Algar Flynn Oyamada Research Articles

The three-component photoinitiating systems based on flavonol sulfonate and application in 3D printing

Three-dimensional (3D) printed photocurable shape-shifting polymers based on a three-component photoinitiated system (PIS) (flavonol sulfonate/triethanolamine/iodonium salt) were studied. The flavonol sulfonate (3HF–F) with charge transfer ability and long-wavelength absorption was designed and prepared using the Algar–Flynn–Oyamada method which is an important component of the oxidation–reduction PIS initiating the polymerization of polyethylene glycol (600) diacrylate (PEGDA) under 405 nm LED. For light absorption (active absorber) and electron/proton transfer, the three-component PIS has high-function conversion, and short induction period during the photopolymerization of PEGDA. As the same time, 3HF–F could also undergo passive absorption to obtain high-resolution DLP 3D-printed polymers. The printed polymers could be reversibly modified by means of hydrophilic and thermal responses caused by the stimuli-responsiveness of the polymer chains to activate the shifting of shape.

Flavonol dyes with different substituents in photopolymerization

To further expand the applications of flavonol dyes (3HFs) in photopolymerization, six flavonol dyes with different substituents were prepared by using the Algar–Flynn–Oyamada method. The steady-state photolysis and fluorescence quenching of 3HFs under the 385 nm LED light source showed that the proton transfer reaction preceded the charge transfer reaction between 3HFs and triethanolamine (TEOA) or iodonium salts (ONI), and groups with different electron properties could affect the photochemistry of 3HFs. The influence of substituents on the free radical polymerization efficiencies of 3HFs/TEOA and 3HFs/ONI was evaluated. Results showed that charge transfer occurred in the oxidation or reduction processes between 3HFs and TEOA or ONI. The possible mechanism was speculated, and the thermal feasibility of charge transfer between 3HFs and TEOA or ONI was calculated on the basis of the free energy changes of photoinduced electron transfer.

Synthesis, biological evaluation, and molecular docking of dihydroflavonol derivatives as anti-inflammatory agents

A series of dihydroflavonol derivatives (4a–4l) were synthesized from chalcones via classical Algar–Flynn–Oyamada (AFO) reaction and characterized on the basis of spectroscopic analyses. All synthesized compounds were evaluated for their inhibitory activity against the pro-inflammatory-inducible TNF-alpha, IL-1beta, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell lines and showed various efficiency. Furthermore, compounds 4d and 4k were selected to examine their in vivo anti-inflammatory activity by using two classical models. Herein compound 4k showed maximum anti-inflammatory activity of 32.98% inhibition in mice ear-swelling model and 40.06% inhibition at the 2 h intervals in rat paw edema model in comparison to the two references: aspirin and meloxicam. Similar effect was observed at a lower dose. In addition, the compound 4k was docked against cyclooxygenases-2 to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory activity.

SYNTHESIS, IN VITRO ANTIOXIDANT AND ANTIMICROBIAL EVALUATION OF 3-HYDROXY CHROMONE DERIVATIVES

Objective: The objective of the present study was to synthesize a series of 3-hydroxychromone derivatives and to evaluate its in vitro antioxidant and antimicrobial activities.Methods: 3-hydroxy chromones were synthesized using an algar flynn oyamada method which includes oxidative cyclization of 2-hydroxy chalcones in basic solution by hydrogen peroxide. 2-hydroxy chalcones were synthesized by Claisen-Schmidt condensation of substituted 2-hydroxy acetophenones with substituted aromatic aldehydes using polyethylene glycol-400 as a recyclable solvent. The synthesized compounds were evaluated for in vitro antioxidant activity by 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. In addition, these compounds were also screened for in vitro antibacterial and antifungal activity by agar cup method and Poison plate method, respectively.Results: The structures of the synthesized compounds were characterized by infrared, 1H nuclear magnetic resonance and mass spectroscopy. The antioxidant activity data revealed that all the synthesized derivatives exhibited good activity due to the presence of phenolic hydroxyl group, 4-oxo group and 2,3-double bond. Further, the activity increased with the introduction of a more phenolic hydroxyl group and adjacent methoxy group in the structure. The antimicrobial activity data showed that the compounds possess better antibacterial and antifungal activity which is attributed to the presence of phenolic hydroxyl group and 4-oxo group in the structure.Conclusions: The use of inexpensive, eco-friendly and readily available reagents, easy work-up and high purity of products makes the procedure a convenient and robust method for the synthesis of title compounds. The presence of phenolic hydroxyl group, 4-oxo group, and 2,3-double bond in the structure is responsible for their good antioxidant and antimicrobial activities.

