Sample records for tetrahydropyran


    Tetrahydropyrans are integral moieties in innumerable natural products and have inspired the development of a variety of different methodologies. A Prins-type cyclization involving the coupling of a homoallylic alcohol and an aldehyde in the presence of catalytic scandium triflat...

  2. Theoretical study of the reaction kinetics of atomic bromine with tetrahydropyran

    KAUST Repository

    Giri, Binod; Lo, John M H; Roscoe, John M.; Alquaity, Awad; Farooq, Aamir


    A detailed theoretical analysis of the reaction of atomic bromine with tetrahydropyran (THP, C5H10O) was performed using several ab initio methods and statistical rate theory calculations. Initial geometries of all species involved in the potential

  3. Diastereoselective synthesis of tetrahydropyrans via Prins-Ritter and Prins-arylthiolation cyclization reactions. (United States)

    Hazarika, Nabajyoti; Sarmah, Barnali; Bordoloi, Manobjyoti; Phukan, Prodeep; Baishya, Gakul


    An efficient method has been developed for the synthesis of two new classes of tetrahydropyran derivatives comprising amide, tetrazole or benzothiazole moieties via a three-component reaction of 6-methylhept-5-en-2-ol, arylaldehydes and nitriles/thiols in the presence of a tetrafluoroboric acid diethyl ether complex. The reaction proceeds via the formation of an oxocarbenium ion. This protocol is highly diastereoselective and only single diastereomer has been isolated in each case.

  4. Synthesis and Anticancer Activities of Novel Guanylhydrazone and Aminoguanidine Tetrahydropyran Derivatives. (United States)

    Silva, Fábio Pedrosa Lins; Dantas, Bruna Braga; Faheina Martins, Gláucia Veríssimo; de Araújo, Demétrius Antônio Machado; Vasconcellos, Mário Luiz Araújo de Almeida


    In this paper we present the convenient syntheses of six new guanylhydrazone and aminoguanidine tetrahydropyran derivatives 2-7. The guanylhydrazone 2, 3 and 4 were prepared in 100% yield, starting from corresponding aromatic ketones 8a-c and aminoguanidine hydrochloride accessed by microwave irradiation. The aminoguanidine 5, 6 and 7 were prepared by reduction of guanylhydrazone 2-4 with sodium cyanoborohydride (94% yield of 5, and 100% yield of 6 and 7). The aromatic ketones 8a-c were prepared from the Barbier reaction followed by the Prins cyclization reaction (two steps, 63%-65% and 95%-98%). Cytotoxicity studies have demonstrated the effects of compounds 2-7 in various cancer and normal cell lines. That way, we showed that these compounds decreased cell viabilities in a micromolar range, and from all the compounds tested we can state that, at least, compound 3 can be considered a promising molecule for target-directed drug design.

  5. Dynamical (e,2e) studies of tetrahydropyran and 1,4-dioxane

    Energy Technology Data Exchange (ETDEWEB)

    Builth-Williams, J. D.; Chiari, L.; Jones, D. B., E-mail:, E-mail: [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Silva, G. B. da [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Universidade Federal de Mato Grosso, Barra do Garças, MT 78600-000 (Brazil); Chaluvadi, Hari; Madison, D. H. [Department of Physics, Missouri University of Science and Technology, Rolla, Missouri 65409 (United States); Brunger, M. J., E-mail:, E-mail: [School of Chemical and Physical Sciences, Flinders University, GPO Box 2100, Adelaide, South Australia 5001 (Australia); Institute of Mathematical Sciences, University of Malaya, 50603 Kuala Lumpur (Malaysia)


    We present experimental and theoretical results for the electron-impact ionization of the highest occupied molecular orbitals of tetrahydropyran and 1,4-dioxane. Using an (e,2e) technique in asymmetric coplanar kinematics, angular distributions of the slow ejected electron, with an energy of 20 eV, are measured when incident electrons at 250 eV ionize the target and scatter through an angle of either −10° or −15°. The data are compared with calculations performed at the molecular 3-body distorted wave level. Fair agreement between the theoretical model and the experimental measurements was observed. The similar structures for these targets provide key insights for assessing the limitations of the theoretical calculations. This study in turn facilitates an improved understanding of the dynamics in the ionization process.

  6. Theoretical study of the reaction kinetics of atomic bromine with tetrahydropyran

    KAUST Repository

    Giri, Binod


    A detailed theoretical analysis of the reaction of atomic bromine with tetrahydropyran (THP, C5H10O) was performed using several ab initio methods and statistical rate theory calculations. Initial geometries of all species involved in the potential energy surface of the title reaction were obtained at the B3LYP/cc-pVTZ level of theory. These molecular geometries were reoptimized using three different meta-generalized gradient approximation (meta-GGA) functionals. Single-point energies of the stationary points were obtained by employing the coupled-cluster with single and double excitations (CCSD) and fourth-order Møller-Plesset (MP4 SDQ) levels of theory. The computed CCSD and MP4(SDQ) energies for optimized structures at various DFT functionals were found to be consistent within 2 kJ mol-1. For a more accurate energetic description, single-point calculations at the CCSD(T)/CBS level of theory were performed for the minimum structures and transition states optimized at the B3LYP/cc-pVTZ level of theory. Similar to other ether + Br reactions, it was found that the tetrahydropyran + Br reaction proceeds in an overall endothermic addition-elimination mechanism via a number of intermediates. However, the reactivity of various ethers with atomic bromine was found to vary substantially. In contrast with the 1,4-dioxane + Br reaction, the chair form of the addition complex (c-C5H10O-Br) for THP + Br does not need to undergo ring inversion to form a boat conformer (b-C4H8O2-Br) before the intramolecular H-shift can occur to eventually release HBr. Instead, a direct, yet more favorable route was mapped out on the potential energy surface of the THP + Br reaction. The rate coefficients for all relevant steps involved in the reaction mechanism were computed using the energetics of coupled cluster calculations. On the basis of the results of the CCSD(T)/CBS//B3LYP/cc-pVTZ level of theory, the calculated overall rate coefficients can be expressed as kov.,calc.(T) = 4.60 × 10

  7. Synthesis and Anticancer Activities of Novel Guanylhydrazone and Aminoguanidine Tetrahydropyran Derivatives

    Directory of Open Access Journals (Sweden)

    Fábio Pedrosa Lins Silva


    Full Text Available In this paper we present the convenient syntheses of six new guanylhydrazone and aminoguanidine tetrahydropyran derivatives 2–7. The guanylhydrazone 2, 3 and 4 were prepared in 100% yield, starting from corresponding aromatic ketones 8a–c and aminoguanidine hydrochloride accessed by microwave irradiation. The aminoguanidine 5, 6 and 7 were prepared by reduction of guanylhydrazone 2–4 with sodium cyanoborohydride (94% yield of 5, and 100% yield of 6 and 7. The aromatic ketones 8a–c were prepared from the Barbier reaction followed by the Prins cyclization reaction (two steps, 63%–65% and 95%–98%. Cytotoxicity studies have demonstrated the effects of compounds 2–7 in various cancer and normal cell lines. That way, we showed that these compounds decreased cell viabilities in a micromolar range, and from all the compounds tested we can state that, at least, compound 3 can be considered a promising molecule for target-directed drug design.

