4-hydroxycoumarin Research Articles

Multicomponent Synthesis and Antimicrobial Activity of Dihydropyran‐bis Coumarins

AbstractA synthetic route for the synthesis of biscoumarin fused with dihydropyran ring via one pot multicomponent reaction using hydroxy coumarins, formyl coumarins and malononitrile as precursors is proposed. A plausible mechanistic pathway for the formation of biscoumarin fused with dihydropyran ring is suggested. The synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR and mass spectral data. Among the synthesized compounds, single crystals of 2‐amino‐5‐oxo‐4‐(2‐oxo‐2H‐chromen‐6‐yl)‐4,5‐dihydropyrano[3, 2‐c]chromene‐3‐carbonitrile were obtained and their crystal parameters were discussed. Further, antimicrobial activities of all the synthesized compounds against microbial pathogens were investigated by broth micro dilution method. Majority of the compounds exhibited promising antimicrobial activities.

Iron-Catalyzed Batch/Continuous Flow C-H Functionalization Module for the Synthesis of Anticancer Peroxides.

Iron-catalyzed dehydrogenative cross-coupling of carbonyl compounds with aliphatic peroxide was developed under mild conditions. A library of linear alkylated and arylated peroxides are synthesized in good to excellent yield. This method is highly selective and general for a range of biologically important derivatives of 2-oxindole, barbituric acid, and 4-hydroxy coumarin with a good functional group tolerance and without the cleavage of the peroxide bond. This peroxidation reaction is upscalable to grams and also synthesizable in continuous flow with increased safety in short duration. Mechanistic investigation reveals Fe-(II) undergoes redox type process to generate the radical intermediates, which subsequently recombine selectively to form the stable peroxides. The potential of peroxides is evaluated by cell viability assay and found to exhibit the good anticancer activity with minimum IC50= 5.3 μM.

HBr-Promoted Sulfenylation of Pyrazolones and 4-Hydroxycoumarins with N-(Organothio)succinimides

HBr-Promoted Sulfenylation of Pyrazolones and 4-Hydroxycoumarins with N-(Organothio)succinimides

One-pot two-step synthesis of 3-iodo-4-aryloxy coumarins and their Pd/C-catalyzed annulation to coumestans.

An efficient protocol for the synthesis of various coumestans from the intramolecular annulation of 3-iodo-4-aryloxy coumarins through C–H activation has been developed. When 3-iodo-4-aryloxy coumarins were treated with 10% Pd/C (0.3 mol% Pd) in the presence of sodium acetate, the corresponding coumestans were produced in good to excellent yield. Reusability of the palladium catalyst was investigated in up to three consecutive cycles and it was found that the yield of the reaction was almost unaltered. Sequential iodination and O-arylation of 4-hydroxy coumarins leading to the 3-iodo-4-aryloxy coumarins were also achieved in a one-pot two-step process starting from aryl iodides in high yield. Pivalic acid was revealed to be the most effective additive for the later method to produce 3-iodo-4-phenoxy coumarins. Different functional groups bearing electron-donating as well as withdrawing groups are also tolerant to the reaction conditions.

Regioselective annulation of propargyl alcohols with ambident-enols: A Ca(II)-catalyzed trisubstituted benzochromene synthesis

Highly regioselective, 6-endo cyclization between propargyl alcohols and ambident enols such as naphthols, 4-hydroxy coumarin, cyclohexane-1,3-dione, 5,5-dimethylcyclohexane-1,3-dione is described using Ca(OTf)2 under solvent free conditions. The reaction proceeds through a cascade annulation which involves an etherification, Claisen type rearrangement, allene formation and endocyclization. Further, we extended this method to the synthesis of iodo-derivative and demonstrated the reactivity in cross-coupling reactions.

Oxidative cyclisation and methylene insertion in 1,3-indandione derivatives .The mechanistic studies

Dimethyl sulphoxide activated by acetic-anhydride introduces methylthiomethyl group into phenols,oxidises certain medicinally useful secondary alcohols to their corresponding ketones and brings about oxidative rearrangements in different substrates.It converts 4-hydroxy coumarins and dicoumarols,under varying conditions,to a variety of products of both pharmaceutical and mechanistic interest.
 When1,3-indandione (1) was interacted with this versatile reagent at water bath temperature,it afforded an ylide (2) and an oxidative cyclisation product (3).However,its interaction with Ar –CH = (CN)R,leads to the formation of a mechanistically interesting compound,indeno[1,2-b]-4H pyran(4). 
 DMSO alone has been used as a reagent and yields a number of products of mechanistic interest with different substrates.When 1,3-indandione (1) was refluxed with DMSO alone at elevated temperature,it results the formation of poly(methylene-bis) 1,3-indandione(5) involving methylene group insertion between different 1,3-indandione moieties.Methylene insertion has also been observed when 1,3-indandione (1) was condensed with formaldehyde in presence of alkali carbonates or primary amines to yield (6)and(7) respectively.

