Pyrone Ring Research Articles

PH-Dependent Photoinduced Interconversion of Furocoumaric and Furocoumarinic Acids.

Photo-controlled or photo-regulated molecules, especially biologically active and operating in physiological conditions, are in steady demand. Herein, furocoumaric and furocoumarinic acids being (Z/E)-isomers relative to each other were obtained in two stages starting from psoralen: the alkaline solvolysis of psoralen led to furocoumaric acid, which was further Z → E photoisomerized (365 nm) to furocoumarinic acid. The kinetics of Z → E photoisomerization was monitored by HPLC and UV-vis spectrophotometry. Photophysical characteristics in the aqueous phase for both acids, as well as the reversibility of (Z/E) photoisomerization process, were also assessed. Furocoumarinic acid was found to be visibly fluorescent at pH 2.0–12.0, with the maxima of fluorescence emission spectra being pH-dependent. The reverse E → Z photoisomerization predicted by quantum chemistry calculations as energetically favorable for the monoanionic form of furocoumarinic acid was proved in the experiment while being complicated by pyrone ring closure back to psoralen in acidic and neutral conditions. The preparative synthesis of furocoumarinic acid outlined in this work is particularly valuable in view of a wide range of pharmacological effects previously predicted for this compound.

Synthesis of osthol-based botanical fungicides and their antifungal application in crop protection

Plant pathogenic fungi decrease the quality and productivity of plant production. The botanical fungicides have better biocompatibility and rapid biodegradation, little or no cross resistance, and the structural diversity, and thus are beneficial to deal with plant fungal diseases. Osthole has been widely used as the commercial botanical fungicide against powdery mildew in China. In this article, a series of osthole derivatives were synthesized, which respectively contain different substituents on the benzene ring, at the C8-position and pyrone ring. All the target compounds were evaluated in vitro for their antifungal activity against resistant phytopathogenic fungi. Colletotrichum fragariae, Strawberry Botrytis Cinerea, Kiwifruit Botrytis Cinerea, Kiwifruit brown Rots, which are common in fruit fungal diseases. The compound C4 was identified as the most promising candidate with the EC50 values at 38.7 µg/mL against Colletotrichum Fragariae, 14.5 µg/mL against Strawberry Botrytis Cinerea and 24.3 µg/mL against Kiwifruit Botrytis Cinerea, respectively, whereas the antifungal activity against resistant phytopathogenic fungi. of osthole is too low to be used (EC50 > 400 ppm). The results of mycelial relative conductivity determination, PI uptake and fluorescence spectroscopy indicated that the cell membrane of fungi is the key action site of C4. Besides, C4 has the potent inhibitory activity against both of plant and human pathogenic bacteria. Our studies showed that C4 was worthy for further attention as a promising botanical fungicide candidate in crop protection.

Biological Evidences of Dicoumarol: A Review

Dicoumarol, a natural anticoagulant drug chemically designated as is metabolized from Coumarin in the sweet clover (Melilotus alba and Melilotus officinalis) by molds, such as Penicillium nigricans and Penicillium jensi. Coumarin (1,2-benzopyrone), the parent molecule of Dicoumarol, is the simplest compound of a large class of naturally occurring phenolic substances made of fused Benzene and Pyrone rings . In addition, the Coumarin anticoagulants, Dicoumarol (Dicumarol) and its synthetic derivative Warfarin sodium (Coumadin), have been shown to decrease metastases in experimental animals. Warfarin sodium, largely replacing Dicoumarol therapeutically as an anticoagulant, has been used for the treatment of a variety of cancers and shown to improve tumor response rates and survival in patients with several types of cancer. However, despite numerous studies, little information has been acquired on the cellular mechanism of action of Coumarin compounds in the treatment of malignancies. Possibly for this reason, the Coumarin compounds have not received much attention for the treatment of cancer.

Iridium(i) complexes bearing hemilabile coumarin-functionalised N-heterocyclic carbene ligands with application as alkyne hydrosilylation catalysts.