  8. Synthesis of carboxylic acids, esters, alcohols and ethers containing a tetrahydropyran ring derived from 6-methyl-5-hepten-2-one. (United States)

    Hanzawa, Yohko; Hashimoto, Kahoko; Kasashima, Yoshio; Takahashi, Yoshiko; Mino, Takashi; Sakamoto, Masami; Fujita, Tsutomu


    3-hydroxy acids, 3-hydroxy-3,7-dimethyloct-6-enoic acid (1) and 3-hydroxy-2,2,3,7-tetramethyloct-6-enoic acid (2), were prepared from 6-methyl-5-hepten-2-one, and they were subsequently used to prepare (2,6,6-trimethyltetrahydropyran-2-yl)acetic acid (3) and 2-methyl-2-(2,6,6-trimethyltetrahydropyran-2-yl)propanoic acid (4), respectively, via cyclization with an acidic catalyst such as boron trifluoride diethyl etherate or iodine. The reaction of carboxylic acids 3 and 4 with alcohols, including methanol, ethanol, and 1-propanol, produced the corresponding methyl, ethyl, and propyl esters, which all contained a tetrahydropyran ring. Reduction of carboxylic acids 3 and 4 afforded the corresponding alcohols. Subsequent reactions of these alcohols with several acyl chlorides produced novel esters. The alcohols also reacted with methyl iodide and sodium hydride to provide novel ethers. A one-pot cyclization-esterification of 1 to produce esters containing a tetrahydropyran ring, using iodine as a catalyst, was also investigated.

  9. Synthesis of 2,6-trans- and 3,3,6-trisubstituted tetrahydropyran-4-ones from Maitland-Japp derived 2H-dihydropyran-4-ones: a total synthesis of diospongin B. (United States)

    Clarke, Paul A; Nasir, Nadiah Mad; Sellars, Philip B; Peter, Alejandra M; Lawson, Connor A; Burroughs, James L


    6-Substituted-2H-dihydropyran-4-one products of the Maitland-Japp reaction have been converted into tetrahydropyrans containing uncommon substitution patterns. Treatment of 6-substituted-2H-dihydropyran-4-ones with carbon nucleophiles led to the formation of tetrahydropyran rings with the 2,6-trans-stereochemical arrangement. Reaction of the same 6-substituted-2H-dihydropyran-4-ones with l-Selectride led to the formation of 3,6-disubstituted tetrahydropyran rings, while trapping of the intermediate enolate with carbon electrophiles in turn led to the formation 3,3,6-trisubstituted tetrahydropyran rings. The relative stereochemical configuration of the new substituents was controlled by the stereoelectronic preference for pseudo-axial addition of the nucleophile and trapping of the enolate from the opposite face. Application of these methods led to a synthesis of the potent anti-osteoporotic diarylheptanoid natural product diospongin B.

  10. (Vapour + liquid) equilibria for binary and ternary mixtures of 2-propanol, tetrahydropyran, and 2,2,4-trimethylpentane at P = 101.3 kPa

    International Nuclear Information System (INIS)

    Lin, Dun-Yi; Tu, Chein-Hsiun


    Highlights: ► We report the VLE data at P = 101.3 kPa involving a cyclic ether. ► The activity coefficients of mixtures were obtained from modified Raoult’s law. ► The VLE data were correlated by four liquid activity coefficient models. ► The ternary VLE data were predicted from binary parameters of the four models. - Abstract: (Vapour + liquid) equilibrium (VLE) at P = 101.3 kPa have been determined for a ternary system (2-propanol + tetrahydropyran + 2,2,4-trimethylpentane) and its constituent binary systems (2-propanol + tetrahydropyran, 2-propanol + 2,2,4-trimethylpentane), and (tetrahydropyran + 2,2,4-trimethylpentane). Analysis of VLE data reveals that two binary systems (2-propanol + tetrahydropyran) and (2-propanol + 2,2,4-trimethylpentane) have a minimum boiling azeotrope. No azeotrope was found for the ternary system. The activity coefficients of liquid mixtures were obtained from the modified Raoult’s law and were used to calculate the reduced excess molar Gibbs free energy (g E /RT). Thermodynamic consistency tests were performed for all VLE data using the Van Ness direct test for the binary systems and the test of McDermott–Ellis as modified by Wisniak and Tamir for the ternary system. The VLE data of the binary mixtures were correlated using the three-suffix Margules, Wilson, NRTL, and UNIQUAC activity-coefficient models. The models with their best-fitted interaction parameters of the binary systems were used to predict the ternary (vapour + liquid) equilibrium.

  11. Effect of double bonds on the conducting properties of ciguatoxin 3C and tetrahydropyrane-based polymers: a theoretical study. (United States)

    Matus, Myrna H; Garza, Jorge; Galván, Marcelo


    The electronic structure of the ciguatoxin 3C is analyzed through the Kohn-Sham model by using two different kinds of basis sets: localized basis set (Gaussian functions) and nonlocalized basis set (plane wave functions). With the localized basis functions, two approximations are used for the exchange-correlation functional: the local density approximation and the generalized gradient approximation. With the nonlocalized basis set, just the local density approximation is used. The energy gap, obtained from the frontier molecular orbitals, for this molecule predicts that this system is a semiconductor, even when the number of double bonds is increased inside the structure. However, as large molecules built with the basic unit--the tetrahydropyrane--of the ciguatoxin 3C are found in nature, it suggests studying the gap in polymeric systems built with the basic unit of this molecule. It is demonstrated that the presence of double bonds reduces considerably the gap, indicating the possibility of forming conducting materials by introducing double bonds in this kind of molecular systems. Thus, molecules strongly linked with biological systems can be used as precursor to build electric conducting systems.

  12. Synthesis of Tetrahydropyran from Tetrahydrofurfuryl Alcohol over Cu–Zno/Al2O3 under a Gaseous-Phase Condition

    Directory of Open Access Journals (Sweden)

    Fengyuan Zhang


    Full Text Available Tetrahydropyran (THP represents an O-containing hetero-cyclic compound that can be used as a promising solvent or monomer for polymer synthesis. In this work, Cu–ZnO/Al2O3 catalysts have been prepared by a facile precipitation–extrusion method and used for the synthesis of THP through gaseous-phase hydrogenolysis of tetrahydrofurfuryl alcohol (THFA. The effect of the molar ratio of Cu/Zn/Al, reaction temperature, and hydrogen pressure was investigated. An 89.4% selectivity of THP was achieved at 270 °C and 1.0 MPa H2. Meanwhile, the optimum molar ratio of Cu/Zn/Al was determined to be 4:1:10. The Cu–ZnO/Al2O3 catalyst exhibited high catalytic activity and stability for 205 h on-stream. A possible reaction mechanism involving several consecutive reactions was proposed: THFA was firstly rearranged to 2-hydroxytetrahydropyran (2-HTHP, followed by the dehydration of 2-HTHP to 3,4-2H-dihydropyran (DHP over acid sites; finally, the DHP was hydrogenated to THP. The synergy of acid sites and metal sites of Cu–ZnO/Al2O3 played an important role during the production of THP.

  13. Thermodynamic properties of binary mixtures of tetrahydropyran with pyridine and isomeric picolines: Excess molar volumes, excess molar enthalpies and excess isentropic compressibilities

    International Nuclear Information System (INIS)

    Saini, Neeti; Jangra, Sunil K.; Yadav, J.S.; Sharma, Dimple; Sharma, V.K.


    Research highlights: → Densities, ρ and speeds of sound, u of tetrahydropyran (i) + pyridine or α-, β- or γ-picoline (j) binary mixtures at 298.15, 303.15 and 308.15 K and excess molar enthalpies, H E of the same set of mixtures at 308.15 K have been measured as a function of composition. → The observed densities and speeds of sound values have been employed to determine excess molar volumes, V E and excess isentropic compressibilities, κ S E . → Topology of the constituents of mixtures has been utilized (Graph theory) successfully to predict V E , H E and κ S E data of the investigated mixtures. → Thermodynamic data of the various mixtures have also been analyzed in terms of Prigogine-Flory-Patterson (PFP) theory. - Abstract: Densities, ρ and speeds of sound, u of tetrahydropyran (i) + pyridine or α-, β- or γ- picoline (j) binary mixtures at 298.15, 303.15 and 308.15 K and excess molar enthalpies, H E of the same set of mixtures at 308.15 K have been measured as a function of composition using an anton Parr vibrating-tube digital density and sound analyzer (model DSA 5000) and 2-drop micro-calorimeter, respectively. The resulting density and speed of sound data of the investigated mixtures have been utilized to predict excess molar volumes, V E and excess isentropic compressibilities, κ S E . The observed data have been analyzed in terms of (i) Graph theory; (ii) Prigogine-Flory-Patterson theory. It has been observed that V E , H E and κ S E data predicted by Graph theory compare well with their experimental values.