Coumarin sulfonates: New alkaline phosphatase inhibitors; in vitro and in silico studies

A library of coumarin derived sulfonyl esters (1–38) was synthesized by reacting various hydroxy coumarins with different alkyl and aryl sulfonyl chlorides. All compounds were evaluated for their potential to inhibit alkaline phosphatases (hTNAP and hIAP). Most of the compounds were found to be inhibitors of APs. Compound 20 was found to be the most active hIAP inhibitor (IC50 = 1.11 ± 0.15 μM), whereas, compound 13 was found to be the most active hTNAP inhibitor (IC50 = 0.58 ± 0.17 μM). Detailed structure activity relationship studies (SAR), and molecular docking studies were carried out to identify structural elements necessary for AP inhibition, in addition to rationalize most probable binding site interaction of the inhibitors with the AP enzymes.

Dimethyl Sulphoxide a Useful Reagent for Organic Synthesis

Dimethyl sulphoxide as a reagent brings about N-methylthiomethylation and N,N/-methyl -thiomethylation in substituted barbituric acids. It converts 4-acetoxy coumarins to corresponding ylides and brings about methylene insertion in 1,6-naphtharidenes at reflux temperature.DMSO activated by trifluoro-aceticanhydride brings about formation of mono, bis and tris-sulphonic substituted derivatives when interacted with cyclo pentadiene and trimethylsilyl cyclopentadiene.This reagent converts 3-Nitro-4-hydroxy coumarins to salicylic acid in dichloromethane at low temperature.DMSO-acetic anhydride reagent converts enols to sulphur ylides, introduces methylthiomethyl group into phenols and oxidizes secondary alcohols to corresponding ketones. It brings about oxidative rearrangement in polyporic acid and converts 4-hydroxy coumarins and its 3-substituted derivatives into a wide range of products under different conditions.DMSO-SO3 pyridine complex in presence of triethyl amine oxidizes cis-diols to corresponding quinones.DMSO-activated by N-bromosuccinimide brings about methylation of alcohols and converts diols to their corresponding methylene-acetals.

An efficient four-component reaction for the synthesis of chromeno[4,3-b]quinolone derivatives

Chromenoquinolines have been prepared via an efficient one-pot, multi-component reaction of 4-hydroxy coumarin, aqueous ammonia, dimedone and different aldehydes.

Synthesis and Fluorescence Properties of New Rhodamine 6G Derivarives Containing Hydroxy Coumarin Moiety

Synthesis and Fluorescence Properties of New Rhodamine 6G Derivarives Containing Hydroxy Coumarin Moiety

Coumarin sulfonates: As potential leads for ROS inhibition

Coumarin sulfonates 4–43 were synthesized by reacting 3-hydroxy coumarin 1, 4-hydroxy coumarin 2and6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC50=54.2±9.2μM). Eleven compounds 6 (IC50=46.60±14.6μM), 8 (IC50=11.50±6.5μM), 15 (IC50=21.40±12.2μM), 19 (IC50=5.75±0.86μM), 22 (IC50=10.27±1.06μM), 23 (IC50=33.09±5.61μM), 24 (IC50=4.93±0.58μM), 25 (IC50=21.96±14.74μM), 29 (IC50=12.47±9.2μM), 35 (IC50=20.20±13.4μM) and 37 (IC50=14.47±5.02μM) out of forty demonstrated their potential suppressive effect on production of reactive oxygen species (ROS) as compared to ibuprofen. All the synthetic derivatives 4–43 were characterized by different available spectroscopic techniques such as 1H NMR, 13C NMR, EIMS and HRMS. CHN analysis was also performed.