One-pot synthesis of spirochromanone-based 3-hydroxy-4H-chromen-4-ones by a modified Algar–Flynn–Oyamada reaction and evaluation of their antimicrobial activity

A novel series of spirochromone-flavonol derivatives were synthesized starting from a monospirochromone moiety using NaOH and H 2 O 2 by a modified Algar–Flynn–Oyamada reaction. In this method, the title compounds were synthesized in good yields without isolating chalcones. The structures of the synthesized compounds have been established on the basis of physical and spectral data (IR, 1 H, 13 C NMR, and mass spectra). All the newly synthesized compounds were screened for in vitro antimicrobial activity. All the compounds were shown moderate to good antimicrobial activity. Normal 0 false false false 300 A novel series of spirochromone-flavonol derivatives were synthesized starting from a monospirochromone moiety using NaOH and H 2 O 2 by a modified Algar–Flynn–Oyamada reaction. In this method, the title compounds were synthesized in good yields without isolating chalcones. The structures of the synthesized compounds have been established on the basis of physical and spectral data (IR, 1 H, 13 C NMR, and mass spectra). All the newly synthesized compounds were screened for in vitro antimicrobial activity. All the compounds were shown moderate to good antimicrobial activity. Normal 0 false false false

Synthesis of 5-subsituted flavonols via the Algar-Flynn-Oyamada (AFO) reaction: The mechanistic implication

Herein, we report a synthetic method with improved selectivity for 5-substituted flavonols via the Algar-Flynn-Oyamada reaction (AFO), by using of sodium carbonate/hydrogen peroxide A series of 5-substituted flavonols was obtained with moderate to high yields. The mechanism of the AFO reaction was elucidated. LCMS analysis and in situ 1H NMR analysis indicated that the epoxide was involved in the transformation from chalcone to flavonol and/or aurone under alkaline base/peroxide conditions.

Limitation of Algar–Flynn–Oyamada reaction using methoxy substituted chalcones as reactants and evaluation of the newly transformed aurones for their biological activities

The study describes newly synthesized 7-(1-Benzyl-1,2,3,6-tetrahydro-pyridin-4-yl)-4,6-dimethoxy aurones (SJA 1–14) obtained as final compounds by the oxidative cyclisation of chalcone intermediates in the presence of alkaline hydrogen peroxide catalyst. Their structures were confirmed by spectral analysis and were further evaluated for their in vitro antioxidant and anticancer activities. To support their physicochemical characteristics, distribution coefficients (log D 7.4) and oxidation potentials (Epa) were determined. Among the test compounds, SJA 8 and SJA 11 were found cytotoxic to MCF-7, T47D and MDA MB-231 in the IC50 range of 16.63 ± 1.00–43.93 ± 2.09 µM when compared to doxorubicin in the IC50 range of 0.23 ± 0.03–8.32 ± 0.46 µM. Further studies performed with SJA 8 and SJA 11 on MCF-7 showed that they significantly increased the apoptotic index as compared to the control and displayed a G 0/G 1 phase arrest of the cell cycle. It was observed that synthesised aurones possessing para substitution on ring B showed cytotoxic activity and possessed log D 7.4 in the range of 2.5–3.2. Conversely, radical scavenging activity of aurones was in the IC50 range of 71.67 ± 0.24 to >1000 µM when compared to ascorbic acid and quercetin in the IC50 range of 15.46 ± 1.30–34.42 ± 0.03 µM. However, their low antioxidant potential was supported by their high Epa values in the range of 0.926–1.008 V when compared to standard antioxidants. Further studies on N-benzyl tetrahydropyridinyl-4,6-dimethoxy substituted aurones would create a platform for understanding their optimum structural features and the extent to which they may be useful as anticancer agents.

