Furanone Derivatives Research Articles

Construction of Lactones via Ligand-Enabled Ni-Catalyzed Alkene Hydroxylarylation/Lactonization.

Here, we report the preparation of lactones via Ni-catalyzed alkene hydroxylarylation and sequential intramolecular lactonization with O2 as a green oxidant and oxygen source. The bulky 1,3-diketone ligand is crucial by enabling Ni-catalyzed hydroxylarylation of alkenes, providing numerous phthalide and furanone derivatives with high efficiency under mild conditions. The synthetic value of this methodology was further demonstrated by the efficient synthesis of typhaphthalide and a monoamine oxidase B inhibitor.

Organocatalyzed Synthesis of γ-Alkenyl Butenolides via Asymmetric Direct Vinylogous Conjugate Addition-Elimination of Substituted Furanone Derivatives to β-Phenylsulfonylenones.

A diaminomethylenemalononitrile organocatalyst efficiently promoted the asymmetric direct vinylogous conjugate addition of α-angelica lactone derivatives to β-phenylsulfonylenones, affording the corresponding γ-alkenyl γ-butenolides in high yields with excellent enantioselectivities (up to 97% ee) after the elimination of the phenylsulfonyl group. This study reports the first successful example of a stereoselective reaction using β-phenylsulfonylenone as the direct alkenyl donor.

Synthesis, insecticidal Activity, and molecular docking analysis of some benzo[h]quinoline derivatives against Culex pipiens L. Larvae

Some heterocycles bearing a benzo[h]quinoline moiety were synthesized through treating a 3-((2-chlorobenzo[h]quinolin-3-yl)methylene)-5-(p-tolyl)furan-2(3H)-one with four nitrogen nucleophiles comprising ammonium acetate, benzylamine, dodecan-1-amine, and 1,2-diaminoethane. Also, thiation reactions of furanone and pyrrolinone derivatives were investigated. The insecticidal activity of these compounds against mosquito larvae (Culex pipiens L.) was evaluated. All tested compounds exhibited significant larvicidal activity, surpassing that of the conventional insecticide chlorpyrifos. In silico docking analysis revealed that these compounds may act as acetyl cholinesterase (AChE) inhibitors, potentially explaining their larvicidal effect. Additionally, interactions with other neuroreceptors, such as nicotinic acetylcholine receptor and sodium channel voltage-gated alpha subunit were also predicted. The results obtained from this study reflected the potential of benzo[h]quinoline derivatives as promising candidates for developing more effective and sustainable mosquito control strategies. The ADME (absorption, distribution, metabolism, and excretion) analyses displayed their desirable drug-likeness and oral bioavailability properties.

The Repellent Capacity against Sitophilus zeamais (Coleoptera: Curculionidae) and In Vitro Inhibition of the Acetylcholinesterase Enzyme of 11 Essential Oils from Six Plants of the Caribbean Region of Colombia.

The repellent capacity against Sitophilus zeamais and the in vitro inhibition on AChE of 11 essential oils, isolated from six plants of the northern region of Colombia, were assessed using a modified tunnel-type device and the Ellman colorimetric method, respectively. The results were as follows: (i) the degree of repellency (DR) of the EOs against S. zeamais was 20-68% (2 h) and 28-74% (4 h); (ii) the IC50 values on AChE were 5-36 µg/mL; likewise, the %inh. on AChE (1 µg/cm3 per EO) did not show any effect in 91% of the EO tested; (iii) six EOs (Bursera graveolens-bark, B. graveolens-leaves, B. simaruba-bark, Peperomia pellucida-leaves, Piper holtonii (1b*)-leaves, and P. reticulatum-leaves) exhibited a DR (53-74%) ≥ C+ (chlorpyrifos-61%), while all EOs were less active (8-60-fold) on AChE compared to chlorpyrifos (IC50 of 0.59 µg/mL). Based on the ANOVA/linear regression and multivariate analysis of data, some differences/similarities could be established, as well as identifying the most active EOs (five: B. simaruba-bark, Pep. Pellucida-leaves, P. holtonii (1b*)-leaves, B. graveolens-bark, and B. graveolens-leaves). Finally, these EOs were constituted by spathulenol (24%)/β-selinene (18%)/caryophyllene oxide (10%)-B. simaruba; carotol (44%)/dillapiole (21%)-Pep. pellucida; dillapiole (81% confirmed by 1H-/13C-NMR)-P. holtonii; mint furanone derivative (14%)/mint furanone (14%)-B. graveolens-bark; limonene (17%)/carvone (10%)-B. graveolens-leaves.

