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Sample records for cui-catalyzed azide-alkyne cycloaddition

  1. Copper(I)-catalyzed azide-alkyne cycloadditions in microflow: catalyst activity, high-T operation, and an integrated continuous copper scavenging unit.

    Science.gov (United States)

    Varas, Alvaro Carlos; Noël, Timothy; Wang, Qi; Hessel, Volker

    2012-09-01

    AVOIDING THE COPPERS: A continuous-flow synthesis for the Cu(I) -catalyzed azide-alkyne cycloaddition reaction using [Cu(phenanthroline)(PPh₃)₂]NO₃ as a homogeneous catalyst is developed (up to 92 % isolated yield). Elevated temperatures allow achieving full conversions and using lower catalyst loadings. Residual copper in the triazole compound is efficiently removed via an inline extraction process, employing aqueous EDTA as a copper scavenger. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Electrochemically Protected Copper(I)-Catalyzed Azide-Alkyne Cycloaddition

    Science.gov (United States)

    Hong, Vu; Udit, Andrew K.; Evans, Richard A.; Finn, M.G.

    2012-01-01

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has found broad application in myriad fields. For the most demanding applications requiring high yields at low substrate concentrations, highly active but air-sensitive copper complexes must be used. We describe here the use of an electrochemical potential to maintain catalysts in the active Cu(I) oxidation state in the presence of air. The simple procedure efficiently achieves excellent yields of CuAAC products involving both small molecule and protein substrates without the use of potentially damaging chemical reducing agents. A new water-soluble carboxylated version of the popular tris(benzyltriazolylmethyl)amine (TBTA) ligand is described. Cyclic voltammetry revealed reversible or quasi-reversible electrochemical redox behavior of copper complexes of the TBTA derivative (2; E1/2 = 60 mV vs. Ag/AgCl), sulfonated bathophenanthroline (3; E1/2 = -60 mV), and sulfonated tris(benzimidazoylmethyl)amine (4; E1/2 ~ -70 mV), and showed catalytic turnover to be rapid relative to the voltammetry time scale. Under the influence of a -200 mV potential established using a reticulated vitreous carbon working electrode, CuSO4 and 3 formed a superior catalyst. Electrochemically-protected bioconjugations in air were performed using bacteriophage Qβ derivatized with azide moieties at surface lysine residues. The complete addressing of more than 600 reactive sites per particle was demonstrated within 12 hours of electrolysis with sub-stoichiometric quantities of Cu•3. PMID:18504727

  3. Electrochemically protected copper(I)-catalyzed azide-alkyne cycloaddition.

    Science.gov (United States)

    Hong, Vu; Udit, Andrew K; Evans, Richard A; Finn, M G

    2008-06-16

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has found broad application in myriad fields. For the most demanding applications that require high yields at low substrate concentrations, highly active but air-sensitive copper complexes must be used. We describe here the use of an electrochemical potential to maintain catalysts in the active Cu(I) oxidation state in the presence of air. This simple procedure efficiently achieves excellent yields of CuAAC products from both small-molecule and protein substrates without the use of potentially damaging chemical reducing agents. A new water-soluble carboxylated version of the popular tris(benzyltriazolylmethyl)amine (TBTA) ligand is also described. Cyclic voltammetry revealed reversible or quasi-reversible electrochemical redox behavior of copper complexes of the TBTA derivative (2; E(1/2)=60 mV vs. Ag/AgCl), sulfonated bathophenanthroline (3; E(1/2)=-60 mV), and sulfonated tris(benzimidazoylmethyl)amine (4; E(1/2) approximately -70 mV), and showed catalytic turnover to be rapid relative to the voltammetry time scale. Under the influence of a -200 mV potential that was established by using a reticulated vitreous carbon working electrode, CuSO4 and 3 formed a superior catalyst. Electrochemically protected bioconjugations in air were performed by using bacteriophage Qbeta that was derivatized with azide moieties at surface lysine residues. Complete derivatization of more than 600 reactive sites per particle was demonstrated within 12 h of electrolysis with substoichiometric quantities of Cu3.

  4. Copper-catalyzed azide alkyne cycloaddition polymer networks

    Science.gov (United States)

    Alzahrani, Abeer Ahmed

    The click reaction concept, introduced in 2001, has since spurred the rapid development and reexamination of efficient, high yield reactions which proceed rapidly under mild conditions. Prior to the discovery of facile copper catalysis in 2002, the thermally activated azide-alkyne or Huisgen cycloaddition reaction was largely ignored following its discovery in large part due to its slow kinetics, requirement for elevated temperature and limited selectivity. Now, arguably, the most prolific and capable of the click reactions, the copper-catalyzed azide alkyne cycloaddition (CuAAC) reaction is extremely efficient and affords exquisite control of the reaction. The orthogonally and chemoselectivity of this reaction enable its wide utility across varied scientific fields. Despite numerous inherent advantages and widespread use for small molecule synthesis and solution-based polymer chemistry, it has only recently and rarely been utilized to form polymer networks. This work focuses on the synthesis, mechanisms, and unique attributes of the CuAAC reaction for the fabrication of functional polymer networks. The photo-reduction of a series of copper(II)/amine complexes via ligand metal charge transfer was examined to determine their relative efficiency and selectivity in catalyzing the CuAAC reaction. The aliphatic amine ligands were used as an electron transfer species to reduce Cu(II) upon irradiation with 365 nm light while also functioning as an accelerating agent and as protecting ligands for the Cu(I) that was formed. Among the aliphatic amines studied, tertiary amines such as triethylamine (TEA), tetramethyldiamine (TMDA), N,N,N',N",N"-pentamethyldiethylenetriamine (PMDTA), and hexamethylenetetramine (HMTETA) were found to be the most effective. The reaction kinetics were accelerated by increasing the PMDETA : Cu(II) ratio with a ratio of ligand to Cu(II) of 4:1 yielding the maximum conversion in the shortest time. The sequential and orthogonal nature of the photo

  5. Copper on Chitosan: A Recyclable Heterogeneous Catalyst for Azide-alkyne Cycloaddition Reactions in Water

    Science.gov (United States)

    Copper sulfate is immobilized over chitosan by simply stirring an aqueous suspension of chitosan in water with copper sulfate; the ensuing catalyst has been utilized for the azide-alkyne cycloaddition in aqueous media and it can be recycled and reused many time without loosing it...

  6. Kinetic resolution of alkyne-substituted quaternary oxindoles via copper catalysed azide-alkyne cycloadditions.

    Science.gov (United States)

    Brittain, William D G; Buckley, Benjamin R; Fossey, John S

    2015-12-18

    The synthesis and kinetic resolution of quaternary oxindoles through copper catalysed azide-alkyne cycloadditions is presented. Selectivity factors (s) up to 22.1 ± 0.5 are reported. Enantioenriched alkynes and triazoles were obtained in ≥80% enantiomeric excess (e.e.).