A set of iridium(i) complexes of formula IrCl(κC,η2-IRCouR')(cod) or IrCl(κC, η2-BzIRCouR')(cod) (cod = 1,5-cyclooctadiene; Cou = coumarin; I = imidazolin-2-carbene; BzI = benzimidazolin-2-carbene) have beeen prepared from the corresponding azolium salt and [Ir(μ-OMe)(cod)]2 in THF at room temperature. The crystalline structures of 4b and 5b show a distorted trigonal bipyramidal configuration in the solid state with a coordinated coumarin moiety. In contrast, an equilibrium between this pentacoordinated structure and the related square planar isomer is observed in solution as a consequence of the hemilability of the pyrone ring. Characterization of both species by NMR was achieved at the low and high temperature limits, respectively. In addition, the thermodynamic parameters of the equilibrium, ΔHR and ΔSR, were obtained by VT 1H NMR spectroscopy and fall in the range 22-33 kJ mol-1 and 72-113 J mol-1 K-1, respectively. Carbonylation of IrCl(κC,η2-BzITolCou7,8-Me2)(cod) resulted in the formation of a bis-CO derivative showing no hemilabile behaviour. The newly synthesised complexes efficiently catalyze the hydrosilylation of alkynes at room temperature with a preference for the β-(Z) vinylsilane isomer.

Synthesis, Spectral Studies and Antimicrobial Activity of Coumarin Derivatives

An antimicrobial is a substance that kills or inhibits the growth of microorganisms such as bacteria, fungi, or protozoans. Microorganisms have existed on the earth for more than 3.8 billion years and exhibited the greatest genetic and metabolic diversities. They are an essential component of the biosphere and serve an important role in the maintenance and sustainability of ecosystems. Heterocyclic compounds are cyclic compounds with the ring containing one or more atom other than carbon. The fusion of pyrone ring with benzene nucleus give rise to a class of heterocyclic compound known as benzopyrone, of which two distinct types are recognized: Benzo-α-pyrone commonly called as coumarin. Benzo-γ-pyrone commonly called as chromon. In the present study involves synthesis of substituted 2-((4-methyl-2-oxo-2H-chromen-7-yl)oxy) acetamide derivatives. The synthesized derivatives were evaluated for antibacterial activity using two strains viz. Staphylococcus aureus (MTCC 3160) and Shigella flexneri (MTCC 1457). The synthesized derivatives were also evaluated for antifungal activity using strain Candida albicans (MTCC 227). The antibacterial activity data indicate that certain synthesized derivatives, e.g. derivatives 7a, 7c, 7d and 7e exhibited marked inhibitory activity against the test organisms. The compounds having secondary amines exhibit a very good activity against Gram negative and Gram positive bacteria. The compounds substituted with primary amines had low activity against Gram positive and Gram negative bacteria as compared to secondary amines. The secondary amines possessing bulkier alkyl substitution i.e. diisopropyl had better activity. The antifungal screening results were not encouraging or moderate. Compounds showed very less activity against Candida albicans. The structures of the synthesized compounds were established by IR, NMR and Mass Spectroscopy.

Synthesis and reactivity of 3-(1-alkynyl)chromones

For the first time, the literature data on the methods of synthesis and reactivity of 3-(1-alkynyl)chromones are summarized and systematized. The main method for obtaining these compounds is the Sonogashira cross-coupling reaction of 3-halochromones with terminal acetylenes, and their most important chemical properties include the transformation into furans, reactions with dinucleophiles, ambiphilic [4+2]- and [4+3]-cyclizations, and also dimerization and mixed condensation of 2-methyl-3-(1-alkynyl)chromones due to the vinylogous methyl group. Except for the oxacyclization to furans, chemical transformations of 3-(1-alkynyl)chromones are accompanied by pyrone ring transformation, in which not only the carbonyl group but also the triple bond can participate. This significantly increases the synthetic value of these compounds and ensures the production of more complex heterocyclic systems based on them. The mechanisms of the reactions are discussed, the conditions for their implementation and the yields of the resulting products are indicated.The bibliography includes 80 references.

A Review: Synthesis and Medicinal Importance of Coumarins and their Analogues (Part II)

Coumarins are a set of polyphenolic compounds isolated from plant product tonka bean, coumarou in 1820. They belong to the family of benzopyrones, which includes benzene ring joined with the aid of a pyrone ring. Coumarins have attracted great attention of medicinal chemists and pharmacologists in recent years as they been confirmed to bear diverse pharmacological activities like antiinflammatory and analgesic, anti oxidant, anticancer, etc. This review highlights the method of preparation, chemical reactivity, and organic properties such as anti-inflammatory, anticoagulant, antioxidant, anticancer and analgesic activities, of coumarins and their analogues.