  14. Three-dimensional quantitative structure-activity relationship (3D QSAR) and pharmacophore elucidation of tetrahydropyran derivatives as serotonin and norepinephrine transporter inhibitors (United States)

    Kharkar, Prashant S.; Reith, Maarten E. A.; Dutta, Aloke K.


    Three-dimensional quantitative structure-activity relationship (3D QSAR) using comparative molecular field analysis (CoMFA) was performed on a series of substituted tetrahydropyran (THP) derivatives possessing serotonin (SERT) and norepinephrine (NET) transporter inhibitory activities. The study aimed to rationalize the potency of these inhibitors for SERT and NET as well as the observed selectivity differences for NET over SERT. The dataset consisted of 29 molecules, of which 23 molecules were used as the training set for deriving CoMFA models for SERT and NET uptake inhibitory activities. Superimpositions were performed using atom-based fitting and 3-point pharmacophore-based alignment. Two charge calculation methods, Gasteiger-Hückel and semiempirical PM3, were tried. Both alignment methods were analyzed in terms of their predictive abilities and produced comparable results with high internal and external predictivities. The models obtained using the 3-point pharmacophore-based alignment outperformed the models with atom-based fitting in terms of relevant statistics and interpretability of the generated contour maps. Steric fields dominated electrostatic fields in terms of contribution. The selectivity analysis (NET over SERT), though yielded models with good internal predictivity, showed very poor external test set predictions. The analysis was repeated with 24 molecules after systematically excluding so-called outliers (5 out of 29) from the model derivation process. The resulting CoMFA model using the atom-based fitting exhibited good statistics and was able to explain most of the selectivity (NET over SERT)-discriminating factors. The presence of -OH substituent on the THP ring was found to be one of the most important factors governing the NET selectivity over SERT. Thus, a 4-point NET-selective pharmacophore, after introducing this newly found H-bond donor/acceptor feature in addition to the initial 3-point pharmacophore, was proposed.

  15. The C-2 derivatives of salvinorin A, ethoxymethyl ether Sal B and β-tetrahydropyran Sal B, have anti-cocaine properties with minimal side effects. (United States)

    Ewald, Amy W M; Bosch, Peter J; Culverhouse, Aimee; Crowley, Rachel Saylor; Neuenswander, Benjamin; Prisinzano, Thomas E; Kivell, Bronwyn M


    Kappa-opioid receptor (KOPr) agonists have pre-clinical anti-cocaine and analgesic effects. However, side effects including sedation, dysphoria, aversion, anxiety and depression limit their therapeutic development. The unique structure of salvinorin A has been used to develop longer acting KOPr agonists. We evaluate two novel C-2 analogues of salvinorin A, ethoxymethyl ether Sal B (EOM Sal B) and β-tetrahydropyran Sal B (β-THP Sal B) alongside U50,488 for their ability to modulate cocaine-induced behaviours and side effects, pre-clinically. Anti-cocaine properties of EOM Sal B were evaluated using the reinstatement model of drug seeking in self-administering rats. EOM Sal B and β-THP Sal B were evaluated for effects on cocaine-induced hyperactivity, spontaneous locomotor activity and sucrose self-administration. EOM Sal B and β-THP Sal B were evaluated for aversive, anxiogenic and depressive-like effects using conditioned place aversion (CPA), elevated plus maze (EPM) and forced swim tests (FSTs), respectively. EOM Sal B (0.1, 0.3 mg/kg, intraperitoneally (i.p.)) dose dependently attenuated drug seeking, and EOM Sal B (0.1 mg/kg, i.p.) and β-THP Sal B (1 mg/kg, i.p.) attenuated cocaine-induced hyperactivity. No effects on locomotor activity, open arm times (EPM) or swimming behaviours (FST) were seen with EOM (0.1 or 0.3 mg/kg, i.p.) or β-THP Sal B (1 or 2 mg/kg, i.p.). However, β-THP Sal B decreased time spent in the drug-paired chamber. EOM Sal B is more potent than Sal A and β-THP Sal B in reducing drug-seeking behaviour with fewer side effects. EOM Sal B showed no effects on sucrose self-administration (0.1 mg/kg), locomotor, depressive-like, aversive-like or anxiolytic effects.

  16. Evolution of the Petasis-Ferrier union/rearrangement tactic: construction of architecturally complex natural products possessing the ubiquitous cis-2,6-substituted tetrahydropyran structural element. (United States)

    Smith, Amos B; Fox, Richard J; Razler, Thomas M


    The frequent low abundance of architecturally complex natural products possessing significant bioregulatory properties mandates the development of rapid, efficient, and stereocontrolled synthetic tactics, not only to provide access to the biologically rare target but also to enable elaboration of analogues for the development of new therapeutic agents with improved activities and/or pharmacokinetic properties. In this Account, the genesis and evolution of the Petasis-Ferrier union/rearrangement tactic, in the context of natural product total syntheses, is described. The reaction sequence comprises a powerful tactic for the construction of the 2,6- cis-substituted tetrahydropyran ring system, a ubiquitous structural element often found in complex natural products possessing significant bioactivities. The three-step sequence, developed in our laboratory, extends two independent methods introduced by Ferrier and Petasis and now comprises: condensation between a chiral, nonracemic beta-hydroxy acid and an aldehyde to furnish a dioxanone; carbonyl olefination; and Lewis-acid-induced rearrangement of the resultant enol acetal to generate the 2,6- cis-substituted tetrahydropyranone system in a highly stereocontrolled fashion. To demonstrate the envisioned versatility and robustness of the Petasis-Ferrier union/rearrangement tactic in complex molecule synthesis, we exploited the method as the cornerstone in our now successful total syntheses of (+)-phorboxazole A, (+)-zampanolide, (+)-dactylolide, (+)-spongistatins 1 and 2, (-)-kendomycin, (-)-clavosolide A, and most recently, (-)-okilactomycin. Although each target comprises a number of synthetic challenges, this Account focuses on the motivation, excitement, and frustrations associated with the evolution and implementation of the Petasis-Ferrier union/rearrangement tactic. For example, during our (+)-phorboxazole A endeavor, we recognized and exploited the inherent pseudo symmetry of the 2,6- cis

  17. Modulation of the partition coefficient between octanol and buffer at pH 7.4 and pKa to achieve the optimum balance of blood clearance and volume of distribution for a series of tetrahydropyran histamine type 3 receptor antagonists. (United States)

    Hay, Tanya; Jones, Rhys; Beaumont, Kevin; Kemp, Mark


    The relationship between rat pharmacokinetics and physicochemical parameters [the partition coefficient between octanol and buffer at pH 7.4 (log D((7.4))) and pK(a)] was studied for a series of tetrahydropyran compounds. Sixteen compounds ranging in log D((7.4)) 0.1 to 1.8 were administered intravenously to rats, and the pharmacokinetic parameters were determined from blood concentration time curves. Across the series, a weak correlation was observed between log D((7.4)) and blood clearance, suggesting that log D((7.4)) values less than 0.5 were required to prevent clearance at hepatic blood flow. In terms of the volume of distribution (V(d)), the compounds fell into three distinct subseries characterized by the number of basic centers and differences in ionization of each basic center at physiological pH. These were referred to as the monobasic, weak second base, and strong second base subseries. All the compounds exhibited V(d) greater than body water, as would be expected from their lipophilic and basic nature. For a given clog P, the strong second base subseries showed higher V(d) than the weak second base subseries, which in turn exhibited higher values than the monobasic subseries. In addition, for the weak second base subseries, V(d) could be tuned by modulating the pK(a) of the second basic center. This relationship was rationalized in respect to the interactions of the ionizable centers with phospholipid heads in the cell membrane and/or lysosomal trapping. Compounds in the weak second base subseries showed optimal V(d), and when combined with a log D((7.4)) of 0.1, driving to moderate blood clearance, one compound showed the optimal pharmacokinetic profile.