  7. Pressure-accelerated azide-alkyne cycloaddition: micro capillary versus autoclave reactor performance.

    Science.gov (United States)

    Borukhova, Svetlana; Seeger, Andreas D; Noël, Timothy; Wang, Qi; Busch, Markus; Hessel, Volker

    2015-02-01

    Pressure effects on regioselectivity and yield of cycloaddition reactions have been shown to exist. Nevertheless, high pressure synthetic applications with subsequent benefits in the production of natural products are limited by the general availability of the equipment. In addition, the virtues and limitations of microflow equipment under standard conditions are well established. Herein, we apply novel-process-window (NPWs) principles, such as intensification of intrinsic kinetics of a reaction using high temperature, pressure, and concentration, on azide-alkyne cycloaddition towards synthesis of Rufinamide precursor. We applied three main activation methods (i.e., uncatalyzed batch, uncatalyzed flow, and catalyzed flow) on uncatalyzed and catalyzed azide-alkyne cycloaddition. We compare the performance of two reactors, a specialized autoclave batch reactor for high-pressure operation up to 1800 bar and a capillary flow reactor (up to 400 bar). A differentiated and comprehensive picture is given for the two reactors and the three methods of activation. Reaction speedup and consequent increases in space-time yields is achieved, while the process window for favorable operation to selectively produce Rufinamide precursor in good yields is widened. The best conditions thus determined are applied to several azide-alkyne cycloadditions to widen the scope of the presented methodology. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Accelerating Strain-Promoted Azide-Alkyne Cycloaddition Using Micellar Catalysis.

    Science.gov (United States)

    Anderton, Grant I; Bangerter, Alyssa S; Davis, Tyson C; Feng, Zhiyuan; Furtak, Aric J; Larsen, Jared O; Scroggin, Triniti L; Heemstra, Jennifer M

    2015-08-19

    Bioorthogonal conjugation reactions such as strain-promoted azide-alkyne cycloaddition (SPAAC) have become increasingly popular in recent years, as they enable site-specific labeling of complex biomolecules. However, despite a number of improvements to cyclooctyne design, reaction rates for SPAAC remain significantly lower than those of the related copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Here we explore micellar catalysis as a means to increase reaction rate between a cyclooctyne and hydrophobic azide. We find that anionic and cationic surfactants provide the most efficient catalysis, with rate enhancements of up to 179-fold for reaction of benzyl azide with DIBAC cyclooctyne. Additionally, we find that the presence of surfactant can provide up to 51-fold selectivity for reaction with a hydrophobic over hydrophilic azide. A more modest, but still substantial, 11-fold rate enhancement is observed for micellar catalysis of the reaction between benzyl azide and a DIBAC-functionalized DNA sequence, demonstrating that micellar catalysis can be successfully applied to hydrophilic biomolecules. Together, these results demonstrate that micellar catalysis can provide higher conjugation yields in reduced time when using hydrophobic SPAAC reagents.

  9. Multifunctional Giant Amphiphiles via simultaneous copper(I)-catalyzed azide-alkyne cycloaddition and living radical polymerization.

    Science.gov (United States)

    Daskalaki, Eleftheria; Le Droumaguet, Benjamin; Gérard, David; Velonia, Kelly

    2012-02-01

    A novel class of chemically addressable, multifunctional Giant Amphiphiles was synthesized in excellent yields and polydispersity following simultaneous or sequential living radical polymerization and the click, copper(I)-catalysed azide-alkyne cycloaddition (CuAAC). This new approach allows chemical tailoring of the biomacromolecules and in situ formation of nanocontainers. This journal is © The Royal Society of Chemistry 2012

  10. Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions.

    Science.gov (United States)

    Zhang, Xiaoguang; Liu, Peiye; Zhu, Lei

    2016-12-09

    This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as "privileged" azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under both copper(II)- (via an induction period) and copper(I)-catalyzed conditions. The first type of the alkynes bears relatively acidic ethynyl C-H bonds, while the second type contains an N-(triazolylmethyl)propargylic moiety that produces a self-accelerating effect. The rankings of reactivity under both copper(II)- and copper(I)-catalyzed conditions are provided. The observations on how other reaction parameters such as accelerating ligand, reducing agent, or identity of azide alter the relative reactivity of alkynes are described and, to the best of our ability, explained.

  11. Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions

    Directory of Open Access Journals (Sweden)

    Xiaoguang Zhang

    2016-12-01

    Full Text Available This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as “privileged” azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under both copper(II- (via an induction period and copper(I-catalyzed conditions. The first type of the alkynes bears relatively acidic ethynyl C-H bonds, while the second type contains an N-(triazolylmethylpropargylic moiety that produces a self-accelerating effect. The rankings of reactivity under both copper(II- and copper(I-catalyzed conditions are provided. The observations on how other reaction parameters such as accelerating ligand, reducing agent, or identity of azide alter the relative reactivity of alkynes are described and, to the best of our ability, explained.

  12. Copper catalysed azide-alkyne cycloaddition (CuAAC) in liquid ammonia.

    Science.gov (United States)

    Ji, Pengju; Atherton, John H; Page, Michael I

    2012-10-21

    Copper(I) catalysed azide-alkyne cycloaddition reactions (CuAAC) occur smoothly in liquid ammonia (LNH(3)) at room temperature to give exclusively 1,4-substituted 1,2,3-triazoles with excellent yields (up to 99%). The CuAAC reactions in liquid ammonia require relatively small amounts of copper(I) catalyst (0.5 mole%) compared with that in conventional solvents. The product can be obtained conveniently by simply evaporation of ammonia, indicating its potential application in industry. The rate of the CuAAC reaction in liquid ammonia shows a second order dependence on the copper(I) concentration and the reaction occurs only with terminal alkynes. Deuterium exchange experiments with phenyl acetylene-d(1) show that the acidity of the alkyne is increased at least 1000-fold with catalytic amounts of copper(I) in liquid ammonia. The mechanism of the CuAAC reaction in liquid ammonia is discussed.

  13. Efficient and Site-specific Antibody Labeling by Strain-promoted Azide-alkyne Cycloaddition.

    Science.gov (United States)

    Kim, Sanggil; Ko, Wooseok; Park, Hyunji; Lee, Hyun Soo

    2016-12-23

    There are currently many chemical tools available to introduce chemical probes into proteins to study their structure and function. A useful method is protein conjugation by genetically introducing an unnatural amino acid containing a bioorthogonal functional group. This report describes a detailed protocol for site-specific antibody conjugation. The protocol includes experimental details for the genetic incorporation of an azide-containing amino acid, and the conjugation reaction by strain-promoted azide-alkyne cycloaddition (SPAAC). This strain-promoted reaction proceeds by simple mixing of the reacting molecules at physiological pH and temperature, and does not require additional reagents such as copper(I) ions and copper-chelating ligands. Therefore, this method would be useful for general protein conjugation and development of antibody drug conjugates (ADCs).