A stereotetrad-centered approach toward pironetin: Dead ends, Detour, and evolution of the synthetic strategy

Pironetin is a unique α-tubulin inhibitor and has been of utmost interest in the synthetic community. Based on the enabling method to access various stereotriads and stereotetrads, we devised a new total synthesis of pironetin, a total 13 steps from commercially available (S)-Roche ester, representing one of the shortest synthetic routes reported to date. The facile fragmentation induced by the deprotonation of the pyrone ring at C4 led us to reorient the installation of the remote enone moiety prior to the lactone ring formation. Moreover, the undesired Michael addition of a phosphate reagent to the acrylate guided us to introduce a sterically demanding cinnamate motif that was also found to facilitate the selective removal of the TBDPS group. The evolution of the synthetic route underlines that the experimental execution of the reactivity of various functional groups is instrumental to devise a successful synthesis.

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral.

The prevention and treatment of obesity is primary based on the follow-up of a healthy lifestyle, which includes a healthy diet with an important presence of bioactive compounds such as polyphenols. For many years, the health benefits of polyphenols have been attributed to their anti-oxidant capacity as free radical scavengers. More recently it has been described that polyphenols activate other cell-signaling pathways that are not related to ROS production but rather involved in metabolic regulation. In this review, we have summarized the current knowledge in this field by focusing on the metabolic effects of flavonoids. Flavonoids are widely distributed in the plant kingdom where they are used for growing and defensing. They are structurally characterized by two benzene rings and a heterocyclic pyrone ring and based on the oxidation and saturation status of the heterocyclic ring flavonoids are grouped in seven different subclasses. The present work is focused on describing the molecular mechanisms underlying the metabolic impact of flavonoids in obesity and obesity-related diseases. We described the effects of each group of flavonoids in liver, white and brown adipose tissue and central nervous system and the metabolic and signaling pathways involved on them.

Synthesis, crystal structure, antiproliferative activity, DNA binding and density functional theory calculations of 3‐(pyridin‐2‐yl)‐8‐tert‐butylcoumarin and its copper(II) complex

A Cu(II)–coumarin complex, [CuL2(NO3)2] (2), where L = 3‐(pyridin‐2‐yl)‐8‐tert‐butylcoumarin (1), was synthesized with Cu(NO3)2⋅3H2O and characterized using elemental, infrared and single‐crystal X‐ray diffraction analyses. The crystal structure of 1 shows that all the pyrone, benzene and pyridine rings are completely coplanar. The crystal structure of 2 is stabilized by intermolecular C–H···O and C–H···N hydrogen bonds and C···C short contacts, which lead to the formation of a two‐dimensional network structure. Density functional theory results give support to the experimentally determined monomeric structure. The in vitro cytotoxic activities of 1 and 2 were investigated against HeLa (cervical carcinoma), A549 (lung), HepG2 (liver) and HUVEC (umbilical vein) cells by MTT assay. The IC50 values show that both 1 and 2 have lower toxicity than doxorubicin and cisplatin in every case. Ligand 1 exhibits higher anti‐HeLa activity than doxorubicin. Complex 2 displays higher anti‐HeLa activity than coumarin but lower than that of cisplatin. Various spectroscopic approaches indicate that 1 and 2 could effectively bind with DNA through intercalation mode.

Pyrone-derived Marine Natural Products: A Review on Isolation, Bio-activities and Synthesis

Marine natural products (MNPs) containing pyrone rings have been isolated from numerous marine organisms, and also produced by marine fungi and bacteria, particularly, actinomycetes. They constitute a versatile structure unit of bioactive natural products that exhibit various biological activities such as antibiotic, antifungal, cytotoxic, neurotoxic, phytotoxic and anti-tyrosinase. The two structure isomers of pyrone ring are γ- pyrone and α-pyrone. In terms of chemical motif, γ-pyrone is the vinologous form of α- pyrone which possesses a lactone ring. Actinomycete bacteria are responsible for the production of several α-pyrone compounds such as elijopyrones A-D, salinipyrones and violapyrones etc. to name a few. A class of pyrone metabolites, polypropionates which have fascinating carbon skeleton, is primarily produced by marine molluscs. Interestingly, some of the pyrone polytketides which are found in cone snails are actually synthesized by actinomycete bacteria. Several pyrone derivatives have been obtained from marine fungi such as Aspergillums flavus, Altenaria sp., etc. The γ-pyrone derivative namely, kojic acid obtained from Aspergillus fungus has high commercial demand and finds various applications. Kojic acid and its derivative displayed inhibition of tyrosinase activity and, it is also extensively used as a ligand in coordination chemistry. Owing to their commercial and biological significance, the synthesis of pyrone containing compounds has been given attention over the past years. Few reviews on the total synthesis of pyrone containing natural products namely, polypropionate metabolites have been reported. However, these reviews skipped other marine pyrone metabolites and also omitted discussion on isolation and detailed biological activities. This review presents a brief account of the isolation of marine metabolites containing a pyrone ring and their reported bio-activities. Further, the review covers the synthesis of marine pyrone metabolites such as cyercene-A, placidenes, onchitriol-I, onchitriol-II, crispatene, photodeoxytrichidione, (-) membrenone-C, lihualide-B, macrocyclic enol ethers and auripyrones-A & B.

