) complexes as flavone synthase mimics: Kinetic, mechanistic and computational studies
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The present study describes the first example of the stoichiometric and catalytic oxidation of flavanone by synthetic nonheme oxoiron(iv) complexes and their precursor iron(ii) complexes with m-CPBA as the terminal oxidant. These models, including detailed kinetic, mechanistic and computational studies, may serve as the biomimics of flavone synthase (FS) enzymes.
- Turcas, Ramona,Kripli, Balázs,Attia, Amr A. A.,Lakk-Bogáth, Dóra,Speier, Gábor,Giorgi, Michel,Silaghi-Dumitrescu, Radu,Kaizer, József
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Read Online
- Synthesis, structure and acetylcholinesterase inhibition activity of new diarylpyrazoles
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A variety of diarylpyrazole derivatives III-VI were synthesized and structurally characterized using FTIR, 1H and 13C NMR spectroscopy, and in case of compound VIb by X-ray single crystal analysis. The in vitro biological studies rev
- Arshad, Iqra,Dege, Necmi,Hameed, Shahid,Kharl, Aamir Ali,Nadeem, Humaira,Naseer, Muhammad Moazzam,Paracha, Rehan Zafar,Zia, Mehwash
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- In vitro photoprotective evaluation and development of novel nanoemulsion with chromone derivative
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Chromone derivatives exhibiting high absorbance values in the UVA/UVB region were synthesized, and their photoprotective properties were evaluated. Chromones were prepared according to known literature procedures and characterized by high resolution mass
- Amparo, Tatiane R.,Antunes, Amanda S.,Cazati, Thiago,Diogo, Gabriela M.,Dos Santos, Viviane M. R.,Gouveia, Ana Paula,Penido, Ricardo G.,Perasoli, Fernanda B.,Sousa, Lucas R. D.,Taylor, Jason G.,Vieira, Paula M. A.,dos Santos, Orlando D. H.
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p. 1813 - 1821
(2021/08/05)
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- Comparison of nonheme manganese‐ and iron‐containing flavone synthase mimics
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Heme and nonheme‐type flavone synthase enzymes, FS I and FS II are responsible for the synthesis of flavones, which play an important role in various biological processes, and have a wide range of biomedicinal properties including antitumor, antimalarial, and antioxidant activities. To get more insight into the mechanism of this curious enzyme reaction, nonheme structural and functional models were carried out by the use of mononuclear iron, [FeII(CDA‐BPA*)]2+ (6) [CDA‐BPA = N,N,N’,N’‐tetrakis‐(2‐pyridylmethyl)‐cyclohexanediamine], [FeII(CDA‐BQA*)]2+ (5) [CDA‐BQA = N,N,N’,N’‐tetrakis‐(2‐quinolilmethyl)‐cyclohexanediamine], [FeII(Bn‐TPEN)(CH3CN)]2+ (3) [Bn‐ TPEN = N‐benzyl‐N,N’,N’‐tris(2‐pyridylmethyl)‐1,2‐ diaminoethane], [FeIV(O)(Bn‐TPEN)]2+ (9), and manganese, [MnII(N4Py*)(CH3CN)]2+ (2) [N4Py* = N,N‐bis(2‐pyridylmethyl)‐1,2‐di(2‐pyridyl)ethyl-amine)], [MnII(Bn‐TPEN)(CH3CN)]2+ (4) complexes as catalysts, where the possible reactive inter-mediates, high‐valent FeIV(O) and MnIV(O) are known and well characterised. The results of the catalytic and stoichiometric reactions showed that the ligand framework and the nature of the metal cofactor significantly influenced the reactivity of the catalyst and its intermediate. Comparing the reactions of [FeIV(O)(Bn‐TPEN)]2+ (9) and [MnIV(O)(Bn‐TPEN)]2+ (10) towards flavanone under the same conditions, a 3.5‐fold difference in reaction rate was observed in favor of iron, and this value is three orders of magnitude higher than was observed for the previously published [FeIV(O)(N2Py2Q*)]2+ [N,N‐bis(2‐quinolylmethyl)‐1,2‐di(2‐pyridyl)ethylamine] species.
- Juraj, Natalija Pantalon,Kaizer, József,Kirin, Sre?ko I.,Lakk‐bogáth, Dóra,Meena, Bashdar I.,Peri?, Berislav
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- Trypanocidal activity of flavanone derivatives
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Chagas disease, also known as American trypanosomiasis, is classified as a neglected disease by the World Health Organization. For clinical treatment, only two drugs have been on the market, Benznidazole and Nifurtimox, both of which are recommended for use in the acute phase but present low cure rates in the chronic phase. Furthermore, strong side effects may result in discontinuation of this treatment. Faced with this situation, we report the synthesis and trypanocidal activity of 3-benzoyl-flavanones. Novel 3-benzoyl-flavanone derivatives were prepared in satisfactory yields in the 3-step synthetic procedure. According to recommended guidelines, the whole cell-based screening methodology was utilized that allowed for the simultaneous use of both parasite forms responsible for human infection. The majority of the tested compounds displayed promising anti-Trypanosoma cruzi activity and the most potent flavanone bearing a nitrofuran moiety was more potent than the reference drug, Benznidazole.