  18. Ring-Opening Reactions of Aziridines Fused to a Conformationally Locked Tetrahydropyran Ring

    Czech Academy of Sciences Publication Activity Database

    Karban, Jindřich; Kroutil, J.; Buděšínský, Miloš; Sýkora, Jan; Císařová, I.


    Roč. 2009, č. 36 (2009), s. 6399-6406 ISSN 1434-193X R&D Projects: GA AV ČR IAA400720703; GA AV ČR IAA400720706 Institutional research plan: CEZ:AV0Z40720504; CEZ:AV0Z40550506 Keywords : aziridines * carbohydrates * regioselectivity Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.096, year: 2009

  19. Synthesis, characterization and biological activity of ring-substituted 6-benzylamino-9-tetrahydropyran-2-yl and 9-tetrahydrofuran-2-ylpurine derivatives

    Czech Academy of Sciences Publication Activity Database

    Szüčová, Lucie; Spíchal, Lukáš; Doležal, Karel; Zatloukal, Marek; Greplová, Jarmila; Galuszka, P.; Kryštof, Vladimír; Voller, Jiří; Popa, Igor; Massino, F.J.; Jorgensen, J.E.; Strnad, Miroslav


    Roč. 17, č. 5 (2009), s. 1938-1947 ISSN 0968-0896 R&D Projects: GA MŠk 1M06030; GA ČR GA522/09/1576; GA ČR(CZ) GA522/08/0920 Institutional research plan: CEZ:AV0Z50380511 Keywords : Cytokinins * Antisenescence * Receptor Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.822, year: 2009

  20. Configuration-dependent conformational transmission in trigonal-bipyramidal phosphorus(V) compounds. Enhanced gauche (-) population around the C(5)-C(6) linkage in 6-phosphorus(V) phosphorylated tetramethyl-a-D-galactopyranoside

    NARCIS (Netherlands)

    Vries, de N.K.; Buck, H.M.


    A 300-MHz 1H NMR variable-temperature study of the 1'-phosphorylated trigonal-bipyramidal (TBP) tetrahydropyran-2-methyl model compound 4 is reported. For this compound, in which both the equatorial and axial sites undergoing phosphorus pseudorotation bear a tetrahydro-pyran-2-methyl group, a

  1. Hydroxyl-substituted ladder polyethers via selective tandem epoxidation/cyclization sequence. (United States)

    Czabaniuk, Lara C; Jamison, Timothy F


    A new and highly selective method for the synthesis of hydroxyl-substituted tetrahydropyrans is described. This method utilizes titanium(IV) isopropoxide and diethyl tartrate to perform a diastereoselective epoxidation followed by in situ epoxide activation and highly selective endo-cyclization to form the desired tetrahydropyran ring. The HIJ ring fragment of the marine ladder polyether yessotoxin was synthesized using this two-stage tactic that proceeds with high efficiency and excellent regioselectivity.

  2. Trans-Selective Rhodium Catalysed Conjugate Addition of Organoboron Reagents to Dihydropyranones

    Directory of Open Access Journals (Sweden)

    Hannah J. Edwards


    Full Text Available The selective synthesis of 2,6-trans-tetrahydropyran derivatives employing the rhodium catalysed addition of organoboron reagents to dihydropyranone templates, derived from a zinc-catalysed hetero-Diels-Alder reaction, is reported. The addition of both arylboronic acids and potassium alkenyltrifluoroborates have been accomplished in high yields using commercially-available [Rh(cod(OH]2 catalyst. The selective formation of the 2,6-trans-tetrahydropyran stereoisomer is consistent with a mechanism involving alkene association and carbometalation on the less hindered face of the dihydropyranone.

  3. 10a-Hydroxy-9-(4-methoxyphenyl-3,4,5,6,7,8a,9,10a-octahydro-1H-xanthene-1,8(2H-dione

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun


    Full Text Available In the title compound, C20H22O5, the tetrahydropyran, cyclohexene and cyclohexane rings of the xanthene ring system adopt half-chair, half-boat and chair conformations, respectively. The mean plane of the four roughly planar atoms of the tetrahydropyran ring (r.m.s. deviation = 0.111 Å forms a dihedral angle of 82.91 (4° with the methoxybenzene group. In the crystal, molecules are linked via O—H...O and C—H...O hydrogen bonds into sheets lying parallel to the ac plane. The crystal is further consolidated by weak C—H...π interactions.

  4. Journal of Chemical Sciences | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences. Ruli Borah. Articles written in Journal of Chemical Sciences. Volume 123 Issue 5 September 2011 pp 623-630. Investigation of Prins reaction for the synthesis of 2, 4- disubstituted tetrahydropyran derivatives and 1, 3-dioxanes using polyaniline supported acid as reusable ...

  5. Phase equilibrium measurements of structure II clathrate hydrates of hydrogen with various promoters

    NARCIS (Netherlands)

    Torres Trueba, A.; Rovetto, L.J.; Florusse, L.J.; Kroon, M.C.; Peters, C.J.


    Phase equilibrium measurements of single and mixed organic clathrate hydrates with hydrogen were determined within a pressure range of 2.0–14.0 MPa. The organic compounds studied were furan, 2,5-dihydrofuran, tetrahydropyran, 1,3-dioxolane and cyclopentane. These organic compounds are known to form

  6. A nuclear magnetic resonance study of conformational transmission in phosphorylated pyranosides

    International Nuclear Information System (INIS)

    Vries, N.K. de.


    This thesis describes an experimental NMR study, combined with MNDO calculations, on the conformational preferences of the exocyclic bond of 6-phosphorylated pyranosides and tetrahydropyran-2-methyl compounds. The various factors influencing the rotamer population distribution around this O-C-C-O fragment, e.g. solvent polarity, stereoelectronic effects and coordination of phosphorus, are analysed. 150 refs.; 25 figs.; 16 tabs

  7. 1,4-Hydroiodination of dienyl alcohols with TMSI to form homoallylic alcohols containing a multisubstituted Z-alkene and application to Prins cyclization. (United States)

    Xu, Yongjin; Yin, Zhiping; Lin, Xinglong; Gan, Zubao; He, Yanyang; Gao, Lu; Song, Zhenlei


    A regioselective 1,4-hydroiodination of dienyl alcohols has been developed using trimethylsilyl iodide as Lewis acid and iodide source. A range of homoallylic alcohols containing a multisubstituted Z-alkene was synthesized with good to excellent configurational control. The approach was applied in sequential hydroiodination/Prins cyclization to afford multisubstituted tetrahydropyrans diastereoselectively.

  8. Synthesis of Ophiocerins from Non-Carbohydrate Sources

    International Nuclear Information System (INIS)

    Hong, Hui Jeong; Lee, Dong Min; Kang, Han Young


    Direct and unified synthetic routes to ophiocerin A, B, C, and D have been successfully developed. These syntheses are based on ring-closing metathesis and non-carbohydrate starting materials and are simpler and more efficient than the previous syntheses, as demonstrated in the case of ophiocerin B (2) (eleven steps from methyl α-D-glucopyranoside vs. four steps from 4-penten-2-ol) and ophiocerin A (1) (twelve steps from methyl α-D-glucopyranoside vs. three steps from 4-penten-2-ol). These routes will be useful for the practical synthesis of related natural products. Ophiocerins are comprised of four compounds isolated from the aqueous fungi Ophioceras venezuelense, each bearing a tetrahydropyran ring with an interesting array of substituents (Figure 1). Since substituted tetrahydropyran rings are found in many biologically important natural products, ophiocerins have attracted the attention of synthetic chemists

  9. Synthesis of analogues of Eunicea gamma-cembranolides containing cyclic ethers via saponification. (United States)

    Rodríguez, A D; Piña, I C; Acosta, A L; Ramírez, C; Soto, J J


    A method for the synthesis of derivatives of the lead structures euniolide (1), 12,13-bisepieupalmerin (2), and eupalmerin acetate (3) containing tetrahydrofuran and tetrahydropyran ring systems was developed on the basis of alkali-induced intramolecular oxacyclizations. Representatives of the new analogues were submitted to the in vitro antitumor cell-line-screening program of the National Cancer Institute (NCI). While it was shown that a variety of structural modifications are possible, these transformations led typically to nontoxic synthetic cembranoids.

