Synthesis Of Coumarins Research Articles

Design, Synthesis, and Anticancer Evaluation of New Coumarin and Pyrazole Derivatives Bearing Benzenesulfonamide Moiety

Design, Synthesis, and Anticancer Evaluation of New Coumarin and Pyrazole Derivatives Bearing Benzenesulfonamide Moiety

Synthesis and characterization of coumarin based 1, 3, 4-oxadiazole: Exploring optoelectronic applications, thermal properties and theoretical study

A novel 1,3,4-oxadiazole linked coumarin dyes have been synthesised and are characterised by IR, NMR and Mass analysis. Several coumarin and oxadiazole derivatives have been patented for a variety of optoelectronic applications such as; fluorescent materials, photographic sensitizers, optical brighteners and organic light emitting diodes etc. Hence these new class of organic compounds were examined for their fluorescent properties and found to emit green light in the visible region of the spectrum with very high stokes shift values. The electronic structure of synthesized coumarin-based donor-π-acceptor (D-π-A)-type organic dyes has been examined by using Density Functional theory (DFT). TGA and DSC analysis of the compounds shows that, they are highly stable (>250 °C).

Design, synthesis and antitumor activity of coumarin, isoxazole, pyrazole, pyridine and pyrimidine compounds: 3β-hydroxypregn-5-ene-20-one derivatives

In continuation of our reserach for synthesizing heterocyclic derivatives with a broad range of biological activities, the current research was performed to synthesize 3β-hydroxypregn-5-ene-20-one derivatives of coumarin, isoxazole, pyrazole, pyridine and pyrimidine and screen for antitumor activity. Synthesis of amino-thiopephen derivatives (1a-1b) was performed through reaction of 3β-hydroxypregn-5-ene-20-one with ethyl cyanoacetate or malononitrile and sulphur. 3β-Hydroxypregn-5-ene-20-one was reacted with ethyl cyanoacetate in the presence of hydrazine, urea or thiourea to obtain aminopyrazole (3), aminopyrimidine (4a-4b) derivatives, respectively. The amino-thiophene derivatives (1a-1b) further reacted with either phenylisothiocyanate or benzoylisothiocyanate to form fused thienopyrimidine derivatives (5a-5d). The products 1a and 1b were also treated with ethyl cyanoacetate to afford cyanoacetamidothiophene derivatives (6a-6b) which were converted to fused thienopyridone derivatives (7a-7b) through cyclization reaction. The compounds 6a and 6b were allowed to react with different carbonyl compounds including salicyaldehyde, cyclopentanone-sulphur mixture, acetylacetone and malonaldehyde to prepare coumarin (8a-8b), cyclopentylthiophene (9a-9b) and 2-pyridinone (10a-10d) derivatives respectively. Furthermore, the reactions of hydroxylamine hydrochloride and benzoylacetonitrile with the compounds 6a-6b separately afforded new aminoisoxazole (12a-12b) and phenylpyridone (14a-14b) derivatives, respectively. The structures of new products were established through IR, 1H NMR, 13C NMR spectroscopic and mass spectrometric analysis. The synthesized compounds (1a-1b to 14a-14b) displayed in-vitro antitumor activity against human cell-lines, including MCF-7 (breast adenocarcinoma), SF-268 (CNS cancer) and NCI-H460 (non-small lung cancer cell). The results suggested that all the screened products exhibited cell growth inhibitory activity in a dose-dependents manner. However, the compound 12a showed highest level of inhibition against all three cell-lines.

Sufficient coumarin accumulation improves apple resistance to Cytospora mali under high potassium status.

Cytospora canker, caused by Cytospora mali, is the most destructive disease in production of apples (Malus domestica). Adding potassium (K) to apple trees can effectively control this disease. However, the underlying mechanisms of apple resistance to C. mali under high-K status remain unknown. Here, we found that high K (HK, 9.30 g/kg) apple tissues exhibited high disease resistance. The resistance was impeded when blocking K channels, leading to susceptibility even under HK conditions. We detected a suite of resistance events in HK apple tissues, including upregulation of resistance genes, callose deposition, and formation of ligno-suberized tissues. Further multi-omics revealed that the phenylpropanoid pathway was reprogrammed by increasing K content from low K (LK, 4.30 g/kg) status, leading to increases of 18 antifungal chemicals. Among them, the physiological concentration of coumarin (1,2-benzopyrone) became sufficient to inhibit C. mali growth in HK tissues, and exogenous application could improve the C. mali resistance of LK apple branches. Transgenic apple calli overexpressing beta-glucosidase 40 (MdBGLU40), which encodes enzyme for coumarin synthesis, contained higher levels of coumarin and exhibited high resistance to C. mali even under LK conditions. Conversely, suppression of MdBGLU40 through RNAi reduced coumarin content and resistance in HK apple calli, supporting the importance of coumarin accumulation in vivo for apple resistance. Moreover, we found that the upregulation of transcription factor MdMYB1r1 directly activated MdBGLU40, and the binding affinity of MdMYB1r1 to the MdBGLU40 promoter increased in HK apple tissue, leading to high levels of coumarin and resistance in HK apple. Overall, we found that accumulation of defensive metabolites strengthened resistance in apple when raising K from insufficient to optimal status, and these results highlight the optimization of K content in fertilization practices as a disease management strategy.

