Pyrone Moiety Research Articles

Beyond the Bioorthogonal Inverse-Electron-Demand Diels–Alder Reactions of Tetrazines: 2-Pyrone-Functionalized Fluorogenic Probes

AbstractThe applicability of pyrones as a bioorthogonal platform was explored in inverse-electron-demand Diels–Alder (IEDDA) reactions with a strained cyclooctyne. Studies showed that the pyrones are indeed suitable for IEDDA reactions under physiological conditions. Furthermore, the stable pyrone moiety could be utilized to construct easily accessible fluorogenic probes. Mutual orthogonality of the IEDDA reaction of 2-pyrones with SPAAC reactions of azides was also explored.

Comparative Crystallographic Analysis of Some Photoactive Furanocoumarins and Role of C-H…O, C-H…π & π… π Interaction in Their Supramolecular Structure

The compounds taken in this paper to make a comprehensive review are imperatorin, phellopterin, rutaretin, marmesin and bergapten. The aim of this research paper is to confirm the aromatic character of these compounds and to find the different type interactions responsible to assemble the molecules into supramolecular structure. The pyrone moiety of all these molecules is perfectly planar with maximum deviation of 0.009(2) . In all the crystals, molecules are linked by C-H…O hydrogen bonds, forming a three dimensional framework. Different structural motifs (chains, dimmers, rings, etc.) bonded with C-H…π and π…π interactions are analysed, which leads them into supramolecular structures.

Synthesis and Photoswitching Properties of Bioinspired Dissymmetric γ-Pyrone, an Analogue of Cyclocurcumin.

Cyclocurcumin (CC), a turmeric curcuminoid with potential therapeutic properties, is also a natural photoswitch that may undergo E/Z photoisomerization under UV light. To be further exploited in relevant biological applications, photoactivation under near-infrared (NIR) irradiation is required. Such requirement can be met through opportune chemical modifications, by favoring two-photon absorption (TPA) probability. Herein, a general and efficient synthesis of a biomimetic 2,6-disubstituted-γ-pyrone analogue of CC is described, motivated by the fact that molecular modeling previews an order of magnitude increase of its NIR TPA compared to CC. Three retrosynthetic pathways have been identified (i) via an aryl-oxazole intermediate or via aryl-diynone through (ii) a bottom-up or (iii) a top-down approach. While avoiding the passage through unstable synthons or low-yield intermediate reactions, only the latest approach could conveniently afford the 2,6-disubstituted-γ-pyrone analogue of CC, in ten steps and with an overall yield of 18%. The photophysical properties of our biomimetic analogue have also been characterized showing an improved photoisomerization yield over the parent natural compound. The potentially improved nonlinear optical properties, as well as enhanced stability, may be correlated to the enforcement of the planarity of the pyrone moiety leading to a quadrupolar D-π-A-π-D system.

Synthetic Routes to Coumarin(Benzopyrone)-Fused Five-Membered Aromatic Heterocycles Built on the α-Pyrone Moiety. Part 1: Five-Membered Aromatic Rings with One Heteroatom.

This review gives an up-to-date overview of the different ways (routes) to the synthesis of coumarin(benzopyrone)-fused, five-membered aromatic heterocycles with one heteroatom, built on the pyrone moiety. Covering 1966 to 2020.

Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran

AbstractAn unprecedented deconstructive reorganization strategy for the de novo synthesis of hydroxylated benzofurans from kojic acid‐ or maltol‐derived alkynes is reported. In this reaction, both the benzene and furan rings were simultaneously constructed, whereas the pyrone moiety of the kojic acid or maltol was deconstructed and then reorganized into the benzene ring as a six‐carbon component. Through this strategy, at least one free hydroxyl group was introduced into the benzene ring in a substitution‐pattern tunable fashion without protection–deprotection and redox adjustment. With this method, a large number of hydroxylated benzofuran derivatives with different substitution‐patterns have been prepared efficiently. This methodology has also been shown as the key step in a collective total synthesis of hydroxylated benzofuran‐containing natural products (11 examples).

Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran.

An unprecedented deconstructive reorganization strategy for the de novo synthesis of hydroxylated benzofurans from kojic acid- or maltol-derived alkynes is reported. In this reaction, both the benzene and furan rings were simultaneously constructed, whereas the pyrone moiety of the kojic acid or maltol was deconstructed and then reorganized into the benzene ring as a six-carbon component. Through this strategy, at least one free hydroxyl group was introduced into the benzene ring in a substitution-pattern tunable fashion without protection-deprotection and redox adjustment. With this method, a large number of hydroxylated benzofuran derivatives with different substitution-patterns have been prepared efficiently. This methodology has also been shown as the key step in a collective total synthesis of hydroxylated benzofuran-containing natural products (11 examples).