  10. Effects of α-amino acids and small peptides on the rate of an SN1 acetal hydrolysis reaction in aqueous solution : The interplay of hydrophobic and hydrophilic solute hydration

    NARCIS (Netherlands)

    Streefland, L.; Blandamer, M.J; Engberts, J.B.F.N.

    The effects of small amounts of anionic a-amino acids and several small peptides on the kinetics of the S(N)1 hydrolysis of 2-(4-nitrophenoxy)tetrahydropyran have been investigated at pH 11 and 40 degrees C. The rate-retarding effect at 1 molal of cosolute is plotted as ln (k(m=1)/k(m=0)) versus the

  11. Green chemistry: solvent- and metal-free Prins cyclization. Application to sequential reactions. (United States)

    Clarisse, Damien; Pelotier, Béatrice; Piva, Olivier; Fache, Fabienne


    Prins cyclization between a homoallylic alcohol and an aldehyde, promoted by trimethylsilyl halide, afforded 4-halo-tetrahydropyrans with good to excellent yields. Thanks to the absence of the solvent and metal, the THP thus obtained have been implicated without purification in several other reactions, in a sequential way, affording in particular new indole derivatives. This journal is © The Royal Society of Chemistry 2012

  12. Process for the reduction of nitrogen oxides in an effluent

    Energy Technology Data Exchange (ETDEWEB)

    Epperly, W.R.; Sullivan, J.C.; Sprague, B.N.


    This patent describes a process for the reduction of the concentration of nitrogen oxides in the effluent from the combustion of a carbonaceous fuel. The process comprises introducing a treatment agent which comprises a composition selected from the group consisting of NH/sub 4/-lignosulfonate, calcium lignosulfonate, 2-furoic acid, 1,3 dioxolane, tetrahydrofuran, furfurylamine, furfurylalcohol, gluconic acid, citric acid, n-butyl acetate, 1,3 butylene glycol, methylal, tetrahydrofuryl alcohol, furan, fish oil, coumalic acid, furfuryl acetate, tetrahydrofuran 2,3,4,5-tetracarboxylic acid, tetrahydrofurylamine, furylacrylic acid, tetrahydropyran, 2,5-furandimethanol, mannitol, hexamethylenediamine, barbituric acid, acetic anhydride, oxalic acid, mucic acid and d-galactose.

  13. Direct Enantioselective Reaction between Hemiacetals and Phosphorus Ylides: Important Role of a By-Product in the Asymmetric Transformation. (United States)

    Wang, Rui; Wang, Linqing; Yang, Dongxu; Li, Dan; Liu, Xihong; Wang, Pengxin; Wang, Kezhou; Zhu, Haiyong; Bai, Lutao


    By employing a simple in-situ generated magnesium catalyst, the direct asymmetric reaction between hemiacetals and P-ylides is achieved via a tandem Wittig-oxa-Michael reaction sequence. Enantioenriched chromans, isochromans and tetrahydropyrans can be obtained in good chemical yields. (-)-Erythrococcamide B can be asymmetrically synthesized through this synthetic technique. In this work, the by-product, TPO, was identified as a necessary additive in this asymmetric synthetic method. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Potent, selective, orally bioavailable inhibitors of tumor necrosis factor-alpha converting enzyme (TACE): discovery of indole, benzofuran, imidazopyridine and pyrazolopyridine P1' substituents. (United States)

    Lu, Zhonghui; Ott, Gregory R; Anand, Rajan; Liu, Rui-Qin; Covington, Maryanne B; Vaddi, Krishna; Qian, Mingxin; Newton, Robert C; Christ, David D; Trzaskos, James; Duan, James J-W


    Potent and selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) were discovered with several new heterocyclic P1' groups in conjunction with cyclic beta-amino hydroxamic acid scaffolds. Among them, the pyrazolopyridine provided the best overall profile when combined with tetrahydropyran beta-amino hydroxamic acid scaffold. Specifically, inhibitor 49 showed IC(50) value of 1 nM against porcine TACE and 170 nM in the suppression of LPS-induced TNF-alpha of human whole blood. Compound 49 also displayed excellent selectivity over a wide panel of MMPs as well as excellent oral bioavailability (F%>90%) in rat n-in-1 PK studies.

  15. Epoxide hydrolase-lasalocid a structure provides mechanistic insight into polyether natural product biosynthesis. (United States)

    Wong, Fong T; Hotta, Kinya; Chen, Xi; Fang, Minyi; Watanabe, Kenji; Kim, Chu-Young


    Biosynthesis of some polyether natural products involves a kinetically disfavored epoxide-opening cyclic ether formation, a reaction termed anti-Baldwin cyclization. One such example is the biosynthesis of lasalocid A, an ionophore antibiotic polyether. During lasalocid A biosynthesis, an epoxide hydrolase, Lsd19, converts the bisepoxy polyketide intermediate into the tetrahydrofuranyl-tetrahydropyran product. We report the crystal structure of Lsd19 in complex with lasalocid A. The structure unambiguously shows that the C-terminal domain of Lsd19 catalyzes the intriguing anti-Baldwin cyclization. We propose a general mechanism for epoxide selection by ionophore polyether epoxide hydrolases.

  16. Studies toward brevisulcenal F via convergent strategies for marine ladder polyether synthesis. (United States)

    Katcher, Matthew; Jamison, Timothy F


    Shortly after the initial isolation of marine ladder polyether natural products, biomimetic epoxide-opening cascade reactions were proposed as an efficient strategy for the synthesis of these compounds. However, difficulties in assembling the cascade precursors have limited the realization of these cascades. In this report, we describe strategies that provide convergent access to cascade precursors via regioselective allylation and efficient fragment coupling. We then investigate epoxide-opening cascades promoted by strong bases for the formation of fused tetrahydropyrans. These strategies are evaluated in the context of the synthesis of rings CDEFG of brevisulcenal F.

  17. Neutral complexes of the indium dihalides

    Energy Technology Data Exchange (ETDEWEB)

    Sinclair, I.; Worrall, I.J. (Lancaster Univ. (UK))


    The neutral complexes In/sub 2/X/sub 4/.2L (X=Cl, Br, I; L 1,4-dioxan, tetrahydropyran, tetrahydrofuran, tetrahydrothiophene), In/sub 2/X/sub 4/.2L (X=Br, I; Ldimethylsulphide), In/sub 2/X/sub 4/.4L (X=Cl, Br, I; Lpiperidine, piperazine, morpholine), and In/sub 2/X/sub 4/.4L (X=Br, I; L=pyridine, dimethylsulphoxide) have been prepared. Solid state Raman spectra indicate that the compounds contain indium-indium bonds.

  18. 4,5,7,8,17-Pentahydroxy-14,18-dimethyl-6-methylene-3,10-dioxapentacyclo[,7.04,19.013,18]nonadec-14-ene-9,16-dione methanol solvate dihydrate

    Directory of Open Access Journals (Sweden)

    Chin Hoe Teh


    Full Text Available The title quassinoid compound, C20H24O9·CH3OH·2H2O, is a natural eurycomanone isolated from the roots of Eurycoma longifolia. The molecules contain a fused five-ring system, with one tetrahydrofuran ring adopting an envelope conformation, one tetrahydropyran-2-one ring in a screw boat conformation, one cyclohexenone ring in a half-chair conformation and two cyclohexane rings in chair conformations. Intramolecular C—H...O interactions generate S(5 ring motifs and an O—H...O interaction generates an S(7 ring motif. In the crystal, molecules are linked via intermolecular O—H...O interactions along the b axis and further stacked along a axis. The absolute configuration of the title compound was inferred from previously solved structures of its analogues.