- Andrade, Josimara Souza,Diogo, Gabriela Maciel,Dos Santos, Viviane Martins Rebello,Murta, Silvane Maria Fonseca,Sales, Policarpo Ademar,Taylor, Jason Guy
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- Novel Bifunctionalization of Activated Methylene: Base-Promoted Trifluoromethylthiolation of β-Diketones with Trifluoromethanesulfinyl Chloride
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A novel bifunctionalization of activated methylene was achieved successfully through the base-promoted trifluoromethylthiolation of β-diketones or β-ketoesters with trifluoromethanesulfinyl chloride. A series of α-trifluoromethylthiolated α-chloro-β-diketones and α-chloro-β-ketoesters were obtained in moderate to good yields under mild conditions. When β-diketones containing a phenyl group with a hydroxyl or amino substituent at the ortho position were used as substrates, intramolecular trifluoromethylthiolation/cyclization reaction took place to give the corresponding cyclic products. Furthermore, the protocol could be extended to perfluoroalkylthiolation with the sodium perfluoroalkanesulfinate/POCl3 system. On the basis of experimental results, plausible mechanisms are proposed.
- Sun, Dong-Wei,Jiang, Min,Liu, Jin-Tao
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supporting information
p. 10797 - 10802
(2019/07/03)
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- Rh(III)-Catalyzed Aldehydic C?H Functionalization Reaction between Salicylaldehydes and Sulfoxonium Ylides
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A novel aldehydic C?H functionalization reaction between salicylaldehydes and sulfoxonium ylides has been developed under rhodium(III) catalysis, affording coupling products in moderate to good yields. A plausible mechanism involving aldehydic C(sp2)?H activation by rhodium(III) and rhodium(III) catalyzed carbene insertion is also proposed. It was also found that the aldehydic C?H functionalization followed by dehydrative cyclization was able to produce flavonoids in one-pot. (Figure presented.).
- Xu, Guo-Dong,Huang, Kenneth L.,Huang, Zhi-Zhen
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supporting information
p. 3318 - 3323
(2019/06/25)
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- Method for synthesizing 2-aryl benzopyrone flavonoid derivatives
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The invention relates to a method for synthesizing 2-aryl benzopyrone flavonoid derivatives, and relates to a method for synthesizing a compound, the method for synthesizing 2-aryl benzopyrone flavonoid derivatives is suitable for the synthesis of 2-aryl benzopyrone flavonoid derivatives containing different substituents. The method aims to solve the technical problems of low yield, long reactionperiod, and complicated post-treatment and high operation difficulty of the existing synthesis method of the ketone flavonoid derivative. The method comprises the following steps of: 1, preparing beta-propanedione compounds; 2, preparing flavonoid compound 2-aryl benzopyranones. The method completes esterification and rearrangement in one step, which is simple and practical, reduces intermediate links of reaction, saves separation and purification of intermediate products, improves utilization rate of raw materials, reduces reaction temperature, shortens reaction time under microwave radiation, reduces solvent consumption, the post-treatment is relatively simple, the yield is relatively high and no by-products exist, and can also react in the presence of a small amount of water, the reaction is easy to operate, and the method is suitable for industrial production. The method belongs to the technical field of compound synthesis.
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Paragraph 0050; 0051 0052
(2019/04/30)
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- Design, synthesis and biological evaluation of 2-Phenyl-4H-chromen-4-one derivatives as polyfunctional compounds against Alzheimer’s disease
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Polyfunctional compounds comprise a novel class of therapeutic agents for the treatment of multi-factorial diseases. A series of 2-Phenyl-4H-chromen-4-one and its derivatives (5a–n) were designed, synthesized, and evaluated for their poly-functionality against acetylcholinestrase (AChE) and advanced glycation end products (AGEs) formation inhibitors against Alzheimer’s disease (AD). The screening results showed that most of them exhibited a significant ability to inhibit AChE AGEs formation with additional radical scavenging activity. Especially, 5m, 5b, and 5j displayed the greatest ability to inhibit AChE (IC50 = 8.0, 8.2, and 11.8 nM, respectively) and AGEs formation (IC50 = 55, 79, and 54 μM, respectively) with good antioxidant activity. Molecular docking studies explored the detailed interaction pattern with active, peripheral, and mid-gorge sites of AChE. These compounds, exhibiting such multiple pharmacological activities, can be further taken a lead for the development of potent drugs for the treatment of Alzheimer’s disease.
- Singh, Manjinder,Kaur, Maninder,Vyas, Bhawna,Silakari, Om
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p. 520 - 530
(2017/10/09)
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- Rational design for multicolor flavone-based fluorophores with aggregation-induced emission enhancement characteristics and applications in mitochondria-imaging
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Fluorophores with aggregation-induced emission enhancement (AIEE) properties have attracted more attention in recent years. In order to realise more valuable applications, the different kinds of AIEE molecules are in serious need of further development. Therefore, a novel flavone-based AIEE system derived from restriction of intramolecular rotation (RIR) was designed and synthesized in this work. The results revealed that six of the compounds showed typical AIEE characteristics, with fluorescence emissions from purple, blue, cyan to green, tunable by changing substituent groups. This flavone-based AIEE system has never been reported before. The AIEE characteristics were investigated by optical spectroscopy, fluorescence photographs, scanning electron microscopy (SEM), fluorescence quantum yields (φF) and fluorescence lifetime in the CH3OH/H2O mixed solution. Moreover, benefiting from the simple structures and small molecular weight, they could permeate cells faster than current high-molecular-weight AIEE molecules. Furthermore, to examine possible biomedical applications, fluorescence imaging in living A549 lung cells and cell viabilities were examined, and the results displayed that these fluorophores showed good cellular uptake and low cytotoxicity within the experimental concentration range. In addition, these AIEE compounds possessed excellent specificity for mitochondrial targeting and mitochondrial morphological change tracking, besides, they displayed superior photostability, which indicated they are potential candidates for mitochondrial imaging.