Structural Specificity of Flavonoids in the Inhibition of Human Fructose 1,6-Bisphosphatase.

Liver fructose 1,6-bisphosphatase (FBPase) is a recognized regulatory enzyme of the gluconeogenesis pathway, which has emerged as a valid target to control gluconeogenesis-mediated overproduction of glucose. As such, the management of diabetes with FBPase inhibitors represents a potential alternative for the currently used antidiabetic agents. In this study, the FBPase inhibition of a panel of 55 structurally related flavonoids was tested, through a microanalysis screening system. Then, a subset of seven active inhibitors and their close chemical relatives were further evaluated by molecular dynamics (MD) simulations using a linear interaction energy (LIE) approach. The results obtained showed that D14 (herbacetin) was the most potent inhibitor, suggesting that the presence of -OH groups at the C-3, C-4', C-5, C-7, and C-8 positions, as well as the double bond between C-2 and C-3 and the 4-oxo function at the pyrone ring, are favorable for the intended effect. Furthermore, D14 (herbacetin) is stabilized by a strong interaction with the Glu30 side chain and the Thr24 backbone of FBPase. This is the first investigation studying the in vitro inhibitory effect of a panel of flavonoids against human liver FBPase, thus representing a potentially important step for the search and design of novel inhibitors of this enzyme.

Synthesis and Antimicrobial Activity of Some New Coumarin and Dicoumarol Derivatives

Phase transfer catalysis reaction of 4-hydroxy-6-methyl-2H-chromen-2-one with alkyl halides afforded C4 oxygen alkylation products of 2H-chromen-2-one derivatives in appreciative yield, whereas with phenyl isothiocyanate gives the C3 addition product of 4-hydroxy-6-methyl-2-oxo-N-phenyl-2H-chromene-3-carbothioamide, also one pot three component phase transfer reaction was investigated. Treatment of 4-hydroxy-6-methyl-2H-chromen-2-one with aromatic aldehydes in different molar ratios gives 3‑arylidine and the dicoumarol derivatives. However pyrano chromene and pyrano pyridine were obtained by reaction of arylidine with ethyl acetoacetate through Michael cycloaddition reaction. The stability of pyrone ring in 3-arylidine and dicoumarol towards different nucleophilic reagents under reflux and/or fusion conditions has been studied by the action of, hydrazine hydrate, ammonium acetate, methyl amine and p-toluidine afforded compounds 1,2-bis(benzo[d][1,3]dioxol-5-ylmethylene)hydrazine, 1,2-bis(4-methoxybenzylidene)hydrazine and 2,6-bis((2,6-dihydroxy-3-methylphenyl)(hydroxy)methylene)-1-(4-methoxyphenyl)-4-(p-tolyl) piperidine-3,5-dione derivatives. The antimicrobial activity of some synthesized compounds has been investigated.

Synthesis and chemical reactivity of novel pyrano[3,2-c]quinoline-3-carbonitriles

Reaction of 6-methyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde (1) with hydroxylamine hydrochloride under different reaction conditions produced a novel pyrano[3,2-c]quinoline derivatvies 2-5. Ring opening ring closure reactions of pyrano[3,2-c]quinoline-3-carbonitrile 2 with some nitrogen nucleophiles afforded the novel 3-heteroaryl-4-hydroxyquinolines. While, treatment of carbonitrile 3 with some nitrogen nucleohilic reagents produced a diversity of annulated pyrano[3,2-c]quinolines. The chemical reactivity of the prepared pyrano[3,2-c]quinoline-3-carbonitriles 2 and 3 is widely different depending on the different reactivity of pyran-2-one and pyran-4-one moieties toward the nucleophilic reagents as well as the functional groups present in pyrone rings.