Synthesis of 4-hydroxy coumarin dyes and their applications

PurposeThe present study aims to focus on the possibility of developing new eco-friendly azo dyes with good colouristic application properties, exhibiting biological and pharmacological activities.Design/methodology/approachCoupling of 4-hydroxycoumarin with a variety of aromatic diazonium salts of 2-aminothiazole, 2-aminobenzothiazole, 4-aminoantipyrine, 4-aminoacetophenone, adenine sulphate, a-naphthylamine and sulphadimidine to produce novel azo dyes. The compounds were fully characterised using spectroscopic and analytical methods. All of the compounds were tested for their antimicrobial, anticancer and antioxidant activities. The prepared dyestuffs were dyed on polyester fabrics and subsequently their dyeing properties, light, washing, perspiration, rubbing and sublimation fastness were determined.FindingsThe spectroscopic data of the synthesised compounds have provided decisive evidence that such compounds exist in the solid state as the azo-dike to form C and in solution in equilibrium tautomer forms A, B and D. The prepared dyestuffs are suitable for either heat transfer printing or traditional printing on polyester and nylon 6 fabrics. The prints obtained from the dyes possess high colour strength, as well as good overall fastness properties. Also the synthesised compounds exhibit good biological and pharmacology activity.Research limitations/implicationsSynthesis of these seven azo dyes for textile dyeing had never been reported previously.Practical implicationsThe dyestuffs derived from 4-hydroxycoumarin are reasonable azo disperse dyestuffs giving good all round fastness properties on polyester fabrics.Social implicationsProduction of less expensive and new eco-friendly dyes exhibit antimicrobial and anticancer activity.Originality/valueIt provided a potentially simple way to synthesize novel coumarin azo-dyes exhibit good biological and pharmacology activity and also exhibit good overall fastness properties.

Polyethylene glycol in water: Simple, efficient, and catalyst-free synthesis of 4H-pyran derivatives

ABSTRACTA green, one-pot, multicomponent method for the synthesis of diverse library of 4H-pyran derivatives such as 4-phenyl-4H-pyrans, spirochromenes, and dihydropyrano[3,2-c]chromines was developed using polyethylene glycol (PEG-600) as promoting reaction medium in water. The 4-phenyl-4H-pyran dihydropyrano[3,2-c]chromine derivatives were synthesized by a three-component reaction of aromatic aldehyde, malononitrile, and cyclic 1,3-dione/4-hydroxy coumarin at room temperature and reflux respectively. The promising points for the present methodology are efficiency, generality, high yield, short reaction time, cleaner reaction profile, ease of product isolation, potential to recycle reaction medium, and agreement with green chemistry protocols, making it a useful and attractive process for the synthesis of 4H-pyran derivatives.

A clean synthesis of bis(indolyl)methane and biscoumarin derivatives using P4VPy–CuO nanoparticles as a new, efficient and heterogeneous polymeric catalyst

A mild, simple, and efficient procedure has been developed for the synthesis of bis(indolyl)methanes and 3,3′-(arylmethylene)-bis-(4-hydroxy coumarins) using P4VPy–CuO nanoparticles as a heterogeneous polymeric catalyst.

Synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazole] and spiro[indoline-3,4′-pyrano[2,3-c]chromene] derivatives using silica-bonded ionic liquids as a recyclable catalyst in aqueous medium

Silica-bonded ionic liquids is employed as a recyclable catalyst for the synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] via one-pot condensation reaction of isatin, activated methylene reagents, and 3-methyl-l-phenyl-5-pyrazolone in refluxing aqueous medium in good to high yields. Also, these silica-bonded ionic liquids were used as catalysts for the synthesis of spiro[indoline-3,4′-pyrano[2,3-c]chromene derivatives in refluxing aqueous medium in high yields. Catalyst could be recycled for several times without any additional treatment. Silica-bonded ionic liquids is employed as a recyclable catalyst for the synthesis of spiro[indoline-3,4′-pyrano[2,3-c]pyrazoles] and spiro[indoline-3,4′-pyrano[2,3-c]chromene via one-pot condensation reaction of isatin, activated methylene reagents, and 3-methyl-l-phenyl-5-pyrazolone or 4-hydroxy coumarin respectively in refluxing aqueous medium in good to high yields.

Synthesis, structural analysis, spectrophotometric measurements and semiconducting properties of 3-phenyl azo-4-hydroxycoumarin thin films

3-phenyl azo-4-hydroxycoumarin, PAHC, compound was synthesized by reacting aniline diazonium salt with 4-hydroxy coumarin. The thin films of PAHC were prepared on the glass and quartz substrates by thermal evaporation technique under vacuum pressure 10−5 mbar. The structure of thin films was characterized using X-ray diffraction, XRD, and Fourier transformation infrared, FTIR, techniques. The XRD pattern for the pristine PAHC thin film showed nanocrystallites distributed in amorphous matrix. Annealing at 423K improved the crystallinity of films and the crystallite size is in the range 23–36nm. FTIR showed different vibrational modes, observed in infrared spectra of the powder, pristine and annealed thin films, were assigned to the molecular bonding structure of PAHC compound. The optical properties of PAHC thin films were investigated by the spectrophotometer measurements of the pristine and annealed PAHC films in the range 200–2100nm. The refractive and absorption indices of the pristine and annealed PAHC films were calculated from measured transmittance and reflectance data. The results showed that the refractive and absorption indices of thin films are influenced with increasing annealing temperature. The direct allowed transitions were the most probable transition and the optical band gap was found to vary from 2.14 to 2.21eV with increasing annealing temperature. The single oscillator model was applied in the normal region of dispersion spectrum to determine the dispersion parameters and it is noted that they are decreased with annealing temperature. The AC electrical conductivity, σAC, and the real and imaginary parts of dielectric constants measurements were investigated in temperature range 304–413K and frequency range 0.1–100kHz; they confirmed semiconductor behavior of the PAHC films.