A new class of flavonol-based anti-prostate cancer agents: Design, synthesis, and evaluation in cell models

Flavonoids are a large class of polyphenolic compounds ubiquitously distributed in dietary plants with an array of biological activities. Flavonols are a major sub-class of flavonoids featuring a hydroxyl group at C-3. Certain natural flavonols, such as quercetin and fisetin, have been shown by in vitro cell-based and in vivo animal experiments to be potential anti-prostate cancer agents. However, the Achilles’ heel of flavonols as drug candidates is their moderate potency and poor pharmacokinetic profiles. This study aims to explore the substitution effect of 3-OH in flavonols on the in vitro anti-proliferative potency against both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Our first lead flavonol (3′,4′-dimethoxyflavonol), eight 3-O-alkyl-3′,4′-dimethoxyflavonols, and six 3-O-aminoalkyl-3′,4′-dimethoxyflavonols have been synthesized through aldol condensation and the Algar–Flynn–Oyamada (AFO) reaction. The WST-1 cell proliferation assay indicates (i) that all synthesized 3-O-alkyl-3′,4′-dimethoxyflavonols and 3-O-aminoalkyl-3′,4′-dimethoxyflavonols are more potent than the parent 3′,4′-dimethoxyflavonol and the natural flavonol quercetin in suppressing prostate cancer cell proliferation; and (ii) that incorporation of a dibutylamino group to the 3-OH group through a three- to five-carbon linker leads to the optimal derivatives with up to 292-fold enhanced potency as compared with the parent flavonol. Flow cytometry analysis showed that the most potent derivative 22 can activate PC-3 cell cycle arrest at the G2/M phase and induce PC-3 cell apoptosis. No inhibitory ability of 22 up to 50μM concentration was observed against PWR-1E normal human epithelial prostate cells, suggesting its in vitro safety profile. The results indicate that chemical modulation at 3-OH is a vital strategy to optimize flavonols as anti-prostate cancer agents.

Facile synthesis, thermal degradation and effective antimicrobial activities of Cu (II) complexes withbis[3-acetoxy-2-aryl/heteroaryl-4H-chromone

AbstractThis article reports the synthesis of bis [3-acetoxy-2-aryl/heteroaryl-4H-chromone] Cu (II) complexes 6(a–g) in 1:2 stoichiometry ratio of copper acetate and 3-acetoxy-2-aryl/heteroaryl-4H-chromone. While chelating ligands, active functionalized 3-acetoxyflavones (2-aryl/heteroaryl-3-acetoxy-4H-chromones) 5(a–g) are synthesized by Algar–Flynn–Oyamada transformation of chalcones (1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-ones) 4(a–g). The synthesized copper complexes are characterized by the standard techniques such as physical Fourier transform infrared spectroscopy (FT-IR), UV-reflectance spectroscopy, magnetic susceptibility and thermal analysis. Furthermore, antimicrobial activities are investigated using the standard methods. The antifungal activity was tested against Rhizoctonia solani and Candida tropicals, while antibacterial activity was screened against pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa.

New polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones: synthesis and ROS/RNS scavenging activities

New polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones were prepared and assessed as reactive oxygen species (ROS) and reactive nitrogen species (RNS) scavengers. The synthetic strategy involved the preparation of 2′-hydroxychalcones and 2′-hydroxycinnamylidenoacetophenones from base-catalyzed aldol reaction of appropriate 2′-hydroxyacetophenones and benzaldehydes/cinnamaldehydes, followed by an Algar-Flynn-Oyamada (AFO) reaction to give the polyalkoxy(flavon-3-ols and 3-hydroxy-2-styrylchromones). The last step of this synthetic route consisted in the cleavage of the protecting groups affording the expected polyhydroxylated derivatives.The present work consisted in the study of the in vitro scavenging activities of the synthetized compounds against the most physiologically relevant ROS [superoxide radical (O2-), hydrogen peroxide (H2O2), hypochlorous acid (HOCl), singlet oxygen (1O2) and peroxyl radical (ROO)] and RNS [nitric oxide (NO) and peroxynitrite anion (ONOO−)]. Generally, all the tested new polyhydroxylated flavon-3-ols and 3-hydroxy-2-styrylchromones exhibited scavenging effects dependent on the concentration, and with IC50 values found within the micromolar range. This work allowed the establishment of new structure-activity relationships and brought the knowledge about the selective choice of a structure depending on the targeted reactive species.