  14. Selection of Natural Peptide Ligands for Copper-Catalyzed Azide-Alkyne Cycloaddition Catalysis.

    Science.gov (United States)

    Aioub, Allison G; Dahora, Lindsay; Gamble, Kelly; Finn, M G

    2017-06-21

    The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a powerful tool for making connections in both organic reactions and biological systems. However, the use of this ligation process in living cells is limited by the toxicity associated with unbound copper ions. As an initial attempt to create peptide-based accelerating ligands capable of cellular expression, we performed synthesis and selection for such species on solid-phase synthesis beads bearing both candidate ligand and alkyne substrate. A simple histidine-containing motif (HXXH) was identified, and found after solution-phase optimization to produce single-turnover systems showing moderate rate acceleration over the ligand-free reaction. CuAAC reaction rates and yields for different alkynes were found to respond to the peptide ligands, demonstrating a substrate scope beyond what was used for the selection steps, but also illustrating the potential difficulty in evolving a general CuAAC catalyst.

  15. Relative performance of alkynes in copper-catalyzed azide-alkyne cycloaddition.

    Science.gov (United States)

    Kislukhin, Alexander A; Hong, Vu P; Breitenkamp, Kurt E; Finn, M G

    2013-04-17

    Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has found numerous applications in a variety of fields. We report here only modest differences in the reactivity of various classes of terminal alkynes under typical bioconjugative and preparative organic conditions. Propargyl compounds represent an excellent combination of azide reactivity, ease of installation, and cost. Electronically activated propiolamides are slightly more reactive, at the expense of increased propensity for Michael addition. Certain alkynes, including tertiary propargyl carbamates, are not suitable for bioconjugation due to copper-induced fragmentation. A fluorogenic probe based on such reactivity is available in one step from rhodamine 110 and can be useful for optimization of CuAAC conditions.

  16. Hybrid NS ligands supported Cu(I)/(II) complexes for azide-alkyne cycloaddition reactions.

    Science.gov (United States)

    Bai, Shi-Qiang; Jiang, Lu; Zuo, Jing-Lin; Hor, T S Andy

    2013-08-21

    Three copper complexes of nitrogen-sulfur donor ligands, [CuBr₂(L1)] (1), [CuCl₂(L2)₂] (2) and [Cu₂I₂(L3)]n (3) (L1 = bis(2-cyclohexylsulfanylethyl)amine, L2 = 2-(benzylsulfanylmethyl)pyridine and L3 = 2-(4-pyridylsulfanylmethyl)pyridine), have been synthesized and characterized by single-crystal X-ray diffraction (XRD), powder XRD and TGA analysis. Complexes 1 and 2 are mononuclear Cu(II) complexes and are EPR active with distorted square-pyramidal and octahedral geometry, respectively. Complex 3 is a two-dimensional tetrahedral Cu(I) coordination polymer with 16- and 20-membered metallocycles. These complexes show good catalytic activities for one-pot azide-alkyne cycloaddition reactions in CH₃OH-H₂O.

  17. Copper-catalyzed tandem azide-alkyne cycloaddition, Ullmann type C-N coupling, and intramolecular direct arylation.

    Science.gov (United States)

    Pericherla, Kasiviswanadharaju; Jha, Amitabh; Khungar, Bharti; Kumar, Anil

    2013-09-06

    A ligand-free copper-catalyzed tandem azide-alkyne cycloaddition (CuAAC), Ullmann-type C-N coupling, and intramolecular direct arylation has been described. The designed strategy resulted in the synthesis of a novel trazole-fused azaheterocycle framework. The reaction gave good yields (59-77%) of 1,2,3-triazole-fused imidazo[1,2-a]pyridines in a single step.

  18. Ligand-assisted, copper(II) acetate-accelerated azide-alkyne cycloaddition.

    Science.gov (United States)

    Michaels, Heather A; Zhu, Lei

    2011-10-04

    Polytriazole ligands such as the widely used tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine (TBTA), are shown to assist copper(II) acetate-mediated azide-alkyne cycloaddition (AAC) reactions that involve nonchelating azides. Tris(2-{4-[(dimethylamino)methyl]-1H-1,2,3-traizol-1-yl}ethyl)amine (DTEA) outperforms TBTA in a number of reactions. The satisfactory solubility of DTEA in a wide range of polar and nonpolar solvents, including water and toluene, renders it advantageous under copper(II) acetate-mediated conditions. The copper(II) acetate-mediated formation of the three triazolyl groups in a tris(triazolyl)-based ligand occurs sequentially with an inhibitory effect in the last step. The kinetic investigations of the ligand-assisted reactions reveal an interesting mechanistic dependence on the relative affinity of azide and alkyne to copper (II). In addition to expanding the scope of the copper(II) acetate-mediated AAC reactions to include nonchelating azides, this work offers evidence for the mechanistic synergy between the title reaction and the alkyne oxidative homocoupling reaction. The elucidation of the structural details of the polytriazole-ligand-bound reactive species in copper(I/II)-mediated AAC reactions, however, awaits further characterization of the metal coordination chemistry of polytriazole ligands. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Sulfated ligands for the copper(I)-catalyzed azide-alkyne cycloaddition.

    Science.gov (United States)

    Wang, Wei; Hong, Senglian; Tran, Andrew; Jiang, Hao; Triano, Rebecca; Liu, Yi; Chen, Xing; Wu, Peng

    2011-10-04

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), the prototypical reaction of click chemistry, is accelerated by tris(triazolylmethyl)amine-based ligands. Herein, we compare two new ligands in this family--3-[4-({bis[(1-tert-butyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propanol (BTTP) and the corresponding sulfated ligand 3-[4-({bis[(1-tert-butyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propyl hydrogen sulfate (BTTPS)--for three bioconjugation applications: 1) labeling of alkyne-tagged glycoproteins in crude cell lysates, 2) labeling of alkyne- or azide-tagged glycoproteins on the surface of live mammalian cells, and 3) labeling of azides in surface proteins of live Escherichia coli. Although BTTPS exhibits faster kinetics than BTTP in accelerating the CuAAC reaction in in vitro kinetic measurements, its labeling efficiency is slightly lower than BTTP in modifying biomolecules with a significant amount of negative charges due to electrostatic repulsion. Nevertheless, the negative charge conferred by the sulfate at physiological conditions significantly reduced the cellular internalization of the coordinated copper(I), thus making BTTPS-Cu(I) a better choice for live-cell labeling. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Functionalisation of lanthanide complexes via microwave-enhanced Cu(I)-catalysed azide-alkyne cycloaddition.

    Science.gov (United States)

    Szíjjártó, Csongor; Pershagen, Elias; Borbas, K Eszter

    2012-07-07

    Cu(I)-catalysed azide-alkyne cycloaddition reactions were used to functionalise lanthanide(III)-complexes (Ln; La, Eu and Tb) incorporating alkyne or azide reactive groups. Microwave irradiation significantly accelerated the reactions, enabling full conversion to the triazole products in some cases in 5 min. Alkyl and aryl azides and alkyl and aryl alkynes could all serve as coupling partners. These reaction conditions proved efficient for cyclen-tricarboxylates and previously unreactive cyclen-tris-primary amide chelates. The synthesis of heterobimetallic (Eu/Tb, EuTb17 and Eu/La, EuLa17) and heterotrimetallic (Eu/La/Eu) complexes was achieved in up to 60% isolated yield starting from coumarin 2-appended alkynyl complexes Tb16 or La16 and an azido-Eu complex Eu4, and bis-alkynyl La-complex La5 and Eu4, respectively. EuTb17 displayed dual Eu(III) and Tb(III)-emission upon antenna-centred excitation.