Molecular structure of a tolyl derivative of γ-pyrone

A study of the molecular structure of a new derivative of γ-pyrone, which is assumed to be of biological and pharmacological importance, has been carried out. The detailed insight into the structure of the γ-pyrone derivative was obtained by 1H NMR, 13C NMR, IR and Raman spectroscopy. Furthermore, its crystal structure was determined by single crystal X-ray diffraction method and its behavior in solutions was examined by UV/Vis and fluorescence spectroscopy. Assignment of the vibrational spectra of the studied compound is presented and correlated to some structural parameters. DFT calculations, namely geometry optimization, frequency calculations, and NBO population analysis, were performed at B3LYP/6-311G++(d,p) level of theory and the obtained data was compared to the experimental results to further elucidate the structural details. In addition, energies of the electronic transitions were estimated using DFT calculations at the same level of theory, and the calculated results showed good agreement with experimental data. It was shown that longer CC and shorter CC bonds alternate in the pyrone ring and that the structure of the studied γ-pyrone derivative comprises two intramolecular CH⋯O bonds. All the results pointed to relatively weak π-electron delocalization inside the pyrone moiety and significantly stronger π-electron delocalization through tolyl substituents.

New insights into the antioxidant activity and cytotoxicity of arzanol and effect of methylation on its biological properties

The heterodimeric phloroglucinyl pyrone arzanol (Arz) has raised considerable interest because of its antiviral, anti-inflammatory, and antioxidant activity. We have investigated the effect of methylation of the pyrone moiety on the antioxidant activity and cytotoxicity of Arz. This manoeuvre, that left the polyphenolic moiety unscathed, was nevertheless detrimental for antioxidant activity in both the cholesterol thermal degradation- and the Cu2+-induced liposome oxidation assays, providing evidence of structure-activity relationships that go beyond the preservation of the polyphenolic pharmacophore. The antioxidant activity of Arz was retained also in the Fe-NTA model of in vivo oxidative stress, with protective effect on the oxidative degradation of plasmatic lipids, unsaturated fatty acids and cholesterol. Both Arz and methylarzanol (Me-Arz) were devoid of toxic effect on colonic differentiated Caco-2 cells up to 100μM, but significantly reduced cancer Caco-2 cell viability at lower dosages. Arz could also selectively reduce viability of other cancer cell lines, [murine melanoma cells (B16F10 cells), human cervical carcinoma cells (HeLa cells)], suggesting that it can act as a selective modulator of cell processes typical of cancer cells. Taken together, our results qualify Arz as a lead structure for further in vivo investigation of its pharmacological potential.

ChemInform Abstract: Palladium‐Catalyzed Double‐Decarboxylative Addition to Pyrones: Synthesis of Conjugated Dienoic Esters.

An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct.

Palladium-Catalyzed Double-Decarboxylative Addition to Pyrones: Synthesis of Conjugated Dienoic Esters.

An interceptive decarboxylative allylation protocol has been developed utilizing pyrone as a C4 synthon. This palladium-catalyzed transformation difunctionalizes the pyrone moiety by in situ generation and activation of both the electrophile and nucleophile via a double decarboxylation pathway. Ultimately, allyl carbonates react smoothly with 2-carboxypyrone under mild reaction conditions to generate synthetically useful acyclic dienoic esters, forming carbon dioxide as the sole byproduct.

ChemInform Abstract: Total Synthesis of Diterpenoid Pyrones, Nalanthalide, Sesquicillin, Candelalides A‐C, and Subglutinols A, B

AbstractReview: 36 refs.

Synthesis and Antimicrobial Activity Evaluation of Novel 4-Thiazolidinones Containing a Pyrone Moiety

A series of thiosemicarbazones 3a–d and 4-thiazolidinones 5a–d, 7a–d, and 9a–h were synthesized and evaluated for their in vitro antimicrobial activity. Condensation of 3-acetyl-4-hydroxy-6-methyl-2H pyran-2-one1 (dehydroacetic acid) with thiosemicarbazide 2a–d in ethanol at room temperature yielded the thiosemicarbazones 3a–d. These compounds were exploited to synthesize the 4-thiazolidinones 5a–d via their reactions with ethyl 2-bromo propionate4. Derivatives 7a–d were prepared by reaction of the thiosemicarbazones 3a–d with phenyl bromoacetate 6. The 4-thiazolidinones 9a–h were obtained by treatment of compound 3a or 3c with maleimide derivatives 8a–d in refluxing ethanol, under sulfuric acid catalysis. All compounds were screened in vitro for their antibacterial and antifungal activities against five human pathogens microorganisms: Escherichia coli ATCC 25992, Pseudomonas aeruginosa ATCC 27852, Staphylococcus aureus ATCC 43300, Staphylococcus aureus ATCC 25923, and Candida albicans.