Comprehensive multi-omics analysis reveals the importance of CtCOSY in the energy metabolism and coumarin biosynthesis in Clematis terniflora DC

Coumarin synthase (COSY) is the key enzyme involved in the coumarin biosynthesis. Although it has been identified firstly in Arabidopisis thaliana, there is little known about the COSY gene function in Clematis terniflora DC. Our previous study indicated that the contents of coumarins in C. terniflora leaf were increased under ultraviolet-B radiation and dark treatments (UV-D). To reveal the function of COSY in C. terniflora and its role in response to UV-D stress, the functional characterization of CtCOSY which was identified as a BADH acyltransferase was performed. The results showed that coupled reaction of CtCOSY with 4-coumarinyl CoA-ligase in vitro to produce umbelliferone. Moreover, the functions of CtCOSY in response to UV-D stress was studied using proteomic and metabolomic techniques. Multi-omics analyses of CtCOSY-silenced C. terniflora indicated that as well as a limitation of coumarin synthesis, aspects of the energy metabolism, such as the TCA cycle, were disturbed in these plants. Under UV-D stress, CtCOSY affected the biosynthesis of phenylpropanoids in C. terniflora, resulting in the improvement of coumarin biosynthesis and affecting purine metabolism. This study provides the evidences of CtCOSY responsible for the biosynthesis of coumarin in C. terniflora and the resistance to UV-D stress.

Visible Light-Induced Cross-Dehydrocoupling of 3-Cyanocoumarins with Unactivated Aliphatic Aldehydes Enables Access to 4-Acylated Coumarins.

We report visible light-induced cross-dehydrocoupling of 3-cyanocoumarins with unactivated aliphatic aldehydes for the direct synthesis of 4-acylated coumarins. Inexpensive and readily available (n-Bu)4NBr was used as a precursor of the hydrogen atom transfer (HAT) catalyst and [Ir(ppy)2(dtbbpy)PF6] as a photocatalyst. A variety of aldehydes including linear, branched, cyclic, and α,β-unsaturated aliphatic aldehydes were suitable for this reaction yielding the desired acylated coumarin derivatives in 41-98% yields. This method provides a mild, atom-economical, and environmentally friendly synthetic route for the direct acylation of 3-cyanocoumarins. This is the first example so far of C-4 aliphatic acylation of coumarins.

Four Component One Pot Synthesis of Benzyl Pyrazolyl Coumarin Derivatives Catalyzed by Metal-Free, Heterogeneous Chitosan Supported Ionic Liquid Carbon Nanotubes

In this present communication, four component, one pot synthesis of benzyl pyrazolyl coumarin (5a-m) derivatives achieved from the condensation of phenyl hydrazine (1), ethyl acetoacetate (EAA, 2), various substituted benzaldehyde (3), and 4-hydroxy coumarin (4) in EtOH/H2O using metal-free chitosan supported ionic liquid carbon nanotubes (CSIL@CNTs, 10 mol%) as heterogeneous catalyst reflux at 50 °C for 25–30 min. The optimized conditions and excellent yields of the products were reported. All the synthesized compounds were charecterized by the spectroscopic methods. The main advantages of this reported method using CSIL@CNTs. leads to effective conversions were achieved under reflux conditions without the need of an inert atmosphere. In adition, shorter reaction time, simple work up procedure, easy preparation of the catalyst, and chemoselectivity were siginificantly recorded.

A facile visible-light-induced one-pot synthesis of 3-alkyl coumarins from simple salicylaldehydes

An efficient and mild one-pot stepwise method to synthesize 3-alkyl coumarins is reported. Various 3-alkyl coumarins were synthesized under 3 W blue LEDs irradiation at room temperature from cheap and easily available salicylaldehydes. Based on the results of control experiments and the literature, it is found that the reaction might proceed via Wittig/cyclic condensation/radical alkylation processes.

Pd@GO catalyzed stereo- and regio-selective addition of arenes to alkynes and synthesis of coumarins via C-H functionalization.

