Showing papers on "Pyran published in 2018"

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study.

Abstract: SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability. The molecular dynamics study examined conformational changes in the enzymes caused by the binding of the substrates and how those changes affected the stability of the protein-drug complex. The average RMSD values of the backbone atoms in compounds 6 and 10 were calculated from 1000 ps to 10000 ps and were found to be 0.13 nm for both compounds. Similarly, the radius of gyration values for compounds 6 and 10 were found to be 1.87 ± 0.03 nm and 1.86 ± 0.02 nm, respectively. The work presented here, will be of great help in lead identification and optimization for early drug discovery.

Enantioselective Construction of Bicyclic Pyran and Hydrindane Scaffolds via Intramolecular Rauhut–Currier Reactions Catalyzed by Thiourea-Phosphines

Abstract: Highly enantioselective intramolecular RC reactions via desymmetrization of cyclohexadienones have been developed. By employing cyclohexadienones with a flexible ether or alkyl group linked internal enone moiety, optically enriched bicyclic pyran and hydrindane skeletons were constructed. Bifunctional phosphine catalysts bearing a thiourea moiety were found to effectively promote the reaction, and preliminary studies suggest that the hydrogen-bonding interaction between thiourea and carbonyl group is crucial and facilitates the otherwise flexible backbones to undergo the desired cyclization.

A novel poly(ethyleneoxide)-based magnetic nanocomposite catalyst for highly efficient multicomponent synthesis of pyran derivatives

Abstract: In the present work, a new magnetically recyclable nanocomposite catalyst was designed, prepared, and characterized by Fourier transform infrared (FT-IR) spectroscopy, field-emission scanning elect...

Highly diastereoselective synthesis of tricyclic fused-pyrans by sequential hydride shift mediated double C(sp3)–H bond functionalization

Abstract: Described herein is the Bronsted acid-catalyzed double C(sp3)–H bond functionalization of alkyl phenethyl ether derivatives. In this process, a [1,5]-[1,5]-hydride shift occurred successively to afford tricyclic fused pyran derivatives in excellent chemical yields with excellent diastereoselectivities (up to >20 : 1). The key to achieve this reaction was the introduction of two methyl groups at the benzylic position, which was effective in both hydride shift processes: (1) the Thorpe–Ingold effect for the first hydride shift and (2) conformational control in the second hydride shift.

Substrate-Controlled Domino Reactions of Crotonate-Derived Sulfur Ylides: Synthesis of Benzothiophene Derivatives.

Abstract: Substrate-controlled domino reactions between thioaurones or their analogues and crotonate-derived sulfur ylides were developed and produced a broad spectrum of benzothiophene-fused pyran derivatives, substituted chromene derivatives. In these reactions, crotonate-derived sulfur ylides acting as two-carbon synthons (α and β carbons or β and γ carbons) in annulation reactions are reported for the first time. These investigations nicely complement and expand previously studied reactions of crotonate-derived sulfur ylides. In addition, reaction mechanisms for these domino reactions are proposed, one of which is supported by DFT calculations.

Anion–cation co-operative catalysis by artificial sweetener saccharine-based ionic liquid for sustainable synthesis of 3,4-dihydropyrano[ c ]chromenes, 4,5-dihydropyrano[4,3- b ]pyran and tetrahydrobenzo[ b ]pyrans in aqueous medium

Abstract: In this study, a saccharine-based ionic liquid [Bmim]Sac has been found to be a sustainable catalyst for the synthesis of 3,4-dihydropyrano[c]chromenes, 4,5-dihydropyrano[4,3-b]pyran and tetrahydrobenzo[b]pyrans scaffolds through Domino Knoevenagel–Michael reaction. The easy recovery of the catalyst and high yield of the products make the protocol attractive, sustainable and economical. A mechanistic hypothesis is discussed using the concept of cooperative catalysis based on the dual (electrophilic/nucleophilic) activation of reactants by [Bmim]Sac. Furthermore, dual hydrogen bonding of saccharinate anions plays an important role in the activation of nucleophiles.