- Liu, Liyan,Lei, Yaohui,Zhang, Jianhui,Li, Na,Zhang, Fan,Wang, Huaqiao,He, Feng
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- Green and efficient synthesis of flavones and chromones using heteropolyacids as catalyst in glycerol
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Organic solvents are required to carry out most organic transformations, which cause environmental pollution because of their low volatility. Glycerol, a side product obtained from biodiesel production, has emerged as a friendly solvent due to its advantageous properties. In this paper, an efficient procedure for the synthesis of flavones and chromones, using heteropolyacids as recyclable catalyst and glycerol as the solvent, is presented. The use of heteropolyacids as catalysts allows for excellent yields, easy separation and recovery, low environmental impact, and low cost. Glycerol can also be readily recovered and used over again. In addition, the presented method provides other advantages such as the low formation of waste and the replacement of corrosive mineral acids.
- Migliorero, María Belén Colombo,Palermo, Valeria,Durango, Edwin Alexis Alarcón,Holguín, Aída Luz Villa,Vázquez, Patricia Graciela,Sathicq, ángel Gabriel,Romanelli, Gustavo Pablo
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p. 826 - 832
(2018/11/06)
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- Pd/C: An efficient and reusable catalyst for the synthesis of flavones via carbonylation of aryl halides
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This work describes an efficient and mild approach for the synthesis of flavones via catalytic carbonylation of aryl halides with 2-hydroxyacetophenone using the commercial Pd/C as an efficient, heterogeneous and recyclable catalyst. Under balloon pressure of CO, 0.6?mol% Pd/C is sufficient for moderate yields of flavones for the carbonylation of aryl iodides under phosphine-free conditions and aryl bromides in the presence of phosphine ligand. The catalyst is easily separable and shows significant recyclability. Moreover, the reaction mechanism was discussed, and a possible mechanism that contains two different cyclisation pathways was proposed.
- Lei, Yizhu,Li, Zhi,Wan, Yali,Zhou, Xiao-Yu,Li, Guangxing,Shi, Kaiyi
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- An Efficient One-Pot Synthesis and Anticancer Activity of 4'-Substituted Flavonoids
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A number of 4'-substituted (R = H, Me, Cl, F) flavone derivatives is synthesized from 2-hydroxyacetophenones using the modified Baker–Venkataraman reaction. Compound [3-(4-fluorobenzoyl)-5- hydroxy-4'-fluoroflavone] was synthesized for the first time with the yield of 12%. Antiproliferative assays indicate that the synthesized flavones with F substituent at the 4' position demonstrate higher activity than the other flavone derivatives, particularly against HeLa and MCF-7 with the IC50 9.5 and 2.7 μM, respectively.
- Wang,Liu,Zhang
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p. 1036 - 1041
(2018/07/06)
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- Synthesis of novel fused chromone-pyrimidine hybrids and 2,4,5-trisubstituted pyrimidine derivatives via ANRORC rearrangement
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A facile and versatile procedure for the synthesis of functionalized novel 2,5-diphenyl-5H-chromeno[4,3-d]pyrimidin-5-ol and (2,4-diphenylpyrimidin-5-yl) (2-hydroxyphenyl) methanone has been described. The key step in the synthesis involves the ANRORC rea
- Sambaiah,Raghavulu,Shiva Kumar,Yennam, Satyanarayana,Behera, Manoranjan
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supporting information
p. 10020 - 10026
(2017/09/18)
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- New gas-phase domino processes leading to benzopyranones and benzofurans
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A new domino approach to flavones by gas phase pyrolysis of β,γ-dioxophosphonium ylides containing a 2-methoxyphenyl group is frustrated by unexpected and novel decarbonylation of the intermediate flavon-3-yl radical leading to 2-phenylbenzofuran. Alternative approaches based on dioxolane protection of one carbonyl, or selective elimination in β,β′-dioxo or β-oxo-β′-thioxo ylides were not successful, but pyrolysis of a β-oxo-β′-phenylimino ylide did give the required domino reaction leading to a protected benzopyranone in moderate yield.
- Aitken, R. Alan,Chang, Da
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p. 164 - 184
(2017/03/11)
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- One-Pot Synthesis of Benzopyran-4-ones with Cancer Preventive and Therapeutic Potential
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A one-pot synthesis of novel benzopyran-4-ones is described. In a tandem reaction, organobase-catalysed Michael addition of R1COCH2COR2 on chromone-3-carboxylic acid led to decarboxylation and pyran-4-one ring opening of the latter. This was followed by chromone-and/or chromanone ring closure of the resulting Michael adducts when R1 is an ortho-hydroxyaryl group. Antioxidant testing of 14 derivatives identified strong antiradical properties of chromanones 3o-r (2.1-3.1 μmol Trolox equiv./μmol compound in the DPPH assay). Chromanones 3p and 3r and 2-styrylchromone 3k were also most potent in inducing the cytoprotective Keap1-Nrf2 signalling pathway in a reporter gene assay (fivefold induction at concentrations 3 μM). Of the seven compounds evaluated for antiproliferative activities, 3k and 3r were the most active, inhibiting leukaemia K562 cell proliferation by 50 % after 72 h at concentrations of 4.5 and 7.9 μM, whereas normal peripheral blood mononuclear cells were not affected. Chromanones 3p and 3r and 2-styrylchromones 3k potently activate the Nrf2 response in the AREc32 cell line at low micromolar concentrations (C5 3 μM). Compounds 3k and 3r are also the most active in inhibiting cell proliferation by 50 % after 72 h incubation at concentrations of 4.5 and 7.7 μM, whereas normal peripheral blood mononuclear cells were not affected.