  1. On the Mechanism of Copper(I)-Catalyzed Azide-Alkyne Cycloaddition.

    Science.gov (United States)

    Zhu, Lei; Brassard, Christopher J; Zhang, Xiaoguang; Guha, P M; Clark, Ronald J

    2016-06-01

    The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction regiospecifically produces 1,4-disubstituted-1,2,3-triazole molecules. This heterocycle formation chemistry has high tolerance to reaction conditions and substrate structures. Therefore, it has been practiced not only within, but also far beyond the area of heterocyclic chemistry. Herein, the mechanistic understanding of CuAAC is summarized, with a particular emphasis on the significance of copper/azide interactions. Our analysis concludes that the formation of the azide/copper(I) acetylide complex in the early stage of the reaction dictates the reaction rate. The subsequent triazole ring-formation step is fast and consequently possibly kinetically invisible. Therefore, structures of substrates and copper catalysts, as well as other reaction variables that are conducive to the formation of the copper/alkyne/azide ternary complex predisposed for cycloaddition would result in highly efficient CuAAC reactions. Specifically, terminal alkynes with relatively low pKa values and an inclination to engage in π-backbonding with copper(I), azides with ancillary copper-binding ligands (aka chelating azides), and copper catalysts that resist aggregation, balance redox activity with Lewis acidity, and allow for dinuclear cooperative catalysis are favored in CuAAC reactions. Brief discussions on the mechanistic aspects of internal alkyne-involved CuAAC reactions are also included, based on the relatively limited data that are available at this point. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Fluorescent labelling of in situ hybridisation probes through the copper-catalysed azide-alkyne cycloaddition reaction.

    Science.gov (United States)

    Hesse, Susann; Manetto, Antonio; Cassinelli, Valentina; Fuchs, Jörg; Ma, Lu; Raddaoui, Nada; Houben, Andreas

    2016-09-01

    In situ hybridisation is a powerful tool to investigate the genome and chromosome architecture. Nick translation (NT) is widely used to label DNA probes for fluorescence in situ hybridisation (FISH). However, NT is limited to the use of long double-stranded DNA and does not allow the labelling of single-stranded and short DNA, e.g. oligonucleotides. An alternative technique is the copper(I)-catalysed azide-alkyne cycloaddition (CuAAC), at which azide and alkyne functional groups react in a multistep process catalysed by copper(I) ions to give 1,4-distributed 1,2,3-triazoles at a high yield (also called 'click reaction'). We successfully applied this technique to label short single-stranded DNA probes as well as long PCR-derived double-stranded probes and tested them by FISH on plant chromosomes and nuclei. The hybridisation efficiency of differently labelled probes was compared to those obtained by conventional labelling techniques. We show that copper(I)-catalysed azide-alkyne cycloaddition-labelled probes are reliable tools to detect different types of repetitive sequences on chromosomes opening new promising routes for the detection of single copy gene. Moreover, a combination of FISH using such probes with other techniques, e.g. immunohistochemistry (IHC) and cell proliferation assays using 5-ethynyl-deoxyuridine, is herein shown to be easily feasible.

  3. Chelation-assisted, copper(II)-acetate-accelerated azide-alkyne cycloaddition.

    Science.gov (United States)

    Kuang, Gui-Chao; Michaels, Heather A; Simmons, J Tyler; Clark, Ronald J; Zhu, Lei

    2010-10-01

    We described in a previous communication a variant of the popular Cu(I)-catalyzed azide-alkyne cycloaddition (AAC) process where 5 mol % of Cu(OAc)(2) in the absence of any added reducing agent is sufficient to enable the reaction. 2-Picolylazide (1) and 2-azidomethylquinoline (2) were found to be by far the most reactive carbon azide substrates that convert to 1,2,3-triazoles in as short as a few minutes under the discovered conditions. We hypothesized that the abilities of 1 and 2 to chelate Cu(II) contribute significantly to the observed high reaction rates. The current work examines the effect of auxiliary ligands near the azido group other than pyridyl for Cu(II) on the efficiency of the Cu(OAc)(2)-accelerated AAC reaction. The carbon azides capable of binding to the catalytic copper center at the alkylated azido nitrogen in a chelatable fashion were indeed shown to be superior substrates under the reported conditions. The chelation between carbon azide 11 and Cu(II) was demonstrated in an X-ray single-crystal structure. In a limited set of examples, the ligand tris(benzyltriazolylmethyl)amine (TBTA), developed by Fokin et al. for assisting the original Cu(I)-catalyzed AAC reactions, also dramatically enhances the Cu(OAc)(2)-accelerated AAC reactions involving nonchelating azides. This observation leads to the hypothesis of an additional effect of chelating azides on the efficiencies of Cu(OAc)(2)-accelerated AAC reactions, which is to facilitate the rapid reduction of Cu(II) to highly catalytic Cu(I) species. Mechanistic studies on the AAC reactions with particular emphasis on the role of carbon azide/copper interactions will be conducted based on the observations reported in this work. Finally, the immediate utility of the product 1,2,3-triazole molecules derived from chelating azides as multidentate metal coordination ligands is demonstrated. The resulting triazolyl-containing ligands are expected to bind with transition metal ions via the N(2) nitrogen of

  4. Traceless Azido Linker for the Solid-Phase Synthesis of NH-1,2,3-Triazoles via Cu-Catalyzed Azide-Alkyne Cycloaddition Reactions

    DEFF Research Database (Denmark)

    Cohrt, Anders Emil; Jensen, Jakob Feldthusen; Nielsen, Thomas Eiland

    2010-01-01

    A broadly useful acid-labile traceless azido linker for the solid-phase synthesis of NH-1,2,3-triazoles is presented. A variety of alkynes were efficiently immobilized on a range of polymeric supports by Cu(I)-mediated azide-alkyne cycloadditions. Supported triazoles showed excellent compatibility...