Ferrocene-Containing Ionic Liquid Supported on Silica Nanospheres (SiO2@Imid-Cl@Fc) as a Mild and Efficient Heterogeneous Catalyst for the Synthesis of Pyrano[3,2-b]Pyran Derivatives Under Ultrasound Irradiation:

Abstract: A novel heterogeneous silica nanosphere-supported ferrocene-containing ionic liquid catalyst (SiO2@Imid-Cl@Fc) was designed and synthesised and was systematically characterised by Fourier transform...

Nano titania-supported sulfonic acid (n-TSA) as an efficient, inexpensive, and reusable catalyst for one-pot synthesis of 1, 8-dioxo-octahydroxanthene and tetrahydrobenzo[b]pyran derivatives

Abstract: This paper explains how with the help of nano titania-supported sulfonic acid (n-TSA), new 1,8-dioxo-octahydroxanthene and tetrahydrobenzo[b]pyran derivatives can be produced. To do this, at first n-TSA, which is relatively cheap, easy separable and reusable was made. Next, using this nano catalyst,1,8-dioxo-octahydroxanthene and tetrahydrobenzo[b]pyran derivatives were synthesized from di-ketones and various aromatic aldehydes/or malononitrile without using solvent. Appropriate one-pot operation using different aromatic aldehydes with both electron donating and withdrawing groups have resulted in the best yields. Reusability of the nano catalyst, environmental friendliness, reduced reaction time, non-toxic reaction medium and catalyst high activity are substantial advantages of this work. Nowadays, it is really important that the catalyst can be recovered easily and reused five times while maintaining catalytic activity.

Heterocyclization of polarized system: synthesis, antioxidant and anti-inflammatory 4-(pyridin-3-yl)-6-(thiophen-2-yl) pyrimidine-2-thiol derivatives

Abstract: Chalcones are intent in the daily diet as a favorable chemotherapeutic compound; on the other hand thiophene moiety is present in a large number of bioactive molecules having diverse biological efficiency. Our current goal is the synthesis of (E)-1-(pyridin-3-yl)-3-(thiophen-2-yl) prop-2-en-1-one 3 that’s used as a starting compound to synthesize the novel pyrimidine-2-thiol, pyrazole, pyran derivatives. Chalcones 3 was prepared by condensation of 3-acetylpyridine with thiophene 2-carboxaldehyde which reacted with thiourea to obtain pyrimidinthiol derivative 4. Compound 4 was allowed to react with hydrazine hydrate to afford 2-hydrazinylpyrimidine derivative 5. Compound 5 was used as a key intermediate for a facile synthesis of the targets 6 and 7. In contrast, pyranone 8 was obtained by transformation of compound 5. Using as a precursor for the synthesis of new pyrazolo pyrimidine derivatives 9–10. The major incentive behind the preparation of these compounds was the immense biological activities associated to these heterocyclic derivatives. The newly synthesized compounds (1–4) showed potent anti-inflammatory activities both in vitro and in vivo. They also exhibited promising antioxidant vitalities against α, α-diphenyl-β-picrylhydrazyl scavenging activity and lipid peroxidation. In conclusion, compound 1 showed a hopefully anti-inflammatory and antioxidant activities.

Efficient synthesis of 2-amino-3-cyano-4H-pyran derivatives via a non-catalytic one-pot three-component reaction

Abstract: A convenient one-pot multi-component strategy was conducted successfully under catalyst-free conditions employing water and PEG-400 as the efficient and cheap promoting medium. Three types and nearly 50 2-amino-3-cyano-4H-pyran annulated derivatives were synthesized in good to excellent yields by the condensation of a series of aromatic aldehydes with malononitrile and different 1,3-dicarbonyl compounds. Broad substrate scope, systematic characterization, eliminated catalyst, brief reaction time, and simple purification procedure are the best merits in this process.