Siamfuranones A–C, three novel furanone derivatives from the flowers of Uvaria siamensis and their biological activities

Three previously undescribed furanone derivatives named siamfuranones A–C (1–3), together with 11 known compounds (4–14), were isolated from the flowers of Uvaria siamensis. Their planar structures were determined through analysis of spectrometric and spectroscopic evidence, while electronic circular dichroism (ECD) calculations were used to determine their absolute configurations. In addition, gauge-including atomic orbitals (GIAO) NMR chemical shift calculation, supported by the advanced statistical method DP4 plus, was used to confirm the relative configuration of siamfuranone B (2). All the isolated compounds were evaluated against two cancer cell lines (A549 and Hela), and screened for antibacterial activities. Furthermore, they were assessed for cytotoxicity against a normal cell line (Vero cell).

Shedding light on Paraconiothyrium brasiliense: Secondary metabolites, biological activities, and computational studies

Fungi are renowned as a prolific source for the biosynthesis of therapeutically valuable metabolites. Paraconiothyrium genus (Leptosphaeriaceae) demonstrates remarkable potential for the biosynthesis of a wide array of metabolites, including macrolides, terpenoids, polyketides, phenolics, and furanones, which exhibit diverse bioactivities. The present review focused on the reported metabolites derived from Paraconiothyrium brasiliense, including their chemical structures and bioactive properties. Furthermore, it delves into the elucidation of the biosynthetic pathways for these metabolites. This review encompasses the description of over 92 compounds reported in the literature from 2010 to October 2023. In addition, in silico studies may explain the potential mechanisms underlying the neuroprotective properties of certain furanone derivatives against central nervous system disorders. Among the tested compounds against KEAP1 through Keap1/Nrf2 pathway-mediated neuroprotection, paraconfuranone I (48), paraconfuranone (50), and paraconfuranone L (51) displayed docking scores ranging from −6.158 to −6.612 kcal/mol, similar to the exciting reference compound which achieved the highest docking score of −6.633 kcal/mol. Moreover, new potential activities of some compounds as inhibitors against the LasR target of Pseudomonas aeruginosa were elucidated using molecular docking and absorption, distribution, metabolism, excretion, and toxicity prediction. Specifically, 1-(1’,2’-dideoxy-α-D-nucleopyranosyl)-β-carboline (73) had the highest docking score at −11.327 kcal/mol, followed by 1-acetyl-β-carboline (75) at −10.055 kcal/mol, in comparison to reference compound (docking score −10.023 kcal/ mol). In addition, ten other compounds displayed competitive docking scores ranging from −9.813 to −9.312 kcal/ mol. This suggested the potential of P. brasiliense as a promising lead for antibacterial and neuroprotective agents.

Intramolecular hydrogen bond activation for kinetic resolution of furanone derivatives by an organocatalyzed [3 + 2] asymmetric cycloaddition

A formal highly enantioselective organocatalyzed [3 + 2] cycloaddition of furanones and azomethine ylides paired to a highly efficient kinetic resolution is presented.

Synthesis of Phosphet-2-one Derivatives via Phosphinidene Transfer to Cyclopropenones.

We report the first synthesis and structural characterization of free, uncomplexed phosphet-2-ones. These unsaturated four-membered phosphacycles were prepared by phosphinidene transfer from dibenzo-7-phosphanorbornadiene compounds, RPA (A = C14H10, anthracene), to cyclopropenones in yields of up to 89%. Theoretical studies suggest that the reaction proceeds through ketene-ylide and ketene-phosphaalkene intermediates. Further transformations of the phosphet-2-ones led to the isolation of more phosphet-2-ones and 1,2-dihydrophosphetes, including two furanone derivatives which are postulated to be produced by intramolecular phosphine-catalyzed [3 + 2] annulations.

Two new furanone derivatives from the endophytic fungus Byssochlamys sp. and their cytotoxic activities

Two new furanone derivatives, byssochlanones A–B (1–2) were purified from the endophytic fungus Byssochlamys sp. isolated from the wetland plant, Phragmites australis. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compounds 1–2 represented typical furanone analogues which are not common in natural products. The absolute configuration of compounds 1–2 were identified through quantum-chemical electronic circular dichroism (ECD) calculation compared with their experimental CD. In addition, compounds 1–2 were tested for their cytotoxic activities against HCT-8 and Hela cancer cell lines, and compound 2 showed moderate activity against HCT-8 cells with IC50 value of 21.3 μM.