  5. Chelation-Assisted, Copper(II) Acetate-Accelerated Azide-Alkyne Cycloaddition

    Science.gov (United States)

    Kuang, Gui-Chao; Michaels, Heather A.; Simmons, J. Tyler; Clark, Ronald J.; Zhu, Lei

    2010-01-01

    We described in a previous communication (ref. 13) a variant of the popular CuI-catalyzed azide-alkyne cycloaddition (AAC) process where 5 mol% Cu(OAc)2 in the absence of any added reducing agent is sufficient to enable the reaction. 2-Picolylazide (1) and 2-azidomethylquinoline (2) were found to be by far the most reactive carbon azide substrates that convert to 1,2,3-triazoles in as short as a few minutes under the discovered conditions. We hypothesized that the abilities of 1 and 2 to chelate CuII contribute significantly to the observed high reaction rates. The current work examines the effect of auxiliary ligands near the azido group other than pyridyl for CuII on the efficiency of the Cu(OAc)2-accelerated AAC reaction. The carbon azides capable of binding to the catalytic copper center at the alkylated azido nitrogen in a chelatable fashion were indeed shown to be superior substrates under the reported conditions. The chelation between carbon azide 11 and CuII was demonstrated in an X-ray single crystal structure. In a limited set of examples, the ligand tris(benzyltriazolylmethyl)amine (TBTA), developed by Fokin et al. for assisting the original CuI-catalyzed AAC reactions (ref. 8), also dramatically enhances the Cu(OAc)2-accelerated AAC reactions involving non-chelating azides. This observation leads to the hypothesis of an additional effect of chelating azides on the efficiencies of Cu(OAc)2-accelerated AAC reactions, which is to facilitate the rapid reduction of CuII to highly catalytic CuI species. Mechanistic studies on the AAC reactions with particular emphasis on the role of carbon azide/copper interactions will be conducted based on the observations reported in this work. Finally, the immediate utility of the product 1,2,3-triazole molecules derived from chelating azides as multidentate metal coordination ligands is demonstrated. The resulting triazolyl-containing ligands are expected to bind with transition metal ions via the N(2) nitrogen of the 1

  6. Tricks with clicks: modification of peptidomimetic oligomers via copper-catalyzed azide-alkyne [3 + 2] cycloaddition.

    Science.gov (United States)

    Holub, Justin M; Kirshenbaum, Kent

    2010-04-01

    This tutorial review examines recent developments involving use of Copper-catalyzed Azide-Alkyne [3 + 2] Cycloaddition (CuAAC) reactions in the synthesis, modification, and conformational control of peptidomimetic oligomers. CuAAC reactions have been used to address a variety of objectives including: (i) ligation of peptidomimetic oligomers; (ii) synthesis of ordered "foldamer" architectures; (iii) conjugation of ligands to peptidomimetic scaffolds; and (iv) macrocyclization of peptidomimetics using triazole linkages as conformational constraints. Variations in synthesis protocols, such as the use of different solvent systems, temperatures and copper species are evaluated herein to present a range of variables for the optimization of CuAAC reactions. The overall objectives of these studies are assessed to highlight the widespread applications of the products, which range from bioactive ligands to new materials.

  7. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(I) acetylides.

    Science.gov (United States)

    Hein, Jason E; Fokin, Valery V

    2010-04-01

    Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(I) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science.

  8. Azide-alkyne cycloaddition for universal post-synthetic modifications of nucleic acids and effective synthesis of bioactive nucleic acid conjugates.

    Science.gov (United States)

    Su, Yu-Chih; Lo, Yu-Lun; Hwang, Chi-Ching; Wang, Li-Fang; Wu, Min Hui; Wang, Eng-Chi; Wang, Yun-Ming; Wang, Tzu-Pin

    2014-09-14

    The regioselective post-synthetic modifications of nucleic acids are essential to studies of these molecules for science and applications. Here we report a facile universal approach by harnessing versatile phosphoramidation reactions to regioselectively incorporate alkynyl/azido groups into post-synthetic nucleic acids primed with phosphate at the 5' termini. With and without the presence of copper, the modified nucleic acids were subjected to azide-alkyne cycloaddition to afford various nucleic acid conjugates including a peptide-oligonucleotide conjugate (POC) with high yield. The POC was inoculated with human A549 cells and demonstrated excellent cell-penetrating ability despite cell deformation caused by a small amount of residual copper chelated to the POC. The combination of phosphoramidation and azide-alkyne cycloaddition reactions thus provides a universal regioselective strategy to post-synthetically modify nucleic acids. This study also explicated the toxicity of residual copper in synthesized bioconjugates destined for biological systems.

  9. Solvent effect on copper-catalyzed azide-alkyne cycloaddition (CuAAC): synthesis of novel triazolyl substituted quinolines as potential anticancer agents.

    Science.gov (United States)

    Ellanki, Amarender Reddy; Islam, Aminul; Rama, Veera Swamy; Pulipati, Ranga Prasad; Rambabu, D; Krishna, G Rama; Reddy, C Malla; Mukkanti, K; Vanaja, G R; Kalle, Arunasree M; Kumar, K Shiva; Pal, Manojit

    2012-05-15

    A regioselective route to novel mono triazolyl substituted quinolines has been developed via copper-catalyzed azide-alkyne cycloaddition (CuAAC) of 2,4-diazidoquinoline with terminal alkynes in DMF. The reaction provided bis triazolyl substituted quinolines when performed in water in the presence of Et(3)N. A number of the compounds synthesized showed promising anti-proliferative properties when tested in vitro especially against breast cancer cells. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Chemically directed assembly of photoactive metal oxide nanoparticle heterojunctions via the copper-catalyzed azide-alkyne cycloaddition "click" reaction.

    Science.gov (United States)

    Cardiel, Allison C; Benson, Michelle C; Bishop, Lee M; Louis, Kacie M; Yeager, Joseph C; Tan, Yizheng; Hamers, Robert J

    2012-01-24

    Metal oxides play a key role in many emerging applications in renewable energy, such as dye-sensitized solar cells and photocatalysts. Because the separation of charge can often be facilitated at junctions between different materials, there is great interest in the formation of heterojunctions between metal oxides. Here, we demonstrate use of the copper-catalyzed azide-alkyne cycloaddition reaction, widely referred to as "click" chemistry, to chemically assemble photoactive heterojunctions between metal oxide nanoparticles, using WO(3) and TiO(2) as a model system. X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopy verify the nature and selectivity of the chemical linkages, while scanning electron microscopy reveals that the TiO(2) nanoparticles form a high-density, conformal coating on the larger WO(3) nanoparticles. Time-resolved surface photoresponse measurements show that the resulting dyadic structures support photoactivated charge transfer, while measurements of the photocatalytic degradation of methylene blue show that chemical grafting of TiO(2) nanoparticles to WO(3) increases the photocatalytic activity compared with the bare WO(3) film.

  11. Solution-phase parallel synthesis of ruxolitinib-derived Janus kinase inhibitors via copper-catalyzed azide-alkyne cycloaddition.

    Science.gov (United States)

    Gehringer, Matthias; Forster, Michael; Laufer, Stefan A

    2015-01-12

    A solution-phase parallel synthesis of triazole-derived ruxolitinib analogues was developed in the current study. The method employs copper-catalyzed azide-alkyne cycloaddition to build up the central triazole template. Product isolation by precipitation and centrifugation is straightforward and yields high purity compounds suited for biological profiling. A simple protocol for accessing the terminal alkyne precursors in high yields was established and a library of ruxolitinib-like triazoles featuring diverse functional groups was prepared. In addition, a model for the binding mode of ruxolitinib to Janus kinase (JAK) 2 is proposed. In contrast to previous models, the pose explains the compound selectivity for JAK1/JAK2 and is in accordance with published structure-activity data. On this basis, a structure-based design hypothesis for inverting the selectivity profile of ruxolitinib is deduced. Application of this strategy identified a moderately potent JAK3 inhibitor (35 nM) with high selectivity against other JAKs, potentially exploiting a covalent binding mode.