Implications of Pyran Cyclization and Pterin Conformation on Oxidized Forms of the Molybdenum Cofactor

Abstract: The large family of mononuclear molybdenum and tungsten enzymes all possess the special ligand molybdopterin (MPT), which consists of a metal-binding dithiolene chelate covalently bound to a pyranopterin group. MPT pyran cyclization/scission processes have been proposed to modulate the reactivity of the metal center during catalysis. We have designed several small-molecule models for the Mo-MPT cofactor that allow detailed investigation into how pyran cyclization modulates electronic communication between the dithiolene and pterin moieties and how this cyclization alters the electronic environment of the molybdenum catalytic site. Using a combination of cyclic voltammetry, vibrational spectroscopy (FT-IR and rR), electronic absorption spectroscopy, and X-ray absorption spectroscopy, distinct changes in the Mo≡O stretching frequency, Mo(V/IV) reduction potential, and electronic structure across the pterin–dithiolene ligand are observed as a function of pyran ring closure. The results are significant, for t...

Structural and Functional Studies of a Pyran Synthase Domain from a trans-Acyltransferase Assembly Line.

Abstract: trans-Acyltransferase assembly lines possess enzymatic domains often not observed in their better characterized cis-acyltransferase counterparts. Within this repertoire of largely unexplored biosynthetic machinery is a class of enzymes called the pyran synthases that catalyze the formation of five- and six-membered cyclic ethers from diverse polyketide chains. The 1.55 A resolution crystal structure of a pyran synthase domain excised from the ninth module of the sorangicin assembly line highlights the similarity of this enzyme to the ubiquitous dehydratase domain and provides insight into the mechanism of ring formation. Functional assays of point mutants reveal the central importance of the active site histidine that is shared with the dehydratases as well as the supporting role of a neighboring semiconserved asparagine.

Total Synthesis of Biselyngbyolide B and Its C21-C22 Z-Isomer.

Abstract: Investigations toward the synthesis of the 18-membered macrolactone biselyngbyolide B (2) from a C1–C13 and a C14–C23 fragment are described. As a key reaction in the synthesis of the C1–C13 fragment, we used an asymmetric propargylation of chiral vinylketene silyl N,O-acetal 12. Access to a C14–C23 fragment featuring a skipped diene and a sensitive allyl alcohol function was initially attempted via reductive fragmentation of a pyran template. However, this ring opening on iodide 32 with t-BuLi led to dienynol 33 with a 21Z double bond. With a silyl protecting group at 3-OH and by implementing an intramolecular Stille coupling for macrolactonization, the 21Z-isomer of biselyngbyolide B (47) was obtained. For preparation of a C14–C23 fragment with the 21E-configuration, a cross-coupling of vinylstannane 48 with 4-bromocrotonate (49) set the configuration of the two double bonds. Biselyngbyolide B (2) was then accessed by an intramolecular Heck coupling. In preliminary biological cytotoxicity assays, 2 turn...

A Metal-Free Approach for the Synthesis of 2-Tetralones via Carbanion-Induced Ring Transformation of 2H-Pyran-2-ones

Abstract: A metal-free, ultrasound-assisted approach for the synthesis of highly functionalized 2-tetralones in high yields is described. The process involves ring transformation of 2H-pyran-2-ones with the spirocyclic ketone 1,4-cyclohexandione monoethylene ketal to yield spiro­cyclic ketals and subsequent acid-mediated hydrolysis. This protocol is free from any organometallic reagents, is economical and tolerates a wide range of functional groups.

Phosphine-catalyzed [4 + 2] annulation of γ-benzyl allenoates: facile synthesis of benzothieno[3,2-b]pyran derivatives.