- Talhi, Oualid,Brodziak-Jarosz, Lidia,Panning, Jana,Orlikova, Barbora,Zwergel, Clemens,Tzanova, Tzvetomira,Philippot, Stéphanie,Pinto, Diana C. G. A.,Paz, Filipe A. Almeida,Gerhaüser, Clarissa,Dick, Tobias P.,Jacob, Claus,Diederich, Marc,Bagrel, Denyse,Kirsch, Gilbert,Silva, Artur M. S.
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p. 965 - 975
(2016/03/01)
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- Decoupling Activation of Heme Biosynthesis from Anaerobic Toxicity in a Molecule Active in Staphylococcus aureus
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Small molecules active in the pathogenic bacterium Staphylococcus aureus are valuable tools for the study of its basic biology and pathogenesis, and many molecules may provide leads for novel therapeutics. We have previously reported a small molecule, 1, which activates endogenous heme biosynthesis in S. aureus, leading to an accumulation of intracellular heme. In addition to this novel activity, 1 also exhibits toxicity towards S. aureus growing under fermentative conditions. To determine if these activities are linked and establish what features of the molecule are required for activity, we synthesized a library of analogs around the structure of 1 and screened them for activation of heme biosynthesis and anaerobic toxicity to investigate structure-activity relationships. The results of this analysis suggest that these activities are not linked. Furthermore, we have identified the structural features that promote each activity and have established two classes of molecules: activators of heme biosynthesis and inhibitors of anaerobic growth. These molecules will serve as useful probes for their respective activities without concern for the off target effects of the parent compound.
- Dutter, Brendan F.,Mike, Laura A.,Reid, Paul R.,Chong, Katherine M.,Ramos-Hunter, Susan J.,Skaar, Eric P.,Sulikowski, Gary A.
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p. 1354 - 1361
(2016/06/09)
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- Novel synthetic method for flavonoid compound
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A novel synthetic method for flavonoid compounds comprises the following steps: 1) fully mixing 21.4 g (0.21 mol) of acetic anhydride and 18.8 g (0.2 ml) of phenol; 2) placing the mixture in ice water bath, adding concentrated sulfuric acid by three drops to the mixture, shaking the mixture, performing fractionation to obtain acetic acid, and collecting the fraction at 194-196 DEG C to obtain liquid phenyl acetate which is colorless and transparent; 3) adding 1-o-hydroxyphenyl-3-phenyl-1,3-propanedione and 20 ml of glacial acetic acid into a 100 ml round-bottom flask, uniformly mixing the components, adding 0.8 ml of concentrated sulfuric acid to interior of the mixture, mounting a reflux condensing tube and heating the mixture for 1 h in boiled water; 4) weighing 100 g of crush ice by a beaker and pouring the mixture into the beaker with continuous stirring until ice is dissolved completely; and 5) performing suction filtration to solid and washing the solid in water continuously until acidity is eliminated, and finally weighing the dried product to obtain the flavonoid compound 2-phenyl benzopyrone.
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Paragraph 0018
(2016/11/28)
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- Mild and efficient organocatalytic method for the synthesis of flavones
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A convenient and efficient organocatalytic procedure for the selective cyclization of 1,3-diketones to give aromatic substituted 4H-chromen-4-ones under mild reaction conditions using N-triflyl phosphoramide is described. Application of the described conditions is presented in a formal synthesis of (S)-flavanone.
- Stanek, Filip,Stodulski, Maciej
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supporting information
p. 3841 - 3843
(2016/08/02)
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- Synthesis and anti-trypanosoma cruzi activity of diaryldiazepines
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Chagas disease is a so-called "neglected disease" and endemic to Latin America. Nifurtimox and benznidazole are drugs that have considerable efficacy in the treatment of the acute phase of the disease but cause many significant side effects. Furthermore, in the Chronic Phase its efficiency is reduced and their therapeutic effectiveness is dependent on the type of T. cruzi strain. For this reason, the present work aims to drive basic research towards the discovery of new chemical entities to treat Chagas disease. Differently substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines were synthesized by cyclocondensation of substituted flavones with ethylenediamine and tested as anti-Trypanosoma cruzi candidates. Epimastigotes of the Y strain from T. cruzi were used in this study and the number of parasites was determined in a Neubauer chamber. The most potent diaryldiazepine that reduced epimastigote proliferation exhibited an IC50 value of 0.25 μM, which is significantly more active than benznidazole.
- Menezes, Jlio Csar L.,Vaz, Luana Beatriz A.,De Vieira, Paula Melo Abreu,Fonseca, Ktia Da Silva,Carneiro, Cludia Martins,Taylor, Jason G.