  12. Development and Applications of the Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC as a Bioorthogonal Reaction

    Directory of Open Access Journals (Sweden)

    Li Li

    2016-10-01

    Full Text Available The emergence of bioorthogonal reactions has greatly broadened the scope of biomolecule labeling and detecting. Of all the bioorthogonal reactions that have been developed, the copper-catalyzed azide-alkyne cycloaddition (CuAAC is the most widely applied one, mainly because of its relatively fast kinetics and high efficiency. However, the introduction of copper species to in vivo systems raises the issue of potential toxicity. In order to reduce the copper-induced toxicity and further improve the reaction kinetics and efficiency, different strategies have been adopted, including the development of diverse copper chelating ligands to assist the catalytic cycle and the development of chelating azides as reagents. Up to now, the optimization of CuAAC has facilitated its applications in labeling and identifying either specific biomolecule species or on the omics level. Herein, we mainly discuss the efforts in the development of CuAAC to better fit the bioorthogonal reaction criteria and its bioorthogonal applications both in vivo and in vitro.

  13. Development and Applications of the Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) as a Bioorthogonal Reaction.

    Science.gov (United States)

    Li, Li; Zhang, Zhiyuan

    2016-10-24

    The emergence of bioorthogonal reactions has greatly broadened the scope of biomolecule labeling and detecting. Of all the bioorthogonal reactions that have been developed, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) is the most widely applied one, mainly because of its relatively fast kinetics and high efficiency. However, the introduction of copper species to in vivo systems raises the issue of potential toxicity. In order to reduce the copper-induced toxicity and further improve the reaction kinetics and efficiency, different strategies have been adopted, including the development of diverse copper chelating ligands to assist the catalytic cycle and the development of chelating azides as reagents. Up to now, the optimization of CuAAC has facilitated its applications in labeling and identifying either specific biomolecule species or on the omics level. Herein, we mainly discuss the efforts in the development of CuAAC to better fit the bioorthogonal reaction criteria and its bioorthogonal applications both in vivo and in vitro.

  14. Lignocellulosic Micro- and Nanomaterials as Copper Frames for the Evaluation of the Copper(I-Catalyzed Azide-Alkyne Cycloaddition

    Directory of Open Access Journals (Sweden)

    Charles W. Owens

    2017-01-01

    Full Text Available Copper was immobilized onto carboxymethyl cellulose, nanofibrillated cellulose, TEMPO-nanofibrillated cellulose, and lignin. The lignocellulosic frames were used with the aim of providing an effective support for catalyst copper and allowing its further reutilization. Each organic support was successful and effective in the coupling of copper with the exception of lignin. These complexes were used as heterogeneous catalysts to produce 1-benzyl-4-phenyl-1H-[1,2,3]-triazole from the copper(I-catalyzed azide-alkyne cycloaddition (CuAAC between benzyl azide and phenylacetylene. Each reaction was carried out in water and acetonitrile. Those performed in water were completed in 15 minutes while those done in acetonitrile were allowed to react overnight, reaching completion in less than 20 hours. The yields for Cu-CMC resulted in over 90% for those reactions performed in acetonitrile. All catalysts were easy to recover except Cu-lignin which could not be filtered or extracted from the reaction effluent.

  15. Injectable hyaluronic acid/poly(ethylene glycol) hydrogels crosslinked via strain-promoted azide-alkyne cycloaddition click reaction.

    Science.gov (United States)

    Fu, Shuangli; Dong, Hui; Deng, Xueyi; Zhuo, Renxi; Zhong, Zhenlin

    2017-08-01

    This paper reports injectable hyaluronic acid (HA)-based hydrogels crosslinked with azide-modified poly(ethylene glycol) (PEG) via the strain-promoted azide-alkyne cycloaddition (SPAAC) between cyclooctyne and azide groups. Cyclooctyne-modified HA (Cyclooctyne-HA) is prepared by the reaction of HA with 2-(aminoethoxy)cyclooctyne. To crosslink the modified HA, quadruply azide-terminated poly(ethylene glycol) (Azide-PEG) is designed and prepared. The mixture of Cyclooctyne-HA and Azide-PEG gelates in a few minutes to form a strong HA-PEG hydrogel. The hydrogel has fast gelation time, good strength, and slow degradation rate, because of the high reactivity of SPAAC, high crosslinking density originated from the quadruply-substituted Azide-PEG, and the good stability of the crosslinking amide bonds. In vitro cell culturing within the hydrogel demonstrated an excellent cell-compatibility. The bioorthogonality of SPAAC makes the hydrogel injectable. With good mechanical properties and biocompatibility, the hydrogel would be useful in a wide range of applications such as injection filling materials for plastic surgery. Copyright © 2017. Published by Elsevier Ltd.

  16. A concomitant allylic azide rearrangement/intramolecular azide-alkyne cycloaddition sequence.

    Science.gov (United States)

    Vekariya, Rakesh H; Liu, Ruzhang; Aubé, Jeffrey

    2014-04-04

    An intramolecular Huisgen cycloaddition of an interconverting set of isomeric allylic azides with alkynes affords substituted triazoles in high yield. The stereoisomeric vinyl-substituted triazoloxazines formed depend on the rate of cycloaddition of the different allylic azide precursors when the reaction is carried out under thermal conditions. In contrast, dimerized macrocyclic products were obtained when the reaction was done using copper(I)-catalyzed conditions, demonstrating the ability to control the reaction products through changing conditions.

  17. Copper-free azide-alkyne cycloaddition of targeting peptides to porous silicon nanoparticles for intracellular drug uptake.

    Science.gov (United States)

    Wang, Chang-Fang; Mäkilä, Ermei M; Kaasalainen, Martti H; Liu, Dongfei; Sarparanta, Mirkka P; Airaksinen, Anu J; Salonen, Jarno J; Hirvonen, Jouni T; Santos, Hélder A

    2014-01-01

    Porous silicon (PSi) has been demonstrated as a promising drug delivery vector for poorly water-soluble drugs. Here, a simple and efficient method based on copper-free click chemistry was used to introduce targeting moieties to PSi nanoparticles in order to enhance the intracellular uptake and tumor specific targeting hydrophobic drug delivery. Two RGD derivatives (RGDS and iRGD) with azide-terminated groups were conjugated to bicyclononyne-functionalized PSi nanoparticles via copper-free azide-alkyne cycloaddition. The surface functionalization was performed in aqueous solution at 37 °C for 30 min resulting in conjugation efficiencies of 15.2 and 3.4% (molar ratios) and the nanoparticle size increased from 165.6 nm to 179.6 and 188.8 nm for RGDS and iRGD, respectively. The peptides modification enhanced the cell uptake efficiency of PSi nanoparticles in EA.hy926 cells. PSi-RGDS and PSi-iRGD nanoparticles loaded with sorafenib showed a similar trend for the in vitro antiproliferation activity compared to sorafenib dissolved in dimethyl sulfoxide. Furthermore, sorafenib-loaded PSi-RGDS deliver the drug intracellulary efficiently due to the higher surface conjugation ratio, resulting in enhanced in vitro antiproliferation effect. Our results highlight the surface functionalization methodology for PSi nanoparticles applied here as a universal method to introduce functional moieties onto the surface of PSi nanoparticles and demonstrate their potential active targeting properties for anticancer drug delivery.