Abstract: An efficient tris(4-methoxyphenyl)phosphine-catalyzed domino reaction between γ-benzyl allenoates and ethyl (Z)-2-(3-oxobenzo[b]thiophen-2(3H)-ylidene)acetate has been developed, which produces a series of 2H-benzo[4,5]thieno[3,2-b]pyran derivatives in high yields. The substrate scope includes both electron-withdrawing (e.g., halogen) and electron-donating (e.g., methoxy) groups on both the benzothiophene and allenoate moieties. The reaction can also be performed on the gram scale with good yield (e.g., 77%). In this reaction, γ-substituted allenoate acts as a two-carbon synthon, in a manner rarely reported in the literature to date.

Synthesis and characterization of mesoporous silica green catalyst, functionalized with nicotinic acid and its use for synthesis of pyran heterocyclic compounds

Abstract: A simple and convenient method has been used to prepare an SBA-Nicotinic acid (SBA-Niacin) composite on SBA-15 mesoporous silica as support. The composite was easily prepared by nucleophilic substitution of SBA-propylchloride with nicotinic acid. The structural properties of SBA-Niacin were systematically investigated by Fourier transform infrared spectroscopy, scanning electron microscopy, transmission and scanning electron microscopy, X-ray diffraction spectroscopy, thermal gravimetric analysis and Brunauer Emmett Teller. The catalytic activity of this nanocomposite was successfully tested through the one-pot synthesis of pyran annulated heterocyclic compounds via three-component couplings of aromatic aldehydes, malononitrile and β-diketone (dimedone and 4-hydroxy-6-methyl-2-pyrone) under solvent-free conditions.

Expanding the Rubterolone Family: Intrinsic Reactivity and Directed Diversification of PKS-derived Pyrans.

Abstract: We characterized two key biosynthetic intermediates of the intriguing rubterolone family (tropolone alkaloids) that contain a highly reactive pyran moiety (in equilibrium with the hydrolyzed 1,5-dione form) and undergo spontaneous pyridine formation in the presence of primary amines. We exploited the intrinsic reactivity of the pyran moiety and isolated several new rubterolone derivatives, two of which contain a unique thiazolidine moiety. Three rubterolone derivatives were chemically modified with fluorescence and biotin tags using peptide coupling and click reaction. Overall, eight derivatives were fully characterized by HRMS/MS and 1D and 2D NMR spectroscopy and their antimicrobial, cytotoxic, anti-inflammatory and antiparasitic activities evaluated.

Crystal structure of racemic 2-[(β-arabino-pyran-osyl)-sulfanyl]-4,6-diphenylpyridine-3-carbo-nitrile

Abstract: In the racemic title compound, C23H20N2O4S, the sulfur atom is attached equatorially to the sugar ring with unequal S—C bonds, viz.: S—Cs = 1.808 (2) and S—Cp = 1.770 (2) A (s = sugar, p = pyrid­yl). The dihedral angles between the pyridine ring and its attached phenyl groups are 42.24 (8) and 6.37 (14)°. In the crystal, a system of classical O—H⋯O and O—H⋯(O,O) hydrogen bonds links the mol­ecules to form tube-like assemblies propagating parallel to the c-axis direction. Weak C—H⋯N inter­actions are also observed.

One-pot, three-component, selective synthesis of the polyfunctionalized 4H-pyran and 4H-benzo[b]pyran derivatives in the presence of a highly efficient molecular sieve-supported zinc catalyst

Abstract: Abstract A series of pentasubstituted 4H-pyrans and tetrahydrobenzo[b]pyrans are synthesized with excellent yields via a one-pot condensation of aromatic aldehydes, malononitrile, and a dicarbonyl compound, ethyl acetoacetate, acetyl-acetone or dimedone, in the presence of 4 Å molecular sieve modified with zinc(II) as heterogeneous catalyst, in ethanol. The process offers numerous advantages, such as better yield, short reaction time, and mild reaction conditions. The catalyst’s preparation is simple and it could be reused while still maintaining its activity.