Microwave-assisted one-pot synthesis of some new flavonols by modified Algar–Flynn–Oyamada reaction and their antimicrobial activity

A new series of 3-hydroxy-2-[1-phenyl-3-(thiophen-2-yl)-1H-pyrazol-4-yl]-4H-chromen-4-ones has been synthesized from substituted 2-hydroxyacetophenones and 1-phenyl-3-(thiophen-2-yl)-1H-pyrazole-4-carbaldehyde using NaOH and H2O2 by modified Algar–Flynn–Oyamada reaction under conventional and microwave irradiation conditions. In this method flavonols are synthesized without isolating chalcones in good yields (80–85%). The structures of the compounds were established on the basis of IR, 1H, 13C NMR and mass spectral and elemental analysis data. The synthesized compounds were screened for their antibacterial and antifungal activities.

Oxovanadium (IV) complexes with O–O donors ligands: efficient synthesis, spectral characterization, antimicrobial activity and thermal degradation

The clinically active functionalized flavonols (2-aryl/heteroaryl-3-acetoxy-4H-chromones) 5(a-g) were synthesized from Algar–Flynn–Oyamada transformation of chalcones (1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-ones) 4(a-g). Furthermore, oxovanadium metal complexes 6(a-g) of ligands 5(a-g) were synthesized and characterized by physical, Fourier transform infrared (FT-IR) spectroscopy, 1H NMR, mass, UV-reflectance spectroscopy, magnetic moment susceptibility, thermal and analytical data. The functionalized flavonol acts as bidentate chelating ligand and coordinate with vanadium metal atom through hydroxyl and carbonyl groups. The complexes have general formula [MOL2] where M = vanadium, O = oxygen and L = ligand. The chelation process reduces the polarity of metal ion by coordinating with ligands, which increase the lipophilic nature of the metals. This lipophilic nature of the metal enhanced its penetration through the lipoid layer of cell membrane of the micro-organism. This constitutes a new group of compounds that can be used as potential metal derived drugs. Therefore, the synthesized compounds were screen for their antifungal activity against A. niger and C. albicans using the cup plate diffusion method, however antibacterial activities screen against pathogenic bacteria such as E. coli, S. aureus, B. subtilis and P. aeruginosa.

Divergent and concise total syntheses of dihydrochalcones and 5-deoxyflavones recently isolated from Tacca species and Mimosa diplotricha

Dihydrochalcones and 5-deoxyflavones are types of compounds possessing various biologically interesting properties. Herein, we report the concise and divergent total syntheses of several naturally occurring dihydrochalcones and 5-deoxyflavones from readily available starting materials. The divergent strategy is based around manipulation of a common chalcone scaffold and features application of Algar–Flynn–Oyamada oxidation and benzoquinone C–H activation methodologies. These are the first reported total syntheses of these biologically interesting compounds and the concise and flexible route should be readily amenable to future analogue generation. Furthermore, this work provides an illustration of the utility of divergent synthesis for the expedient and step-economical preparation of natural product libraries.

Phase Transfer Catalysis Extends The Scope of The Algar–Flynn–Oyamada Synthesis of 3-Hydroxyflavones

The Algar–Flynn–Oyamada reaction is the classical method to synthesize 3-hydroxyflavones from chalcones. Despite its relative simplicity, the reaction has several drawbacks including variable and often low product yields. We have found that phase transfer catalysis improves the yields and expands the scope of the Algar–Flynn–Oyamada reaction of a series of 4-benzyloxy-2-hydroxy chalcones.

Quantum-Chemical Analysis of the Algar–Flynn–Oyamada Reaction Mechanism

This work is devoted to improving the understanding of Algar–Flynn–Oyamada reaction mechanism and the analysis of factors that affect the formation of flavonols. The calculation of thermodynamic parameters for the key reaction steps pointed to a mechanism involving chalcone epoxides as intermediates. A correlation was identified between the nucleophilicity of oxygen atom at position 2' of epoxide anions and the yields of flavonols. An increased charge at the nucleophilic center was shown to reduce the effectiveness of β-cyclization of epoxide anions.