  18. Azide-Alkyne Huisgen [3+2] Cycloaddition Using CuO Nanoparticles

    Directory of Open Access Journals (Sweden)

    Hyunjoon Song

    2012-11-01

    Full Text Available Recent developments in the synthesis of CuO nanoparticles (NPs and their application to the [3+2] cycloaddition of azides with terminal alkynes are reviewed. With respect to the importance of click chemistry, CuO hollow NPs, CuO hollow NPs on acetylene black, water-soluble double-hydrophilic block copolymer (DHBC nanoreactors and ZnO–CuO hybrid NPs were synthesized. Non-conventional energy sources such as microwaves and ultrasound were also applied to these click reactions, and good catalytic activity with high regioselectivity was observed. CuO hollow NPs on acetylene black can be recycled nine times without any loss of activity, and water-soluble DHBC nanoreactors have been developed for an environmentally friendly process.

  19. The mechanism of copper-catalyzed azide-alkyne cycloaddition reaction: a quantum mechanical investigation.

    Science.gov (United States)

    Ozen, Cihan; Tüzün, Nurcan Ş

    2012-04-01

    In this study, the mechanism of CuAAC reaction and the structure of copper acetylides have been investigated with quantum mechanical methods, namely B3LYP/6-311+G(d,p). A series of possible copper-acetylide species which contain up to four copper atoms and solvent molecules as ligand has been evaluated and a four-copper containing copper-acetylide, M1A, was proposed more likely to form based on its thermodynamic stability. The reaction has been modeled with a representative simple alkyne and a simple azide to concentrate solely on the electronic effects of the mechanism. Later, the devised mechanism has been applied to a real system, namely to the reaction of 2-azido-1,1,1-trifluoroethane and ethynylbenzene in the presence of copper. The copper catalyst transforms the concerted uncatalyzed reaction to a stepwise process and lowers the activation barrier. The pre-reactive complexation of the negatively charged secondary nitrogen of azide and the positively charged copper of copper-acetylide brings the azide and the alkyne to a suitable geometry for cycloaddition to take place. The calculated activation barrier difference between the catalyzed and the uncatalyzed reactions is consistent with faster and the regioselective synthesis of triazole product. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Experimental investigation on the mechanism of chelation-assisted, copper(II) acetate-accelerated azide-alkyne cycloaddition.

    Science.gov (United States)

    Kuang, Gui-Chao; Guha, Pampa M; Brotherton, Wendy S; Simmons, J Tyler; Stankee, Lisa A; Nguyen, Brian T; Clark, Ronald J; Zhu, Lei

    2011-09-07

    A mechanistic model is formulated to account for the high reactivity of chelating azides (organic azides capable of chelation-assisted metal coordination at the alkylated azido nitrogen position) and copper(II) acetate (Cu(OAc)(2)) in copper(II)-mediated azide-alkyne cycloaddition (AAC) reactions. Fluorescence and (1)H NMR assays are developed for monitoring the reaction progress in two different solvents, methanol and acetonitrile. Solvent kinetic isotopic effect and premixing experiments give credence to the proposed different induction reactions for converting copper(II) to catalytic copper(I) species in methanol (methanol oxidation) and acetonitrile (alkyne oxidative homocoupling), respectively. The kinetic orders of individual components in a chelation-assisted, copper(II)-accelerated AAC reaction are determined in both methanol and acetonitrile. Key conclusions resulting from the kinetic studies include (1) the interaction between copper ion (either in +1 or +2 oxidation state) and a chelating azide occurs in a fast, pre-equilibrium step prior to the formation of the in-cycle copper(I)-acetylide, (2) alkyne deprotonation is involved in several kinetically significant steps, and (3) consistent with prior experimental and computational results by other groups, two copper centers are involved in the catalysis. The X-ray crystal structures of chelating azides with Cu(OAc)(2) suggest a mechanistic synergy between alkyne oxidative homocoupling and copper(II)-accelerated AAC reactions, in which both a bimetallic catalytic pathway and a base are involved. The different roles of the two copper centers (a Lewis acid to enhance the electrophilicity of the azido group and a two-electron reducing agent in oxidative metallacycle formation, respectively) in the proposed catalytic cycle suggest that a mixed valency (+2 and +1) dinuclear copper species be a highly efficient catalyst. This proposition is supported by the higher activity of the partially reduced Cu(OAc)(2) in

  1. Synthesis of steroid-ferrocene conjugates of steroidal 17-carboxamides via a palladium-catalyzed aminocarbonylation--copper-catalyzed azide-alkyne cycloaddition reaction sequence.

    Science.gov (United States)

    Szánti-Pintér, Eszter; Balogh, János; Csók, Zsolt; Kollár, László; Gömöry, Agnes; Skoda-Földes, Rita

    2011-11-01

    Steroids with the 17-iodo-16-ene functionality were converted to ferrocene labeled steroidal 17-carboxamides via a two step reaction sequence. The first step involved the palladium-catalyzed aminocarbonylation of the alkenyl iodides with prop-2-yn-1-amine as the nucleophile in the presence of the Pd(OAc)(2)/PPh(3) catalyst system. In the second step, the product N-(prop-2-ynyl)-carboxamides underwent a facile azide-alkyne cycloaddition with ferrocenyl azides in the presence of CuSO(4)/sodium ascorbate to produce the steroid-ferrocene conjugates. The new compounds were obtained in good yield and were characterized by (1)H and (13)C NMR, IR, MS and elemental analysis. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Development of protein-cage-based delivery nanoplatforms by polyvalently displaying β-cyclodextrins on the surface of ferritins through copper(I)-catalyzed azide/alkyne cycloaddition.

    Science.gov (United States)

    Kwon, Chanho; Kang, Young Ji; Jeon, Sangbin; Jung, Seunho; Hong, Sung You; Kang, Sebyung

    2012-11-01

    Protein cages are spherical hollow macromolecules that are attractive platforms for the construction of nanoscale cargo delivery vehicles. Human heavy-chain ferritin (HHFn) is modified genetically to control the number and position of functional groups per cage. 24 β-CDs are conjugated precisely to the modified HHFn in specific locations through thiol-maleimide Michael-type addition followed by copper(I)-catalyzed azide/alkyne cycloaddition (CuAAC). The resulting human ferritins displaying β-CDs (β-CD-C90 HHFn) can form inclusion complexes with FITC-AD, which can slowly release the guest molecule reversibly in a buffer solution via non-covalent β-CD/AD interactions. β-CD-C90 HHFn can potentially be used as delivery vehicles for insoluble drugs. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Cyclic Multiblock Copolymers via Combination of Iterative Cu(0)-Mediated Radical Polymerization and Cu(I)-Catalyzed Azide-Alkyne Cycloaddition Reaction.