A stereo- and regio-selective addition of arenes to alkynes via C-H bond functionalization has been developed using palladium nanoparticles supported on graphite oxide (Pd@GO) as the reusable catalyst. The prepared catalyst was characterized by various spectroscopic techniques such as FT-IR, TEM, SEM, EDX, P-XRD, and XPS analysis. The thermal stability of the catalyst was established by TGA. The C-H functionalized products were obtained in good to excellent yields (69-92%) at room temperature. The methodology further extended to the synthesis of biologically and pharmaceutically important coumarin molecules from phenols and alkynes. Good to excellent yields of the coumarins (74-92%) were obtained. After the reaction, the catalyst was separated by centrifugation followed by filtration. The recovered catalyst was washed and reused up to five cycles. The advantages of this method are the simple procedure of the catalyst preparation, high catalytic efficiency, high selectivity, good functional group tolerance, low catalyst loading, and gram-scale synthesis.

Barium silicate nanoparticles, an efficient catalyst for one-pot green synthesis of α-benzyl amino coumarin derivatives as potential chemotherapeutic agents.

A new, simple, and efficient method for synthesis of α-benzyl amino coumarin and its derivatives (1-24) is described via a one-pot, three-component condensation of aromatic aldehydes, amine, and 4-hydroxycoumarin under green chemistry conditions: water as a solvent and BaSiO3 nanoparticles as catalyst. BaSiO3 nanoparticles and all synthesized derivatives were characterized by multiple methods including; XRD, NMR, and FE-SEM. This method which gives higher yields, is also less expensive, and more environmentally friendly compared with other methods in the literature. In silico physicochemical and pharmacokinetics analyses were done on all synthesized compounds and indicated that these α-benzyl amino coumarins would be effective scaffolds for the future development of chemotherapeutic agents.

Study on effective synthesis of 7-hydroxy-4-substituted coumarins

Abstract Many coumarin derivatives have good biological activity and application value in fluorescent probes. Therefore, synthetic routes to coumarin derivatives have also attracted the attention of many research groups. In this work, based on the Pechmann coumarin synthesis method, the influence of various Lewis acids on the reaction was discussed, and the optimal synthesis conditions of 7-hydroxy-4-substituted coumarins were explored. Based on the experimental results, a possible mechanism was proposed, which provides a reference for future industrialized production of coumarins.

Synthesis and Cytotoxicity Evaluation of Novel Coumarin-Palladium(II) Complexes against Human Cancer Cell Lines.

Two newly synthesized coumarin-palladium(II) complexes (C1 and C2) were characterized using elemental analysis, spectroscopy (IR and 1H-13C NMR), and DFT methods at the B3LYP-D3BJ/6-311+G(d,p) level of theory. The in vitro and in silico cytotoxicity of coumarin ligands and their corresponding Pd(II) complexes was examined. For in vitro testing, five cell lines were selected, namely human cervical adenocarcinoma (HeLa), the melanoma cell line (FemX), epithelial lung carcinoma (A549), the somatic umbilical vein endothelial cell line (EA.hi926), and pancreatic ductal adenocarcinoma (Panc-1). In order to examine the in silico inhibitory potential and estimate inhibitory constants and binding energies, molecular docking studies were performed. The inhibitory activity of C1 and C2 was investigated towards epidermal growth factor receptor (EGFR), receptor tyrosine kinase (RTK), and B-cell lymphoma 2 (BCL-2). According to the results obtained from the molecular docking simulations, the inhibitory activity of the investigated complexes towards all the investigated proteins is equivalent or superior in comparison with current therapeutical options. Moreover, because of the low binding energies and the high correlation rate with experimentally obtained results, it was shown that, out of the three, the inhibition of RTK is the most probable mechanism of the cytotoxic activity of the investigated compounds.

Design, Catalyst-Free Synthesis of New Novel α-Trifluoromethylated Tertiary Alcohols Bearing Coumarins as Potential Antifungal Agents

A new method for the synthesis of α-trifluoromethylated tertiary alcohols bearing coumarins is described. The reaction of 3-(trifluoroacetyl)coumarin and pyrrole provided the target compounds with high yields under catalyst-free, mild conditions. The crystal structure of compound 3fa was investigated by X-ray diffraction analysis. The biological activities, such as in vitro antifungal activity of the α-trifluoromethylated tertiary alcohols against Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Rhizoctonia solani Kuhn, and Phytophthora parasitica var nicotianae, were investigated. The bioassay results indicated that compounds 3ad, 3gd, and 3hd showed broad-spectrum antifungal activity in vitro. Compound 3cd exhibited excellent fungicidal activity against Rhizoctonia solani Kuhn, with an EC50 value of 10.9 μg/mL, which was comparable to that of commercial fungicidal triadimefon (EC50 = 6.1 μg/mL). Furthermore, molecular docking study suggested that 3cd had high binding affinities with 1W9U, like argifin.

Development and Application of a Supramolecular Brønsted Acid Catalyst Based on the Noria Macrocycle.