  19. Radical fragmentation of six-membered oxygen-containing heterocycles

    International Nuclear Information System (INIS)

    Petryaev, E.P.; Kosobutskij, V.S.; Shadyro, O.I.


    Using chromatography, the composition and radiation-chemical yields of final products of desctruction of six-member saturated oxygen-containing heterocycles (the effect of #betta#-radiation on aqueous solutions of tetrahydropyran, 1,3-dioxane, 2,2 dimethyl-1,3 dioxane, 1,4-dioxane, paraldehyde) have been determined. It is established that the identified products are formed at the expense of decomposition of primary radicals of the initial compounds and point to the realization of the following fragmentation ways: 1) #betta#-scattering, 2) #betta#-scattering with a subsequent 1,5 migration of an H atom, 3) simultaneous rupture of two vicinal, relative to the radical center, bonds. A formation mechanism of the substances desctruction products is suggested. Material balance of the product yields of 1,3-dioxane radical synchronous decomposition is presented

  20. Synthesis of the ABCDEFG ring system of maitotoxin. (United States)

    Nicolaou, K C; Aversa, Robert J; Jin, Jian; Rivas, Fatima


    Maitotoxin (1) continues to fascinate scientists not only because of its size and potent neurotoxicity but also due to its molecular architecture. To provide further support for its structure and facilitate fragment-based biological studies, we developed an efficient chemical synthesis of the ABCDEFG segment 3 of maitotoxin. (13)C NMR chemical shift comparisons of synthetic 3 with the corresponding values for the same carbons of maitotoxin revealed a close match, providing compelling evidence for the correctness of the originally assigned structure to this polycyclic system of the natural product. The synthetic strategy for the synthesis of 3 relied heavily on our previously developed furan-based technology involving sequential Noyori asymmetric reduction and Achmatowicz rearrangement for the construction of the required tetrahydropyran building blocks, and employed a B-alkyl Suzuki coupling and a Horner-Wadsworth-Emmons olefination to accomplish their assembly and elaboration to the final target molecule.

  1. Assembly of Four Diverse Heterocyclic Libraries Enabled by Prins Cyclization, Au-Catalyzed Enyne Cycloisomerization, and Automated Amide Synthesis (United States)

    Cui, Jiayue; Chai, David I.; Miller, Christopher; Hao, Jason; Thomas, Christopher; Wang, JingQi; Scheidt, Karl A.; Kozmin, Sergey A.


    We describe a unified synthetic strategy for efficient assembly of four new heterocyclic libraries. The synthesis began by creating a range of structurally diverse pyrrolidinones or piperidinones. Such compounds were obtained in a simple one-flask operation starting with readily available amines, ketoesters, and unsaturated anhydrides. The use of tetrahydropyran-containing ketoesters, which were rapidly assembled by our Prins cyclization protocol, enabled efficient fusion of pyran and piperidinone cores. A newly developed Au(I)-catalyzed cycloisomerization of alkyne-containing enamides further expanded heterocyclic diversity by providing rapid entry into a wide range of bicyclic and tricyclic dienamides. The final stage of the process entailed diversification of each of the initially produced carboxylic acids using a fully automated platform for amide synthesis, which delivered 1872 compounds in high diastereomeric and chemical purity. PMID:22860634

  2. Total synthesis of mycalamide A. (United States)

    Sohn, Jeong-Hun; Waizumi, Nobuaki; Zhong, H Marlon; Rawal, Viresh H


    This communication describes a concise and efficient total synthesis of mycalamide A by the convergent coupling of pederic acid unit with the mycalamine unit. The left-half, (+)-7-benzoylpederic acid, was synthesized from (2R,3R)-3-methylpent-4-en-2-ol in seven steps and 34.6% overall yield through a route that features a one-step Pd(II)-catalyzed tandem Wacker/Heck cyclization reaction to prepare the tetrahydropyran ring system. The right-half, the mycalamine unit, was synthesized in 21 steps and 10.5% overall yield from diethyl d-tartrate. Effective, stereoselective methods were developed for the assembly of the two parts to yield either mycalamide A or C(10)-epi-mycalamide A.

  3. Synthetic and mechanistic aspects of titanium-mediated carbonyl olefinations

    Energy Technology Data Exchange (ETDEWEB)

    Petasis, N.A.; Staszewski, J.P.; Hu, Yong-Han; Lu, Shao-Po [Univ. of Southern California, Los Angeles, CA (United States)


    A new method for the olefination of carbonyl compounds with dimethyl titanocene, and other related bishydrocarbyl titanocene derivatives has been recently developed in the author`s laboratories. This process is experimentally convenient and works with various types of carbonyl compounds, including aldehydes, ketones, esters, lactones, carbonates, anhydrides, amides, imides, lactams, thioesters, selenoesters, and acylsilanes. More recent studies have focused on the scope and utility of this reaction, including mechanistic studies and synthetic applications. In addition to varying the reaction conditions, the authors have examined several mixed titanocene derivatives and have found ways for carrying out this type of olefination at room temperature, such as the use of tris(trimethylsilyl) titanacyclobutene. The authors have also employed this reaction in the modification of carbohydrates and cyclobutenediones. This olefination was also followed-up with subsequent transformations to produce carbocycles and heterocycles, including tetrahydrofurans and tetrahydropyrans.

  4. Studies toward the unique pederin family member psymberin: full structure elucidation, two alternative total syntheses, and analogs. (United States)

    Feng, Yu; Jiang, Xin; De Brabander, Jef K


    Two synthetic approaches to psymberin have been accomplished. A highly convergent first generation synthesis led to the complete stereochemical assignment and demonstrated that psymberin and irciniastatin A are identical compounds. This synthesis featured a diastereoselective aldol coupling between the aryl fragment and a central tetrahydropyran core and a novel one-pot procedure to convert an amide, via intermediacy of a sensitive methyl imidate, to the N-acyl aminal reminiscent of psymberin. The highlights of the second generation synthesis include an efficient iridium-catalyzed enantioselective bisallylation of neopentyl glycol and a stepwise Sonogashira coupling/cycloisomerization/reduction sequence to construct the dihydroisocoumarin unit. The two synthetic avenues were achieved in 17-18 steps (longest linear sequence, ~14-15 isolations) from 3 fragments prepared in 7-8 (first generation) and 3-8 (second generation) steps each. This convergent approach allowed for the preparation of sufficient amounts of psymberin (~ 0.5 g) for follow-up biological studies. Meanwhile, our highly flexible strategy enabled the design and synthesis of multiple analogs, including a psymberin-pederin hybrid, termed psympederin, that proved crucial to a comprehensive understanding of the chemical biology of psymberin and related compounds that will be described in a subsequent manuscript.

  5. Alkene Metathesis Catalysis: A Key for Transformations of Unsaturated Plant Oils and Renewable Derivatives

    Directory of Open Access Journals (Sweden)

    Dixneuf Pierre H.


    Full Text Available This account presents the importance of ruthenium-catalysed alkene cross-metathesis for the catalytic transformations of biomass derivatives into useful intermediates, especially those developed by the authors in the Rennes (France catalysis team in cooperation with chemical industry. The cross-metathesis of a variety of functional alkenes arising from plant oils, with acrylonitrile and fumaronitrile and followed by catalytic tandem hydrogenation, will be shown to afford linear amino acid derivatives, the precursors of polyamides. The exploration of cross-metathesis of bio-sourced unsaturated nitriles with acrylate with further catalytic hydrogenation has led to offer an excellent route to α,ω-amino acid derivatives. That of fatty aldehydes has led to bifunctional long chain aldehydes and saturated diols. Two ways of access to functional dienes by ruthenium-catalyzed ene-yne cross-metathesis of plant oil alkene derivatives with alkynes and by cross-metathesis of bio-sourced alkenes with allylic chloride followed by catalytic dehydrohalogenation, are reported. Ricinoleate derivatives offer a direct access to chiral dihydropyrans and tetrahydropyrans via ring closing metathesis. Cross-metathesis giving value to terpenes and eugenol for the straightforward synthesis of artificial terpenes and functional eugenol derivatives without C=C bond isomerization are described.