Direct Synthesis of 5-Acyl-3-oxy-4-pyrones Based On Acid-­Catalyzed Acylation of Enaminodiones with Acylbenzotriazoles via Soft Enolization

A novel convenient acid-catalyzed acylation of enaminodiones with acylbenzotriazoles via soft enolization has been developed for the direct synthesis of hard-to-reach 5-acyl-3-oxy-4-pyrones. The important advantages of the reaction include broad substrate scope, mild conditions, scalability, and readily isolation of products by crystallization without the use of chromatography. Further modification of the pyrone ring and synthesis of various azaheterocycles via ring-opening transformation have been demonstrated for the preparation of potential scaffolds for inhibition of metalloenzymes.

New data on the reactivity of 2-unsubstituted 3-halochromones

Generalized and systematized information is provided on the chemical properties of 3-halochromones, which can be viewed as geminally activated push-pull haloalkenes. The main focus of this review article is on nucleophilic reactions that can proceed in three different directions with both mono- and bisnucleophiles and can be accompanied by pyrone ring cleavage or preservation. In addition, cycloaddition reactions and metal-catalyzed reactions involving 3-halochromones are described. A total of 56 references are provided.

SYNTHESIS AND SOME CHEMICAL PROPERTIES OF 2-CYANO-4-PYRONE

2-Cyano-4-pyrone obtained from comanic acid ethyl ester reacts with amines and hydrazines with the opening of the pyrone ring and substitution of the cyano group to form carbamoylated aminoenones (yields 62–87%) and pyrazolylacetic acid hydrazides. The reactions of 2-cyano-4-pyrone with hydroxylamine or sodium azide involve exclusively the cyano group, which makes it possible to obtain 2-heteroaryl-4-pyrones and 2-heteroaryl-4-hydroxypyridines. Authors: Dmitrii L. Obydennov*, Aleksandra I. Suslova, Vyacheslav Ya. Sosnovskikh

Synthesis and antimicrobial activity of some new coumarin and dicoumarol derivatives

AbstractPTC reaction of coumarin derivative 1 with alkyl halides afforded C4 oxygen alkylation products 2a‐d in appreciative yield, whereas with phenyl isothiocyanate gives the C3 addition product 4; also, one‐pot three‐component PTC reaction was investigated. Treatment of coumarin 1 with aromatic aldehydes in different molar ratios gives 3‐arylidene derivatives 7a,b and the dicoumarol derivatives 8a,b. Pyrano chromene 9 and pyrano pyridine 10 were obtained by reaction of arylidene 7a with ethyl acetoacetate through Michael cycloaddition reaction. The stability of pyrone ring in 3‐arylidene 7 and dicoumarol 8 towards different nucleophilic reagents under reflux and/or fusion conditions has been studied by the action of hydrazine hydrate, ammonium acetate, methyl amine, and p‐toluidine afforded compounds 11 and 13a‐c. The antimicrobial activity of some synthesized compounds has been investigated.

A profound density functional theory study to unravel the spectroscopic and molecular properties of two Flavanols differing in α‐pyrone ring position

AbstractA comprehensive theoretical model was designed for two new flavanols that have been reported from Glycosmis pentaphylla, differing in the placement of α‐pyrone ring. The density functional theory (DFT) approach was utilized for computing different properties of these compounds to validate the experimental findings and stereochemical assignments. Electronic properties, geometric parameters, frontier molecular orbitals (FMOs), molecular electrostatic potential (MESP), and natural bond orbital analysis were performed for the first time at the PBE0‐D3BJ/def2‐TZVP level of theory for the compounds under study. The simulated vibrational frequencies for compounds 1 and 2 were computed and compared with the experimental results. nuclear magnetic resonance (NMR) (1H and 13C) chemical shift values were computed at the PBE0‐D3BJ/def2‐TZVP/SMDDMSO level of theory and showed a very good agreement with the experimental results for both the compounds. The electronic circular dichroism (ECD) and ultraviolet–visible (UV) spectra for both the compounds were obtained using time‐dependent DFT in methanol, whose results exhibited excellent correlation with experimental data. The intermolecular interaction effect on geometric parameters, vibrational frequencies, and electronic properties were studied for the first time.

3,3′-[(1E,1′E)-Hydrazine-1,2-diylidenebis(ethan-1-yl-1-ylidene)]bis(4-hydroxy-6-methyl-2H-pyran-2-one)

The title compound, C16H16N2O6, lies about an inversion centre at the mid-point of the N—N bond. The molecule features two intramolecular O—H...N and two C—H...O hydrogen bonds, each of which forms an S(6) ring motif. In the crystal, molecules are linked by C—H...O hydrogen bonds into infinite zigzag chains propagating along the c-axis direction. π–π stacking interactions between the pyrone rings [centroid–centroid distances = 3.975 (2) Å] stack the molecules along b.