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- Synthesis and discovery of (I-3,II-3)-biacacetin as a novel non-zinc binding inhibitor of MMP-2 and MMP-9
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Eleven biflavones (7a-b and 9a-i) were synthesised by a simple and efficient protocol and screened for MMP-2 and MMP-9 inhibitory activities. Amongst them, a natural product-like analog, (I-3,II-3)-biacacetin (9h) was found to be the most potent inhibitor
- Nanjan, Pandurangan,Nambiar, Jyotsna,Nair, Bipin G.,Banerji, Asoke
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p. 3781 - 3787
(2015/07/27)
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- Discovery of 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol- 9(2H)-one as a phosphodiesterase-5 inhibitor and its complex crystal structure
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Phosphodiesterase-5 (PDE5) inhibitors have been approved for the treatment of erectile dysfunction and pulmonary hypertension, but enthusiasm on discovery of PDE5 inhibitors continues for their potential new applications. Reported here is discovery of a series of new PDE5 inhibitors by structure-based design, molecular docking, chemical synthesis, and enzymatic characterization. The best compound, 3-(4-hydroxybenzyl)-1-(thiophen-2-yl)chromeno[2,3-c]pyrrol-9(2H)-one (57), has an IC50 of 17 nM against the PDE5 catalytic domain and good selectivity over other PDE families. The crystal structure of the PDE5 catalytic domain in complex with 57 was determined at 2 A resolution and showed that 57 occupies the same pocket as other PDE5 inhibitors, but has a different binding pattern in detail. On the basis of the binding pattern of 57, a novel scaffold can be proposed as a candidate of PDE inhibitors.
- Shang, Na-Na,Shao, Yong-Xian,Cai, Ying-Hong,Guan, Matthew,Huang, Manna,Cui, Wenjun,He, Lin,Yu, Yan-Jun,Huang, Lei,Li, Zhe,Bu, Xian-Zhang,Ke, Hengming,Luo, Hai-Bin
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- Synthesis of B-ring substituted flavones and evaluation of their antitumor and antioxidant activities
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A series of flavones, substituted at the ring B, were synthesized using either Claisen-Schimdt Condensation or Baker-Venkataraman rearrangement. The synthesized compounds were tested for in vitro cytotoxic activity by sulforhodamine B assay against three cell lines of different origin, viz. HepG2, MCF-7, and MOLT-4. The compounds were also tested for a possible antioxidant activity by determination of inhibition of lipid peroxidation. Quercetin was taken as a standard for antioxidant activity. Compound 1c showed the highest cytotoxic activity against MCF-7 (GI50 0.1 μM) and MOLT-4 (GI50 0.1 μM) cell lines and was comparable to adriamycin, the standard used. Compounds 1b, 1g, and 1h also showed promising activity against MCF-7 and MOLT-4 cell lines. In the absence of a hydroxyl group, one or more methoxy groups present on the B-ring (compounds 1c-1e) were major determinants of inhibition of lipid peroxidation.
- Joshi, Akshada J.,Gadhwal, Manoj K.,Joshi, Urmila J.,D'Mello, Priscilla,Sinha, Ragini,Govil, Girjesh
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p. 4293 - 4299
(2013/09/02)
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- An efficient synthesis of 3-bromoflavones under solvent free conditions using grinding technique
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Selective bromination of 1-(2-hydroxyphenyl)-3-phenylpropane- 1,3-diones has been carried out with ammonium bromide and ammonium persulphate at room temperature using grinding technique under solvent free conditions to give 2-bromo derivatives which on cyclodehydration with p-toluenesulphonic acid under grinding conditions give 3-bromoflavones. Also, flavones on bromination using above mentioned conditions give 3-bromoflavones directly.
- Jakhar, Komal,Makrandi
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body text
p. 770 - 773
(2012/06/30)
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- Synthesis of multi-functionalized chromeno[2, 3-c]pyrrol-9(2H)-ones: Investigation and application of Baker-Venkataraman rearrangement involved reactions catalyzed by 4-(Dimethylamino)pyridine
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An efficient one-pot synthesis of multi-functionalized chromeno[2, 3-c]pyrrol-9(2H)-ones from 1, 3-diaryl-1, 3-diket-ones and amino acids is described. The synthesis is based on the 4-(dimethylamino)pyridine-catalyzed Baker-Venkatara-man rearrangement and
- Yu, Yanjun,Hu, Yun,Shao, Weiyan,Huang, Jianing,Zuo, Yinglin,Huo, Yingpeng,An, Linkun,Du, Jun,Bu, Xianzhang
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experimental part
p. 4551 - 4563
(2011/10/03)
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- Synthesis and properties of photosensitive compounds based on bromine-containing 3-acyl-2-furylchromones
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Methods have been developed for the synthesis of new photosensitive compounds based on the reaction of N,S,O-nucleophiles with 3-acyl-2-(5-bromofur- 2-yl)chromones and 3-acyl-2-(5-bromomethylfur-2-yl)chromones. The relationship between the spectral proper
- Levchenko,Barachevski,Yarovenko,Krayushkin,Semenova,Kobeleva,Valova,Shmelin
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scheme or table
p. 155 - 165
(2011/12/21)
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- Facile synthesis of new substituted 3-aryl/heteroarylflavones by Suzuki-Miyaura coupling of 3-bromoflavone with substituted aryu heteroarylboronic acids
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Flavones 7a-k having aryl and heteroaryl substituents at 3-position were synthesized in a Panasonic microwave-oven by Suzuki-Miyaura cross coupling reaction using 3-bromoflavone 5 and substituted aryl and heteroaryl boronic acids 6a-k with tetrakistriphenylphospine-palladium |(C6H 6)3P]4Pd as catalyst and N,N-dimethylformamide (DMF)+ H2O (9:4) as solvent, and aq.Na2CO3(2N) as base.