  6. Antitermite Activities of C. decidua Extracts and Pure Compounds against Indian White Termite Odontotermes obesus (Isoptera: Odontotermitidae

    Directory of Open Access Journals (Sweden)

    Ravi Kant Upadhyay


    Full Text Available In the present investigation, we have tested antitermite responses of Capparis decidua stem, root, flower, and fruit extracts and pure compounds to Odontotermes obesus in various bioassays. Crude stem extract has shown very high susceptibility and very low LD50 values, that is, 14.171 μg/mg in worker termites. From stem extract, three pure compounds were isolated in pure form namely, heneicosylhexadecanoate (CDS2, triacontanol (CDS3, and 2-carboxy-1, 1-dimethylpyrrolidine (CDS8 which have shown very low LD50 value in a range of 5.537–10.083 μg/mg. Similarly, one novel compound 6-(1-hydroxy-non-3-enyl-tetrahydropyran-2-one (CDF1 was isolated from flower extract that has shown an LD50 8.08 μg/gm. Repellent action of compounds was tested in a Y-shaped glass olfactometer in which CDF1 compounds have significantly repelled termites to the opposite arm. Besides this, C. decidua extracts have shown significant reduction (P<0.05 and 0.01 in termite infestation in garden saplings when it was coated on cotton tags and employed over tree trunks. Further, C. deciduas stem extract was used for wood seasoning, which gave very good results as test wood sticks have shown significantly (P<0.05 and 0.01 very low termite infestation.

  7. Synthesis and biological investigation of PIM mimics carrying biotin or a fluorescent label for cellular imaging. (United States)

    Front, Sophie; Bourigault, Marie-Laure; Rose, Stéphanie; Noria, Ségueni; Quesniaux, Valérie F J; Martin, Olivier R


    Phosphatidyl inositol mannosides (PIMs) are constituents of the mycobacterial cell wall; these glycolipids are known to exhibit potent inhibitory activity toward the LPS-induced production of cytokines by macrophages, and therefore have potential as anti-inflammatory agents. Recently, heterocyclic analogues of PIMs in which the inositol is replaced by a piperidine (aza-PIM mimics) or a tetrahydropyran moiety (oxa-PIM mimics) have been prepared by short synthetic sequences and shown to retain the biological activity of the parent PIM structures. In this investigation, the aza-PIM analogue was used as a convenient scaffold to link biotin or a fluorescent label (tetramethyl-rhodamine) by way of an aminocaproyl spacer, with the goal of using these conjugates for intracellular localization and for the study of the mechanism of their antiinflammatory action. The synthesis of these compounds is reported, as well as the evaluation of their activities as inhibitors of LPS-induced cytokine production by macrophages (TNFα, IL12p40); preliminary investigations by FACS and confocal microscopy indicated that PIM-biotin conjugate binds to macrophage membranes with rapid kinetics.

  8. Exploration of flexible phenylpropylurea scaffold as novel cardiac myosin activators for the treatment of systolic heart failure. (United States)

    Manickam, Manoj; Jalani, Hitesh B; Pillaiyar, Thanigaimalai; Sharma, Niti; Boggu, Pulla Reddy; Venkateswararao, Eeda; Lee, You-Jung; Jeon, Eun-Seok; Jung, Sang-Hun


    A series of flexible urea derivatives have been synthesized and demonstrated as selective cardiac myosin ATPase activator. Among them 1-phenethyl-3-(3-phenylpropyl)urea (1, cardiac myosin ATPase activation at 10 μM = 51.1%; FS = 18.90; EF = 12.15) and 1-benzyl-3-(3-phenylpropyl)urea (9, cardiac myosin ATPase activation = 53.3%; FS = 30.04; EF = 18.27) showed significant activity in vitro and in vivo. The change of phenyl ring with tetrahydropyran-4-yl moiety viz., 1-(3-phenylpropyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)urea (14, cardiac myosin ATPase activation = 81.4%; FS = 20.50; EF = 13.10), and morpholine moiety viz., 1-(2-morpholinoethyl)-3-(3-phenylpropyl)urea (21, cardiac myosin ATPase activation = 44.0%; FS = 24.79; EF = 15.65), proved to be efficient to activate the cardiac myosin. The potent compounds 1, 9, 14 and 21 were found to be selective for cardiac myosin over skeletal and smooth myosins. Thus, these urea derivatives are potent scaffold to develop as a newer cardiac myosin activator for the treatment of systolic heart failure. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Crystal structure of diaphorin methanol monosolvate isolated from Diaphorina citri Kuwayama, the insect vector of citrus greening disease. (United States)

    Szebenyi, D Marian; Kriksunov, Irina; Howe, Kevin J; Ramsey, John S; Hall, David G; Heck, Michelle L; Krasnoff, Stuart B


    The title compound C 22 H 39 NO 9 ·CH 3 OH [systematic name: ( S )- N -(( S )-{(2 S ,4 R ,6 R )-6-[( S )-2,3-di-hydroxy-prop-yl]-4-hy-droxy-5,5-di-methyl-tetra-hydro-2 H -pyran-2-yl}(hy-droxy)meth-yl)-2-hy-droxy-2-[(2 R ,5 R ,6 R )-2-meth-oxy-5,6-dimeth-yl-4-methyl-ene-tetra-hydro-2 H -pyran-2-yl]acetamide methanol monosolvate], was isolated from the Asian citrus psyllid, Diaphorina citri Kuwayama, and crystallizes in the space group P 2 1 . ' Candidatus Profftella armatura' a bacterial endosymbiont of D. citri , biosynthesizes diaphorin, which is a hybrid polyketide-nonribosomal peptide comprising two highly substituted tetra-hydro-pyran rings joined by an N -acyl aminal bridge [Nakabachi et al. (2013 ▸). Curr. Biol. 23 , 1478-1484]. The crystal structure of the title compound establishes the complete relative configuration of diaphorin, which agrees at all nine chiral centers with the structure of the methanol monosolvate of the di- p -bromo-benzoate derivative of pederin, a biogenically related compound whose crystal structure was reported previously [Furusaki et al. (1968 ▸). Tetra-hedron Lett. 9 , 6301-6304]. Thus, the absolute configuration of diaphorin is proposed by analogy to that of pederin.

  10. Crystal structure of diaphorin methanol monosolvate isolated from Diaphorina citri Kuwayama, the insect vector of citrus greening disease

    Directory of Open Access Journals (Sweden)

    D. Marian Szebenyi


    Full Text Available The title compound C22H39NO9·CH3OH [systematic name: (S-N-((S-{(2S,4R,6R-6-[(S-2,3-dihydroxypropyl]-4-hydroxy-5,5-dimethyltetrahydro-2H-pyran-2-yl}(hydroxymethyl-2-hydroxy-2-[(2R,5R,6R-2-methoxy-5,6-dimethyl-4-methylenetetrahydro-2H-pyran-2-yl]acetamide methanol monosolvate], was isolated from the Asian citrus psyllid, Diaphorina citri Kuwayama, and crystallizes in the space group P21. `Candidatus Profftella armatura' a bacterial endosymbiont of D. citri, biosynthesizes diaphorin, which is a hybrid polyketide–nonribosomal peptide comprising two highly substituted tetrahydropyran rings joined by an N-acyl aminal bridge [Nakabachi et al. (2013. Curr. Biol. 23, 1478–1484]. The crystal structure of the title compound establishes the complete relative configuration of diaphorin, which agrees at all nine chiral centers with the structure of the methanol monosolvate of the di-p-bromobenzoate derivative of pederin, a biogenically related compound whose crystal structure was reported previously [Furusaki et al. (1968. Tetrahedron Lett. 9, 6301–6304]. Thus, the absolute configuration of diaphorin is proposed by analogy to that of pederin.