Solvent-solute interaction, thermodynamic behaviour, structural, chemical and anti-cancer biological properties of 3(2H)-furanone derivatives

In this work, the structures, reactivities, and electronic and biological properties of the 3(2H)-furanone derivatives, 2-hydroxy-2,5-diphenyl-4-(phenylamino)furan-3(2H)-one (HDPF), 2-methoxy-2,4,5-triphenylfuran-3(2H)-one (MTPF), 3-oxo-2,4,5-triphenyl-2,3-dihydrofuran-2-yl acetate (OTDF), and 2-chloro-2,4,5-triphenylfuran-3(2H)-one (CTPF), are explored via theoretical investigations using DFT (Density Functional Theory) techniques as the main tools for the study. The DFT studies include geometry optimisation, FMO (Frontier Molecular Orbital) analysis, theoretical UV studies, molecular electrostatic potential (MEP) investigations, non-linear optical (NLO) analyses, and the evaluation of thermodynamic parameters. Multiwfn 3.8 software is utilised to conduct the topological analyses. The ADME (Absorption, Distribution, Metabolism, Excretion) profiles are produced with the SwissADME online tool. The target proteins, MCL-1 (Myeloid cell leukemia-1), BCL-2 (B-cell lymphoma-2), and myeloblastin, are docked with the title molecules using AutoDock 1.5.6.

Copper‐Catalyzed Olefinic C(sp2)−H Activation/Carbene Insertion/Ester Hydrolysis/Cyclization with Aryl Diazo Esters for the Synthesis of Multisubstituted Furanones

AbstractA copper‐catalyzed olefinic C(sp2)−H activation/carbene insertion/ester hydrolysis/cyclization sequence has been developed for the synthesis of substituted 2(5H)‐furanones employing readily available enaminones and aryl diazo esters as substrates. This method features operationally simple and good functional group tolerance. The transformation could be scaled up to gram quantities and the obtained 2(5H)‐furanone derivatives could be easily converted to a wide range of useful synthetic building blocks, indicative of the applicability of the synthetic strategy. Isotope labeling experiments demonstrated the ester group of diazo esters was hydrolyzed during the reaction.

Elucidation of furanone as ergosterol pathway inhibitor in Cryptococcus neoformans

In the era of antiretroviral therapy, the prevalence of Cryptococcal infection among HIV patients in developed countries has decreased considerably. However, C. neoformans ranks top among the critical priority pathogen that affects a wide range of immunocompromised individuals. The threat of C. neoformans is because of its incredibly multifaceted intracellular survival capabilities. Cell membrane sterols especially ergosterol and enzymes of its biosynthetic pathway are considered fascinating drug targets because of their structural stability. In this study, the ergosterol biosynthetic enzymes were modeled and docked with furanone derivatives. Among the tested ligands Compound 6 has shown a potential interaction with Lanosterol 14 α-demethylase. This best-docked protein-ligand complex was taken further to molecular dynamics simulation. In addition, Compound 6 was synthesized and an in vitro study was conducted to quantify the ergosterol in Compound 6 treated cells. Altogether the computational and in vitro study demonstrates that Compound 6 has anticryptococcal activity by targeting the biosynthetic pathway of ergosterol. Communicated by Ramaswamy H. Sarma

Design and Synthesis of 4-Fluorophenyl-5-methylene-2(5H)-furanone Derivatives as Potent Quorum Sensing Inhibitors.

Quorum sensing inhibitors (QSIs) are a class of compounds that can reduce the pathogenicity of bacteria without affecting bacterial growth. In this study, we designed and synthesized four series of 4-fluorophenyl-5-methylene-2(5H)-furanone derivatives and evaluated their QSI activities. Among them, compound 23e not only showed excellent inhibitory activity against various virulence factors but also significantly enhanced the inhibitory activity of antibiotics ciprofloxacin and clarithromycin against two strains of Pseudomonas aeruginosa in vitro. What is even more exciting is that it remarkably increased the antibacterial effect in vivo in combination with ciprofloxacin in the bacteremia model infected with P. aeruginosa PAO1. Moreover, 23e had little hemolytic activity to mouse erythrocytes. Further, the results of GFP reporter fluorescence strain inhibition and β-galactosidase activity inhibition experiments demonstrated that 23e simultaneously targeted the three quorum sensing systems in P. aeruginosa. As a result, compound 23e could be used as an effective QSI for further development against bacterial infections.

Synthesis and antioxidant, antimicrobial, and antiviral activity of some pyrazole-based heterocycles using a 2(3H)-furanone derivative

Some pyrazole-based heterocycles such as pyrrolone, pyridazinone, and imidazole derivatives were synthesized utilizing the pyrazolyl-2(3H)-furanone derivative 3, which was obtained in a good yield via Perkin condensation of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with 3-(4-methylbenzoyl)propionic acid in the presence of cyclo-dehydrating agent (sodium acetate and acetic anhydride). Also, the acid hydrazide obtained was reacted with some carbonyl reagents such as acetic anhydride, benzoyl chloride, 4-chlorobenzaldehyde, and 1,3-diphenyl-4-formylpyrazole, aiming to achieve new pyrrolone derivatives. The antioxidant, antimicrobial, and antiviral activity screening of some synthesized compounds demonstrated that some of them offered strong potencies. An experimental trial was undertaken to explore the effect of different substances and applied against avian influenza HPAI-H5N1 (AIV) to evaluate the antiviral replication in specific pathogen-free chicken embryos. All the compounds were screened for their antimicrobial activities, and most of tested compounds showed potent inhibition growth activity toward Haemophilus (Gram-negative bacteria), Staphylococcus aureus (Gram-positive bacteria), and Candida albicans fungus. Upon antimicrobial screening, it was observed that the majority of the compounds were found to be active against Staphylococcus aureus, Haemophilus, and Candida albicans as compared to standard drugs. This experiment shows the potential usage of these compounds as antiviral agents and can be considered as a viable means to control the economically important avian influenza of poultry. These compounds can thus be recommended for their antiviral, antibacterial, and antifungal property and can very well be used as immunostimulants.