- Joshi, Vidya,Hatim, Jaywant Govind
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p. 111 - 116
(2013/09/24)
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- Experimental validation and docking studies of flavone derivatives on aldose reductase involved in diabetic retinopathy, neuropathy, and nephropathy
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The enzyme aldoreductase which plays an important role in pathogenesis of diabetic retinopathy, neuropathy, and nephropathy was purified from bovine lens, and its inhibitory activity was studied with the synthesized flavone derivatives 1-(2-hydroxyphenyl)ethanone as the starting material. Experimental study revealed that 2-chloroflavone shows less inhibitory activity of 60-70% than other flavones used in the study. To validate experimental results computationally, docking studies of new flavone derivatives synthesized were performed with the enzyme aldose reductase, and the results indicate that 3-iodo, 4-methyl, 5-chloroflavone and 2-chloroflavone bind with higher and lesser affinities. Docking studies with site directed mutagenesis of Val47Ile, Tyr48His, Pro121Phe, Trp219Tyr, Cys298Ala, Leu300Pro, Ser302Arg, and Cys303Asp of the enzyme altered the inhibition activity of aldose reductase. The regression value (R2) of 0.81 between the docking scores of the known inhibitors and the experimental logIC50 indicates the reliability of the docking studies. Biological activity and carcinogenic properties predict that 3-iodo, 4-methyl, 5-chloroflavone is the best flavone inhibitor against aldose reductase. Springer Science+Business Media, LLC 2010.
- Sekhar, Pagadala Nataraj,Kishor, P.B. Kavi,Zubaidha,Hashmi,Kadam,Anandareddy, Lakkireddy,Maeyer, Marc De,Kumar, K. Praveen,Bhaskar, B. Vijaya,Munichandrababu,Jayasree,Narayana,Gyananath
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experimental part
p. 930 - 945
(2012/06/30)
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- An efficient one-pot synthesis of flavones
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Flavones were prepared using a one-pot procedure starting from the corresponding 2′-hydroxyacetophenones. The latter were treated with 3 equiv of aroyl chloride in wet K2CO3/acetone (1% w/w water) to afford a good yield of flavone and a smaller amount of 3-aroylflavone. Evidence was obtained that the reaction proceeds via a triketone intermediate. When the reactants were heated in 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and pyridine, the 3-aroylflavone was obtained exclusively. Use of a stoichiometric amount of aroyl chloride afforded only the corresponding flavone.
- Chee, Chin Fei,Buckle, Michael J.C.,Rahman, Noorsaadah Abd.
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scheme or table
p. 3120 - 3123
(2011/06/26)
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- Synthesis, spectroscopic characterisation and X-ray analysis of regioisomeric 1,3,5-trisubstituted pyrazoles
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A new series of regioisomeric 1,3,5-trisubstituted pyrazoles 7-9(a,b) have been synthesized by the reaction of β-diketones (4-6) with methyl hydrazine in ethanol. All the compounds are characterised by the FT-IR, 1H, 13C NMR and mass spectrometry. The crystal structure of compounds 7a, 7b and minor isomer 8b have been determined by X-ray single crystal analysis which showed either of the substituted groups attached to pyrazole ring are essentially non-planar to the central pyrazole ring. Addition of trace amounts of acetic acid during the synthesis of compound 8 resulted in an unexpected compound 10 which is characterised by the X-ray single crystal analysis and is essentially planar. However, crystal structure of 10 is already reported. All structures are further stabilized by the classic and non-classic inter- and intramolecular hydrogen bonding.
- Yunus, Uzma,Kauser, Rukhsana,Bhatti, Moazzam H.,Zia-Ul-Haq, Muhammad,Wong, Wai-Yeung
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scheme or table
p. 173 - 180
(2011/07/31)
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- Synthesis and reactivity of 1-aryl-9h-thieno[3,4-b]chromon-9-ones
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Methods were developed for the synthesis of 1-aryl-9H-thieno[3,4-b]chromon- 9-ones based on the reaction of bromo and dibromo derivatives of 2-methyl-4H-chromon-4-one with thioacetamide in DMF. The thienochromones were modified and their fluorescence prop
- Krayushkin, Mikhail M.,Levchenko, Konstantin S.,Yarovenko, Vladimir N.,Christoforova, Ludmila V.,Barachevsky, Valery A.,Puankov, Yury A.,Valova, Tatyana M.,Kobeleva, Olga I.,Lyssenko
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experimental part
p. 2267 - 2277
(2011/04/23)
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- New synthesis of 3-bromoflavones via bromination of 1-(2-hydroxyphenyl)-3- arylpropane-1,3-dione by CuBr2, and conversion into 3-aminoflavones
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A new synthesis of 3-bromoflavones from 1-(2-hydroxyphenyl)-3-arylpropane- 1,3-dione using CuBr2 is described. The usefulness of 3-bromoflavone as a precursor of 3-aminoflavone is also described. Copyright
- Miyake, Hideyoshi,Nishino, Shouko,Nishimura, Akinori,Sasaki, Mitsura
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p. 522 - 523
(2008/02/10)
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- Fast synthesis of some flavones under microwave irradiation
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Reactions under microwave irradiation occur under solvent free conditions. Such reactions occur in much shorter time than the usual ones. Fast synthesis of flavone from o-hydroxyacetophenone has been achieved in three steps under microwave irradiation.