  11. Electrochemical behavior of lithium imide/cyclic ether electrolytes for 4 V lithium metal rechargeable batteries

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.; Yasukawa, Eiki; Mori, Shoichiro


    To develop organic electrolytes for 4 V lithium metal rechargeable batteries, LiN(SO{sub 2}CF{sub 3}){sub 2} electrolytes with five-, six-, and seven-membered cyclic ether solvents were characterized. Among these examined electrolytes, LiN(SO{sub 2}CF{sub 3}){sub 2}/tetrahydropyran (THP) electrolyte was found to possess the most advantages, such as high cycling efficiency, good oxidation stability, and high boiling point. Furthermore, lithium cycling efficiency and conductivity were improved by mixing 50% ethylene carbonate (EC) in 1 mol/dm{sup 3} LiN(SO{sub 2}CF{sub 3}){sub 2}/THP electrolyte. By using LiN(SO{sub 2}C{sub 2}F{sub 5}){sub 2} solute as an alternative to LiN(SO{sub 2}CF{sub 3}){sub 2} in EC + THP (1:1) electrolyte, corrosion of the aluminum current collector was inhibited and therefore, excellent cycling performance of a Li/LiMn{sub 2}O{sub 4} coin cell was realized. It was also found that lithium cycling efficiency increased with decreasing deposition current density or increasing dissolution current density. Especially at deposition/dissolution current densities of 0.2/0.6 mA/cm{sup 2}, the observed lithium cycling efficiency in 1 mol/dm{sup 3} LiN(SO{sub 2}C{sub 2}F{sub 5}){sub 2}/EC + THP (1:1) electrolyte was above 99%. Thermal tests further disclosed that this mixed electrolyte has good thermal stability even in the presence of lithium metal or cathode materials.

  12. Curcumin Derivative Epigenetically Reactivates Nrf2 Antioxidative Stress Signaling in Mouse Prostate Cancer TRAMP C1 Cells. (United States)

    Li, Wenji; Su, Zheng-Yuan; Guo, Yue; Zhang, Chengyue; Wu, Renyi; Gao, Linbo; Zheng, Xi; Du, Zhi-Yun; Zhang, Kun; Kong, Ah-Ng


    The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-bis-(3,4,5-trimethoxybenzylidene)-tetrahydro-thiopyran-4-one (F10) and (3E,5E)-3,5-bis-(3,4,5-trimethoxy-benzylidene)-tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin, and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways. We performed real-time quantitative PCR and Western blotting to investigate the effects of F10 and E10 on Nrf2, correlated phase II detoxification genes. We also measured expression and activity of DNMTand HDAC enzymes. Enrichment of H3K27me3 on the promoter region of Nrf2 was explored with a chromatin immunoprecipitation (ChIP) assay. Methylation of the CpG region in Nrf2 promoter was doubly examined by bisulfite genomic sequencing (BGS) and methylation DNA immunoprecipitation (MeDIP). Compared with curcumin and SFN, F10 is more potent in activating Nrf2-ARE pathways. Both F10 and E10 enhanced level of Nrf2 and the correlated phase II detoxifying genes. BGS and MeDIP assays indicated that F10 but not E10 hypomethylated the Nrf2 promoter. F10 also downregulated the protein level of DNMT1, DNMT3a, DNMT3b, HDAC1, HDAC4, and HDAC7 and the activity of DNMTs and HDACs. F10 but not E10 effectively reduced the accumulation of H3k27me3 on the promoter of Nrf2. F10 and E10 can activate the Nrf2-ARE pathway and increase the level of Nrf2 and correlated phase II detoxification genes. The reactivation effect on Nrf2 by F10 in TRAMP C1 may come from demethylation, decrease of HDACs, and inhibition of H3k27me3 accumulation.

  13. O-heterocyclic derivatives with antibacterial properties from marine bacterium Bacillus subtilis associated with seaweed, Sargassum myriocystum. (United States)

    Chakraborty, Kajal; Thilakan, Bini; Chakraborty, Rekha Devi; Raola, Vamshi Krishna; Joy, Minju


    The brown seaweed, Sargassum myriocystum associated with heterotrophic bacterium, Bacillus subtilis MTCC 10407 (JF834075) exhibited broad-spectra of potent antibacterial activities against pathogenic bacteria Aeromonas hydrophila, Vibrio vulnificus, and Vibrio parahaemolyticus. B. subtilis MTCC 10407 was found to be positive for polyketide synthetase (pks) gene, and therefore, was considered to characterize secondary metabolites bearing polyketide backbone. Using bioassay-guided fractionation, two new antibacterial O-heterocyclic compounds belonging to pyranyl benzoate analogs of polyketide origin, with activity against pathogenic bacteria, have been isolated from the ethyl acetate extract of B. subtilis MTCC 10407. In the present study, the secondary metabolites of B. subtilis MTCC 10407 with potent antibacterial action against bacterial pathogens was recognized to represent the platform of pks-1 gene-encoded products. Two homologous compounds 3 (3-(methoxycarbonyl)-4-(5-(2-ethylbutyl)-5,6-dihydro-3-methyl-2H-pyran-2-yl)-butyl benzoate) and 4 [2-(8-butyl-3-ethyl-3,4,4a,5,6,8a-hexahydro-2H-chromen-6-yl)-ethyl benzoate] also have been isolated from the ethyl acetate extract of host seaweed S. myriocystum. The two compounds isolated from ethyl acetate extract of S. myriocystum with lesser antibacterial properties shared similar structures with the compounds purified from B. subtilis that suggested the ecological and metabolic relationship between these compounds in seaweed-bacterial relationship. Tetrahydropyran-2-one moiety of the tetrahydropyrano-[3,2b]-pyran-2(3H)-one system of 1 might be cleaved by the metabolic pool of seaweeds to afford methyl 3-(dihydro-3-methyl-2H-pyranyl)-propanoate moiety of 3, which was found to have no significant antibacterial activity. It is therefore imperative that the presence of dihydro-methyl-2H-pyran-2-yl propanoate system is essentially required to impart the greater activity. The direct involvement of polarisability (Pl) with

  14. Geometrically and conformationally restrained cinnamoyl compounds as inhibitors of HIV-1 integrase: synthesis, biological evaluation, and molecular modeling. (United States)

    Artico, M; Di Santo, R; Costi, R; Novellino, E; Greco, G; Massa, S; Tramontano, E; Marongiu, M E; De Montis, A; La Colla, P


    Various cinnammoyl-based structures were synthesized and tested in enzyme assays as inhibitors of the HIV-1 integrase (IN). The majority of compounds were designed as geometrically or conformationally constrained analogues of caffeic acid phenethyl ester (CAPE) and were characterized by a syn disposition of the carbonyl group with respect to the vinylic double bond. Since the cinnamoyl moiety present in flavones such as quercetin (inactive on HIV-1-infected cells) is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and conformational properties of the designed compounds were taken into account through analysis of X-ray structures available from the Cambridge Structural Database. The polyhydroxylated analogues were prepared by reacting 3,4-bis(tetrahydropyran-2-yloxy)benzaldehyde with various compounds having active methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3-diacetylbenzene, 2, 4-dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro-1, 3-indandione, and others. While active against both 3'-processing and strand-transfer reactions, the new compounds, curcumin included, failed to inhibit the HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they specifically inhibited the enzymatic reactions associated with IN, being totally inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA polymerase II) nucleic acid-processing enzymes. On the other hand, title compounds were endowed with remarkable antiproliferative activity, whose potency correlated neither with the presence of catechols (possible source of reactive quinones) nor with inhibition of topoisomerases. The SARs developed for our compounds led to novel findings concerning the molecular determinants of IN inhibitory activity within the class of cinnamoyl-based structures. We hypothesize that these compounds bind to IN featuring the