Cosolubilization of Coumarin30 and Warfarin in Cationic, Anionic, and Nonionic Micelles: A Micelle-Water Interfacial Charge Dependent FRET.

Solubilization of structurally varied coumarins, viz., Warfarin (WF; a 4-hydroxy coumarin) and Coumarin30 (C30, a 7-amino coumarin) individually and in mixed states (cosolubilization) within the aqueous surfactant self-assemblies of varying architectures has been explored, exploiting steady-state, time-resolved fluorimetric, and spectrophotometric techniques. Cosolubilization studies within micelles, which have rarely been done in the literature, were specifically undertaken with the aim of understanding the effect of micelles on their photophysical phenomena when simultaneously present within these nanocarriers and assess their prospective use as an efficient FRET pair. WF solubilizes within CTAB micelles, whereas little or no solubilization is observed in Brij30 and SDS micelles. On the other hand, C30 solubilizes deep into the palisade layer of CTAB micelles, between negatively charged head groups in SDS micelles and between OE groups in Brij30 micelles. C30 and WF maintain their solubilization sites during cosolubilization. In SDS and Brij30 micelles, an increase in WF causes fluorescence quenching of C30 molecules, while in CTAB, an increase in WF causes an increase in fluorescence of C30 by excited WF molecules indicating FRET between the two molecules.

Synthesis and Molecular Docking Study of Novel Chromeno-chromenones as Anti-HIV-1 NNRT Inhibitors

<sc>l</sc>-Proline has been employed efficiently for the synthesis of chromeno-chromenone derivatives via a one-pot, three component condensation reaction of salicylaldehydes, 4-hydroxy coumarin, and indole or barbituric acid. The simple procedure and good to excellent yields (78–90%) are notable features of the method. The obtained derivatives were studied for their molecular docking as an anti-HIV-1 RT.

In vitro inhibition effect of some coumarin compounds on purified human serum paraoxonase 1 (PON1)

Human serum paraoxonase 1 (PON1; EC 3.1.8.1) is a high-density lipoprotein associated, calcium-dependent enzyme that hydrolyses aromatic esters, organophosphates and lactones and can protect the low-density lipoprotein against oxidation. In this study, in vitro effect of some hydroxy and dihydroxy ionic coumarin derivatives (1–20) on purified PON1 activity was investigated. Among these compounds, derivatives 11–20 are water soluble. In investigated compounds, compounds 6 and 13 were found the most active (IC50 = 35 and 34 µM) for PON1, respectively. The present study has demonstrated that PON1 activity is very highly sensitive to studied coumarin derivatives.

Biological evaluation and spectral characterization of 4-hydroxy coumarin analogues

Abstract Objective The development of antibiotic resistance has recently been recognized as a global health problem. This study was designed to develop new potent molecules that are economic and minimally toxic. The research examined a novel one-step synthetic procedure of bioactive 3-arylazo-substituted coumarin derivatives ( 4i – 4v ) and further evaluated their biological actions. Methods Male and female Wistar rats of appropriate age weighing 180–200 g were used to assess the wound incision, wound excision, acute toxicity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) models. The synthesized compounds were structurally interpreted with Differential Screening Calorimetry (DSC), FT/IR, 1H Nuclear Magnetic Resonance (NMR), LC-MS, UV-Visible and elemental analysis. The synthesized compounds were screened to investigate their in vitro antimicrobial, antioxidant and wound healing activities. Results A series of 4-hydroxy-3-(arylazo) coumarin ( 4i – 4v ) analogues were synthesized by coupling five different aryl diazonium salts with 4-HC in the presence of a 10% NaOH solution. The majority of the compounds showed significant antimicrobial, wound healing and antioxidant properties. The most potent compounds identified in the analysis were 4i v and 4e . Conclusion This study justifies that both aryl and hetero arylazo analogues of 4-hydroxy coumarin possess significant antimicrobial, wound healing and antioxidant properties.