Electronic structure and photoreactivity of the triplet states of skin-sensitizing psoralens

The photoreactive states of skin-sensitizing-carcinogenic psoralens (furocoumarins) are characterized by the configuration analysis method of Baba and coworkers. The S1 (π, π*) states of coumarin and psoralen possess significant charge transfer (CT) character in the CC bond of the pyrone moiety (32% CT to the CC vacant orbital in coumarin and 22% in psoralen) and in the CC bond of the furyl moiety (4% CT to the vacant CC orbital and 14% CT from the occupied CC orbital in psoralen). On the other hand, the T1, (π, π*) state of these molecules shows a substantial localization of the excitation in the pyrone CC bond, thus providing a logical basis for the structure-activity correlation of skin-sensitizing coumarins.

Phenylnannolones A–C: Biosynthesis of New Secondary Metabolites from the Myxobacterium Nannocystis exedens

Myxobacteria are gliding bacteria that belong to the delta-Proteobacteria and are known for their unique biosynthetic capabilities. Among myxobacteria, Nannocystis spp. are most closely related to marine myxobacteria and their secondary metabolism has hardly been investigated. Phenylnannolones A (1), B (2) and C (3) were obtained from a culture of Nannocystis exedens that was isolated from the intertidal region of Crete. Compound 1 had inhibitory activity toward the ABCB1 gene product P-glycoprotein and reversed daunorubicin resistance in cultured cancer cells. Phenylnannolone A has an unusual structural architecture; it is composed of an ethyl-substituted polyene chain linked to a pyrone moiety on one side and to a phenyl ring on the other. The investigation of the biosynthesis with labelled precursors revealed acetate, butyrate and phenylalanine as building blocks for 1. The labelling pattern suggested novel biochemical reactions for the biosynthesis of the starter unit.

Synthesis of some new 1-aryl-4-formyl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)pyrazoles using the Vilsmeier–Haack reaction — Isolation of the key intermediate 1-aryl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)pyrazoles

Arylhydrazones of dehydroacetic acid (DHA) underwent Vilsmeier–Haack reaction to generate the corresponding 1-aryl-4-formyl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)pyrazoles (1) with the pyrone moiety of the DHA remaining intact. However, when the reaction was performed using 1 equiv. of the reagent, compounds of 1-aryl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)pyrazoles (2a–2f) were obtained, which underwent smooth conversion to 1-aryl-4-formyl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)pyrazoles (1) on further treatment with another equivalent of the Vilsmeier–Haack reagent. This unreported observation suggests the intermediacy of 1-aryl-3-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)pyrazoles (2) in Vilsmeier–Haack reactions of hydrazones with a pyrone moiety. Several analogous compounds were also prepared using arylhydrazones of DHA.Key words: dehydroacetic acid, pyrazoles, Vilsmeier–Haack reaction, 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one.

The Synthesis of Deoxyfusapyrone. Part 2. Preparation of the Bis‐Trisubstituted Olefin Fragment and Its Attachment to the Pyrone Moiety.

The Synthesis of Deoxyfusapyrone. Part 2. Preparation of the Bis‐Trisubstituted Olefin Fragment and Its Attachment to the Pyrone Moiety.

Synthesis of (.+‐.)‐Solanapyrones A and B.

AbstractFor Abstract see ChemInform Abstract in Full Text.

The synthesis of deoxyfusapyrone. 2. Preparation of the bis-trisubstituted olefin fragment and its attachment to the pyrone moiety.

A convergent and modular synthesis has been devised to construct the eight diastereoisomers of deoxyfusapyrone (1). In this paper the synthesis of the complex polyene chain is reported as is its connection to the pyrone moiety that is in the middle of the structure of the final target molecule. This route has been fully worked out for one of the isomers and will now be applied in a parallel synthesis format to make all the stereoisomers of 1.

Synthesis of (±)-solanapyrones A and B

In this paper we report the development of a stereoselective IMDA approach to the phytotoxic polyketides (±)-solanapyrones A and B. The stereoselectivity of the key IMDA cycloaddition was optimized by investigating a range of 2,8,10-dodecatrienoic acid derivatives. This established that use of the Weinreb amide led to the desired exo-selectivity and also facilitated construction of the pyrone moiety. A novel approach to the installation of the C-3 formyl group in solanapyrone A is also described.

The synthesis of deoxyfusapyrone. 1. An approach to the pyrone moiety.

An effective synthesis of the C1-C10 component of deoxyfusapyrone has been achieved that will allow for the synthesis of both the (R) and (S) form of the C-8 chiral center starting from optically pure (+)- and (-)-3,3-dimethyl-2-hydroxy-gammalactone (pantolactone).