- Mumtazuddin
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p. 835 - 837
(2007/10/03)
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- Synthesis and antibacterial activity of substituted flavones, 4-thioflavones and 4-iminoflavones
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Synthesis of flavones, 4-thioflavones and 4-iminoflavones was carried out with the substitution of variable halogens, methyl, methoxy and nitro groups in the A, B and AB rings of the respective compounds and we also report here their antibacterial activity. Most of the synthesized compounds were found to be active against Escherichia coli, Bacillus subtilis, Shigella flexnari, Salmonella aureus, Salmonella typhi and Pseudomonas aeruginosa. Activity of 4-thioflavones and 4-iminoflavones was found to be higher than that of their corresponding flavone analogues. Investigated compounds having substituents like F, OMe and NO2 at 4′-position in ring-B exhibited enhanced activity and the presence of electronegative groups in the studied compounds showed a direct relationship to the antibacterial activity.
- Ullah Mughal, Ehsan,Ayaz, Muhammad,Hussain, Zakir,Hasan, Aurangzeb,Sadiq, Amina,Riaz, Muhammad,Malik, Abdul,Hussain, Samreen,Choudhary, M. Iqbal
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p. 4704 - 4711
(2007/10/03)
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- One pot synthesis of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones by modified Baker-Venkataraman transformation using microwave irradiation
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Reaction of 2-hydroxyacetophenones with aromatic acid anhydrides in the presence of anhydrous barium hydroxide in dimethyl sulfoxide using microwave irradiation gives 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones directly in a single pot reaction in high yields.
- Lamba,Kumar, Suresh,Makrandi
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p. 133 - 134
(2007/10/03)
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- Synthesis of 3-alkenyl-2-arylchromones and 2,3-dialkenylchromones via acid-catalysed retro-Michael ring opening of 3-acylchroman-4-ones
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3-Acylchromones and 3-acylflavones, readily available by acylation of 2′-hydroxydibenzoylmethane with acid anhydrides in the presence of base, undergo efficient conjugate reduction with NaBH4 in pyridine to give the corresponding chroman-4-ones/flavanones in high yields. The reduction is both regio- and chemoselective. Treatment of the chroman-4-ones with MeSO 3H generates the 3-alkenyl-2-arylchromones by a dehydrative rearrangement initiated by retro-Michael cleavage of the pyranone ring. This reduction-rearrangement sequence can be extended to 2-alkyl-3-alkenoylchromones to generate 3-alkenyl-2-styrylchromones, the first examples of 2,3-dialkenylchromones.
- Clarke, David S.,Gabbutt, Christopher D.,Hepworth, John D.,Heron, B. Mark
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p. 5515 - 5519
(2007/10/03)
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- Photochemical synthesis of 2,2′-biflavanones from flavone
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Photolysis of flavone (4) with the electron-donating amines including triethylamine or 2-(N,N-dimethylamino)ethanol in acetonitrile, benzene or methylene dichloride can easily afford two hydrodimers of 2,27prime;-bi- flavanone(racemate) (5a) and 2,2′-biflavanone(meso) (5b) and one reductive product of flavanone (6). Their yields were dependent on the molar ratios of substrate to amine, the kinds of amines, the solvents used and the irradiation sources. Higher yields were afforded 2,27prime;-biflavanone(racemate) (5a), 2,27prime;-biflavanone(meso) (5b) and flavanone (6) (30.0%, 20.9% and 15.8%, respectively) in the reaction condition of 1/2 molar ratio of flavone (4) to triethylamine in acetontrile with fourteen hours of irradiation.
- Chen, Arh-Hwang,Kuo, Wei-Bao,Chen, Chia-Wen
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p. 123 - 127
(2007/10/03)
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- Benzopyrans. Part 41.1 Reactions of 2-(2-dimethylaminovinyl)-lbenzopyran-4-ones with various dienophiles
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Dienamine 1 with W-phenylmaleimide and chromenone 14 as well as 15 produces, through initial [4 + 2]cycloaddition, xanthenones 10 and 18, respectively. Initial Michael addition of 1 to chromenones 14 and 16, and dimethyl acetylenedicarboxylate (DMAD), triggers the formation of xanthenone 19, 4-azaxanthenone 26 and substituted fumarate 49, respectively. Initial [2 + 2]cycloadducts of dienamines 1-3 with electrophilic acetylenes always undergo further transformations. Thus, 1 with DMAD, dibenzoylacetylene and ethyl propiolate (EP) ultimately gives xanthenones 33, 34 and 37, respectively, the latter being admixed with flavone 43. Enamine 2, cyclisable to xanthenone 11, gives 33 and 35 with DMAD, and 37 and 44 with EP. Reaction of 3 with DMAD affords 36 exclusively. The Royal Society of Chemistry 1999.
- Ghosh, Chandra Kanta,Bhattacharyya, Samita,Ghosh, Chandreyi,Patra, Amarendra
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p. 3005 - 3013
(2007/10/03)
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- Synthesis of halogenated/nitrated flavone derivatives and evaluation of their affinity for the central benzodiazepine receptor
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A series of halogenated/nitrated flavone compounds were synthesized. Some of the products were found to be potent central benzodiazepine receptor (BDZ-R) ligands. The structure-activity relationships (SAR) analysis of the new synthetic compounds, together with that of others already described, indicates that substitutions at position 6 or 6 and 3' in the flavone nucleus are the only ones that give rise to high affinity BDZ-R ligands.