The Novel Chiral 2(5H)-Furanone Sulfones Possessing Terpene Moiety: Synthesis and Biological Activity.

Over the past decades, 2(5H)-furanone derivatives have been extensively studied because of their promising ability to prevent the biofilm formation by various pathogenic bacteria. Here, we report the synthesis of a series of optically active sulfur-containing 2(5H)-furanone derivatives and characterize their biological activity. Novel thioethers were obtained by an interaction of stereochemically pure 5-(l)-menthyloxy- or 5-(l)-bornyloxy-2(5H)-furanones with aromatic thiols under basic conditions. Subsequent thioethers oxidation by an excess of hydrogen peroxide in acetic acid resulted in the formation of the corresponding chiral 2(5H)-furanone sulfones. The structure of synthesized compounds was confirmed by IR and NMR spectroscopy, HRMS, and single crystal X-ray diffraction. The leading compound, 26, possessing the sulfonyl group and l-borneol moiety, exhibited the prominent activity against Staphylococcus aureus and Bacillus subtilis with MICs of 8 μg/mL. Furthermore, at concentrations of 0.4-0.5 μg/mL, the sulfone 26 increased two-fold the efficacy of aminoglycosides gentamicin and amikacin against S. aureus. The treatment of the model-infected skin wound in the rat with a combination of gentamicin and sulfone 26 speeded up the bacterial decontamination and improved the healing of the wound. The presented results provide valuable new insights into the chemistry of 2(5H)-furanone derivatives and associated biological activities.

Synthesis and antioxidant activity of some pyrazole-based heterocycles using a 2(3H)-furanone building block

Some pyrazole-based heterocycles, such as pyrrolone, pyridazinone, and imidazole derivatives were synthesized utilizing the pyrazolyl-2(3H)-furanone derivative 3, which was obtained in a good yield via Perkin condensation of 5-chloro-4-formyl-3-methyl-1-phenylpyrazole with 3-(4-methylbenzoyl)propionic acid in the presence of cyclo-dehydrating agent (sodium acetate and acetic anhydride). Also, the acid hydrazide obtained was reacted with some carbonyl reagents like acetic anhydride, benzoyl chloride, 4-chlorobenzaldehyde, and 1,3-diphenyl-4-formylpyrazole, aiming to achieve new pyrrolone derivatives. The antioxidant activity screening of some synthesized compounds demonstrated that pyridazinone and N-phenylhydrazide derivatives showed the most exceptional potencies.

Fabrication of Modified Chitosan with Furanone Derivatives and its Nanocomposites: Synthesis, Characterization and Evaluation as Anticancer Agents

Fabrication of Modified Chitosan with Furanone Derivatives and its Nanocomposites: Synthesis, Characterization and Evaluation as Anticancer Agents

Catalyst-free diazo cross-coupling to access useful 3(2H)-furanone derivatives.

Catalyst-free synthesis of 3(2H)-furanone derivatives has been achieved from metal-free cross-coupling of α-diazo ester and α-aryldiazo ketones. This reaction sequence comprises a prior Wolff rearrangement of α-aryldiazo ketones to 2-arylketenes, which are trapped in situ with α-diazo esters to form cyclopropanones before undergoing oxa-Nazarov cyclization.

Synthesis of 3(2H)-furanone derivatives: p-TsOH/halotrimethylsilane promoted cycloketonization of γ-hydroxyl ynones.

A p-TsOH/halotrimethylsilane facilitated cycloketonization of γ-hydroxyl ynones is detailed. This methodology enables the one-step synthesis of polysubstituted 3(2H)-furanone products. It is remarkable that the reaction exhibits excellent regio- and chemoselectivity by the addition of very small quantities of p-toluenesulfonic acid and water.

Cp*RhCl2]2catalyzed three-component coupling cyclization of 2,3-allenoic acids with 2,3-allenols in the presence of Cu(OAc)2·H2O

A [Cp*RhCl2]2catalyzed three-component coupling cyclization of 2,3-allenols and 2,3-allenoic acids affording furanone derivatives with an acetate functionality was established. Isotopic labelling experiments unveiled a unique mechanism.