Computational insight of the mechanism of Algar–Flynn–Oyamada (AFO) reaction

The present DFT investigation supports a previous conclusion of Dean et al. that hydroxylation occurs without epoxide intermediate at room temperature due to a strong electrostatic interaction of peroxide ions with π electrons of CC bonds of chalcone, and 3-hydroxyflavone has been found to be the major product. The calculated activation energy difference (ΔG#) of initial enolization followed by hydroxylation or simultaneous cyclization and hydroxylation has been found to be negligible (∼4 kcal mol−1). On the other hand, epoxide formation requires significant activation energy, which is supposed to occur at high temperatures. In addition, if epoxide is formed, the ring opens by an attack of phenolic oxygen, occurring preferentially at α position via a five-member transition state due to a low activation barrier height (19.82 kcal mol−1 in the gas phase and 19.55 kcal mol−1 in ethanol) compared to that of a six-member transition state (44.41 kcal mol−1 at B3LYP in the gas phase and 38.55 kcal mol−1 in ethanol). It is also observed that the solvation study does not affect the main conclusion of the paper. These findings also support the previous observation of Dean et al. Predicted ΔG# in different DFT functionals are consistent, although the total energy is significantly different.

Oxovanadium (IV) complexes of 2-aryl/heteroaryl-3-hydroxy-4H-chromones: synthesis, spectral and thermal degradation studies

The clinically active functionalized flavonols (2-aryl/heteroaryl-3-hydroxy-4H-chromones) (4a-l) have been synthesized from Algar–Flynn–Oyamada transformation of chalcones (1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-ones). Their oxovanadium metal complexes (5a-l) have been prepared and characterized by physical, spectral, thermal and analytical data. The functionalized flavonol acts as bidentate ligand and coordinates with vanadium metal atom through hydroxyl and carbonyl groups. The complexes have general formula [MOL2], where M = vanadium, O = oxygen and L = ligand. The chelation process reduces the polarity of metal ion by coordinating with ligands, which increase the lipophilic nature of the metals. This lipophilic nature of the metal enhanced its penetration through the lipoid layer of cell membrane of the micro-organism. This constitutes a new group of compounds that can be used as potential metal-derived drugs.

Synthesis and biological evaluation of novel 2′,4′,5′-trimethoxyflavonol derivatives as anti-inflammatory and antimicrobial agents

A series of novel 3-hydroxy-2-(2,4,5-trimethoxyphenyl)-4H-chromen-4-one (flavonol) derivatives (2a–u) of biological interest have been prepared via CLAISEN–SCHMIDT condensation followed by ALGAR–FLYNN–OYAMADA reaction and to search for the potent nonsteroidal anti-inflammatory agents from this novel series. All the synthesized compounds have been screened for their in vitro proinflammatory cytokines tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) inhibitory activity along with antimicrobial activity. As many as three compounds viz. 2h, 2l, and 2q from this novel series were found to be potent TNF-α and IL-6 inhibitor (up to 72–81 % TNF-α and 86–92 % IL-6 inhibitory activity) but at 10 μM concentration as compared with the standard dexamethasone (71 % TNF-α and 84 % IL-6 inhibitory activities at 1 μM concentration). While the compounds 2d, 2m, 2n, and 2s were found to be potent antimicrobial agent showing even 2–2.5-fold more potency than that of standard ciprofloxacin and miconazole at the same MIC value of 10 μg/mL.

A One-Pot Synthesis of Aurones from Substituted Acetophenones and Benz­aldehydes: A Concise Synthesis of Aureusidin

A one-pot synthesis of aurones from substituted acetophenone and benzaldehyde has been developed on the basis of an improved Algar–Flynn–Oyamada reaction. By using this method, several aurones were prepared in three steps from commercial starting materials. The usefulness of this one-pot strategy was confirmed by a synthesis of aureusidin, an inhibitor of iodothyronine deiodinase, in 41% overall yield. In comparison with a two-step synthesis of this product from the same substrates, the one-pot strategy was more effective, giving a higher yield and requiring fewer and simpler operations.

Synthesis and antioxygenic activities of seabuckthorn flavone-3-ols and analogs

A practical synthesis of polyhydroxy- and regiospecifically methylated flavone-3-ols which are components of commercial 'seabuckthorn flavone' has been achieved by modified Algar-Flynn-Oyamada method. Antioxidant activities of seabuckthorn extracts, isolated products and a number of flavone-3-ols have been determined. Structure-activity relationships have been discussed. Amongst the compounds tested, gallic acid, which is also present in seabuckthorn, was found to be the most effective antioxidant and radioprotectant.