- Marder, Mariel,Zinczuk, Juan,Colombo, Maria I.,Wasowski, Cristina,Viola, Haydee,Wolfman, Claudia,Medina, Jorge H.,Ruveda, Edmundo A.,Paladini, Alejandro C.
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p. 2003 - 2008
(2007/10/03)
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- New synthesis of 1,3-diarylpropane-1,3-diones
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1,3-Diarylpropane-1,3-diones have been synthesized by (i) UV irradiation and thermal rearrangement of o-aroyloxyacetophenones and (ii) microwave irradiation of aroyl chlorides and o-hydroyacetophenones.
- Bansal,Singh,Khanna
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p. 586 - 587
(2007/10/03)
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- A new metal complex promoted system for highly selective synthesis of 4H-chromen-4-ones (chromones)
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Co(III)(salpr)(OH), a six coordinate cobalt Schiff base complex, promotes the highly selective conversion of 1-(o-hydroxyaryl)-1,3-diketones to 4H-chromen-4-ones under neutral conditions.
- Nishinaga,Ando,Maruyama,Mashino
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p. 839 - 841
(2007/10/02)
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- A practical synthesis of flavones from methyl salicylate
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A facile synthetic method has been developed for the conversion of methyl salicylate (5) into flavones 1a-i in high yields. Compound 5 on treatment with t-butyldimethylsilyl chloride (6) gave the O-silyl protected ester 7. Condensation of this ester 7 with the lithium anion generated from acetophenones 3a-i yielded the 1.3-diarylpropane-1,3-diones 8a-i, which on treatment with glacial acetic acid containing 0.5% H2SO4 for 3 h at 95-100°C provided the desired flavones 1a-i in 83-94% yields.
- Nagarathnam, Dhanapalan,Cushman, Mark
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p. 5071 - 5076
(2007/10/02)
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- Structural Studies on Bio-active Compounds. Part 12. Tautomerism and Conformation of Aryl-substituted 1-(2-Hydroxyphenyl)-3-phenylpropane-1,3-diones in the Solid Phase and in Solution
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The tautomerism of a series of aryl-substituted 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones has been studied in deuteriochloroform solution by 1H n.m.r. techniques and, in the case of 1-(2-hydroxy-4-methoxyphenyl)-3-phenylpropane-1,3-dione and 1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylpropane-1,3-dione, in the solid state by X-ray crystallography.Of these compounds, most exist between 80 and 95percent in the enolised form in solution and 1-(2-hydroxy-4-methoxyphenyl)-3-phenylpropane-1,3-dione adopts this tautomer in the crystal.However, 1-(2-hydroxy-4,6-dimethoxyphenyl)-3-phenylpropane-1,3-dione is present as the diketone in the solid phase and enolises very slowly in solution. 1-(6-Benzoyloxy-2-hydroxyphenyl)-3-hydroxy-3-phenylprop-2-en-1-one is shown by 1H n.m.r. spectroscopy possibly to adopt a 'coiled' conformation in solution in deuteriochloroform.
- Cunningham, Bernadette D. M.,Lowe, Philip R.,Threadgill, Michael D.
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p. 1275 - 1284
(2007/10/02)
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- PHOTOACTIVABLE FLUOROPHORENES. 2. SYNTHESIS AND PHOTOACTIVATION OF FUNCTIONALIZED 3-AROYL-2-(2-FURYL)-CHROMONES
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The synthesis and photochemistry of functionalized 3-aroyl-2-(2-furyl)-chromones 1 which are photoactivable fluorophores are described.Irradiation converts the non-fluorescent furyl chromones to highly fluorescent 1-arylfuro chromones 3.Functionality has been incorporated to permit covalent attachment, impart aqueous solubility and to maximize the fluorescence of the ultimate 1-arylfurochromone fluorophore.An efficient synthetic pathway to the furyl chromones via an intramolecular Dieckman cyclization also is described.
- Cummings, Richard T.,DiZio, James P.,Krafft, Grant A.
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- ALKALINE DEGRADATION OF PARENT CHROMONOID COMPOUNDS (CHROMONE, FLAVONE, ISOFLAVONE)
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Ring-opening and degradation processes of parent flavonoid compounds under alkaline conditions have been studied by means of thin-layer chromatography.The direction of the splitting has been found dependent on the OH(1-) ion concentration.In the case of isoflavone salicylic acid was present in the reaction mixture, indicating a novel type of degradation of isoflavonoids.
- Zsuga, Miklos,Kiss, Aniko
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p. 485 - 490
(2007/10/02)
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- Reactions of Carbonyl Compounds in Basic Solutions. Part 11. The Baker-Venkataraman Rearrangement
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The detailed mechanism of the Baker-Venkataraman rearrangement has been studied.The kinetics of the rearrangement of a series of 2-acetylphenyl 3- or 4-substituted benzoates and acetylnaphthyl benzoates catalysed by a basic 'non-nucleophilic' buffer in dimethyl sulphoxide have been measured.Studies of substituent effects, kinetic isotope effects, and acidity function correlations indicate a pathway involving pre-equilibrium formation of the carbanion, followed by rate-determining intramolecular nucleophilic attack.The methanolysis of the 2-acetylphenyl benzoates catalysed by methoxide in methanolic dimethyl sulphoxide has been similary investigated.In this case the pathway appears to involve neighbouring group participation by the ketonic carbonyl group.
- Bowden, Keith,Chehel-Amiran, Mohsen
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p. 2039 - 2044
(2007/10/02)
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