The synthesis of derivatives of the Noria macrocycle and the structurally similar macrocycle, R3, each containing 12 sulfonic acid groups, is reported. Herein, we demonstrate their utility as reusable Brønsted acid catalysts for the Biginelli synthesis of dihydropyrimidinones and the Pechmann synthesis of coumarins. We also demonstrate that the supramolecular structure directs the reagents to interact with the sulfonic acid catalytic sites, thus increasing the catalyst's efficiency compared to other monomeric, macrocyclic, and polymeric sulfonic acid catalysts.

Greener Syntheses of Coumarin Derivatives Using Magnetic Nanocatalysts: Recent Advances.

Coumarins (2H-1-benzopyran-2-ones) are an important group of biological heterocyclic compounds present in various parts of many plant species, encompassing an array of biological and pharmaceutical activities. In view of the importance of coumarins in heterocyclic chemistry and biological sciences and recent advances in the design of magnetic nanocatalysts, we present herein recent developments pertaining to their synthesis exclusively using magnetic nanoparticles, which can be retrieved easily and thus conform to the tenets of greener synthesis. The preparation of various types of coumarins such as Pechmann-based coumarins, bis coumarins, pyranocoumarins, and coumarin derivatives bearing amine moiety, linked to nicotinonitriles, N-coumarin-2-furanone, and pyrrole-linked chromene derivatives using nanocatalysts with a Fe3O4 core are described. This review covers the synthetic developments in the recent years 2012-2021 and focuses entirely on the synthesis of coumarins in the presence of magnetic nanocatalysts using greener approaches such as solvent-free conditions or deploying alternative activation methods, namely microwave or ultrasound irradiation.

Coumarin‐based Chemosensors for Metal Ions Detection

AbstractCoumarins, due to their intense and persistent emission of fluorescence, structural flexibility, and excellent biocompatibility, have become a popular choice in developing new fluorescent chemosensors. Coumarins have long been used for sensing anions, cations, chemically reactive nitrogen, oxygen, sulfur‐containing species, and small molecules. They have also been shown to have applicability in imaging, biology, and medical research. Due to the widespread use and excellent biological activity, hundreds of such coumarin motifs have either been isolated from nature or synthesized in a laboratory. This review covers all the developments pertaining to the synthesis and use of coumarin for sensing a variety of metal ions (alkali, alkaline earth, transition, heavy, and noble metal ions). This comprehensive review includes an overview of the coumarin‐based chemosensor‘s pH limit, detection limit, and binding mode. A brief explanation of the stoichiometric ratio between metal and chemosensor moiety and the applicability of each chemosensor is also given.

Novel green sulfated phosphotungstic acid supported on MCM-41-coated NiFe2O4 MNPs for xanthene and coumarin synthesis

Novel green sulfated phosphotungstic acid supported on MCM-41-coated NiFe2O4 MNPs for xanthene and coumarin synthesis

Synthesis, biological evaluation, and molecular dynamics of novel coumarin based phosphorothioates as cholinesterase inhibitors

Inhibition of acetylcholinesterase has been validated as an effective target for treatment of Alzheimer's disease by increasing the levels of acetylcholine and improving the communication between the neuronal cells. Literature reports revealed that coumarins and phosphorothioates were shown to be promising scaffolds as acetylcholinesterase inhibitors. A series of novel chroman-4one derivative moieties (6a-6d, 7b-7d, 8–11) were synthesized with good to excellent yield by reactions of coumarin sulfonyl chlorides 1a, b with various di- and trialkylphosphites, Wittig reagents 4a-d, and the new products were evaluated for their cholinesterase (ChE) inhibitory activities. Structure–activity relationship study results showed that 7a is the most potent compound (anti AChE activity; IC50 = 0.73 μg/ ml), indicating the preference for hydrophobic interaction and Pi-stacked at the side chain of the molecule. This was supported further by molecular docking and dynamics studies of the most potent compound (7a against AChE), which revealed favored interactions with the ChE enzyme's binding pockets.

Solvent-free Pechmann synthesis of coumarins catalyzed by magnetic heterogeneous catalyst Fe3O4@rGO-NH

Solvent-free Pechmann synthesis of coumarins catalyzed by magnetic heterogeneous catalyst Fe3O4@rGO-NH

Potassium dihydrogen phosphate‐catalyzed synthesis of benzylpyrazolyl coumarin and pyrano [2,3‐c] pyrazole derivatives via cascade—One‐pot—Multicomponent reaction

AbstractA simple one‐pot protocol for the synthesis of benzylpyrazolyl coumarin and pyrano [2,3‐c] pyrazole derivatives in the presence of potassium dihydrogen phosphate (KH2PO4) has been developed. This cascade reaction provides many advantages like environmentally benign reaction, mild reaction conditions, inexpensive catalyst, simple operation, easy workup procedure, a wide range of functional groups in good to excellent yields, and no need for column purification.