    Science.gov (United States)

    Xiao, Lifen; Zhu, Wen; Chen, Jiqiang; Zhang, Ke

    2017-02-01

    Cyclic multiblock polymers with high-order blocks are synthesized via the combination of single-electron transfer living radical polymerization (SET-LRP) and copper-catalyzed azide-alkyne cycloaddition (CuAAC). The linear α,ω-telechelic multiblock copolymer is prepared via SET-LRP by sequential addition of different monomers. The SET-LRP approach allows well control of the block length and sequence as A-B-C-D-E, etc. The CuAAC is then performed to intramolecularly couple the azide and alkyne end groups of the linear copolymer and produce the corresponding cyclic copolymer. The block sequence and the cyclic topology of the resultant cyclic copolymer are confirmed by the characterization of (1) H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Tailoring the hydrophilic/lipophilic balance of clickable mesoporous organosilicas by the copper-catalyzed azide-alkyne cycloaddition click-functionalization.

    Science.gov (United States)

    Noureddine, Achraf; Trens, Philippe; Toquer, Guillaume; Cattoën, Xavier; Man, Michel Wong Chi

    2014-10-21

    We have designed and synthesized a clickable bridged silsesquioxane material featuring pendant alkyne chains as an aggregate of golf-ball-like nanoparticles, as evidenced by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and small- and wide-angle X-ray scattering (SWAXS). Using the copper-catalyzed azide-alkyne cycloaddition reaction with a range of organic azides of variable characteristics, we transformed this parent bridged silsesquioxane into new materials with tunable hydrophilic/lipophilic balance in high conversions while preserving the original morphology. N2, cyclohexane, and water sorption experiments were used to quantify the affinity of these materials toward the sorbates through the determination of their Henry's constants. This resulted in the following hydrophilic scale: M-OH > M-PEG > M-C6 > M-Ph > M-F > M-C16, which was mostly confirmed by SWAXS measurements.

  5. Copper-catalyzed azide-alkyne cycloaddition in the synthesis of polydiacetylene: "click glycoliposome" as biosensors for the specific detection of lectins.

    Science.gov (United States)

    Leal, Manuel Pernía; Assali, Mohyeddin; Fernández, Inmaculada; Khiar, Noureddine

    2011-02-07

    Supramolecular self-assembly of conjugated diacetylenic amphiphile-tethered ligands photopolymerize to afford polydiacetylene (PDA) functional liposomes. Upon specific interaction with a variety of biological analytes in aqueous solution, PDA exhibits rapid colorimetric transitions. The PDA nanoassemblies, which are excellent membrane mimics, include an ene-yne polymeric reporter responsible for the chromatic transitions and the molecular recognition elements that are responsible for selective and specific binding to the biological target. A bottleneck in the fabrication of these colorimetric biosensors is the preparation of the diacetylenic monomer embedded with the recognition element of choice. In the present work, we make use of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as key step in the preparation of sugar-coated liposome biosensors. The regioselective click ligation of the triacetylenic N-(2-propynyl)pentacosa-10,12-diynamide (NPPCDAM) with a variety of mannose- and lactose-tethered azides afforded chemo- and regioselectively the corresponding 1,2,3-triazole. The obtained diacetylenic monomers were incorporated efficiently into vesicles to afford functional mannose- and lactose-coated glycoliposomes. The obtained PDA-based click glycoliposomes have been characterized by using transmission electronic microscopy (TEM), dynamic light scattering (DLS), and UV/Vis spectroscopy. The efficiency of the reported approach was demonstrated by the rapid optimization of the hydrophilic spacer between the lipidic matrix and the mannose head group for the colorimetric detection of Concavalin A. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Novel colorimetric molecular switch based on copper(I)-catalyzed azide-alkyne cycloaddition reaction and its application for flumioxazin detection.

    Science.gov (United States)

    Xie, Lidan; Zheng, Hanye; Ye, Wenmei; Qiu, Suyan; Lin, Zhenyu; Guo, Longhua; Qiu, Bin; Chen, Guonan

    2013-01-21

    A novel colorimetric switch based on the copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has been developed. G-quadruplex-hemin DNAzyme catalyzes the oxidation of 2,2'-azinobis(3-ethylbenzothiozoline)-6-sulfonic acid (ABTS) to form ABTS˙(+), the UV absorbance of the solution increased greatly and the color of the solution changed to dark green. However, in the presence of an azide complex, the absorbance signal decreased and the solution became light green since the catalytic ability of the hemin was inhibited by the azide groups. However, once propargylamine has been added into the above reaction system, which would react with azide groups through the CuAAC reaction, the solution becomes dark green again and the absorption intensity of the system is also increased. The proposed switch allows a good reversibility and can be identified clearly by the naked eye. In addition, the method has been applied to detect some pesticides, which have alkynyl groups (flumioxazin), with high sensitivity and selectivity, where the UV absorbance has a direct linear relationship with the logarithm of flumioxazin concentrations in the range of 0.14-14 nM, and the limit of detection was 0.056 nM (S/N = 3), which can meet the requirement of the maximum residue limits (MRLs) of United States of America (56 nM).

  7. Citrus Peel Additives for One-Pot Triazole Formation by Decarboxylation, Nucleophilic Substitution, and Azide-Alkyne Cycloaddition Reactions

    Science.gov (United States)

    Mendes, Desiree E.; Schoffstall, Allen M.

    2011-01-01

    This undergraduate organic laboratory experiment consists of three different reactions occurring in the same flask: a cycloaddition reaction, preceded by decarboxylation and nucleophilic substitution reactions. The decarboxylation and cycloaddition reactions occur using identical Cu(I) catalyst and conditions. Orange, lemon, and other citrus fruit…

  8. Kinetics and mechanics of photo-polymerized triazole-containing thermosetting composites via the copper(I)-catalyzed azide-alkyne cycloaddition.

    Science.gov (United States)

    Song, Han Byul; Wang, Xiance; Patton, James R; Stansbury, Jeffrey W; Bowman, Christopher N

    2017-06-01

    Several features necessary for polymer composite materials in practical applications such as dental restorative materials were investigated in photo-curable CuAAC (copper(I)-catalyzed azide-alkyne cycloaddition) thermosetting resin-based composites with varying filler loadings and compared to a conventional BisGMA/TEGDMA based composite. Tri-functional alkyne and di-functional azide monomers were synthesized for CuAAC resins and incorporated with alkyne-functionalized glass microfillers for CuAAC composites. Polymerization kinetics, in situ temperature change, and shrinkage stress were monitored simultaneously with a tensometer coupled with FTIR spectroscopy and a data-logging thermocouple. The glass transition temperature was analyzed by dynamic mechanical analysis. Flexural modulus/strength and flexural toughness were characterized in three-point bending on a universal testing machine. The photo-CuAAC polymerization of composites containing between 0 and 60wt% microfiller achieved ∼99% conversion with a dramatic reduction in the maximum heat of reaction (∼20°C decrease) for the 60wt% filled CuAAC composites as compared with the unfilled CuAAC resin. CuAAC composites with 60wt% microfiller generated more than twice lower shrinkage stress of 0.43±0.01MPa, equivalent flexural modulus of 6.1±0.7GPa, equivalent flexural strength of 107±9MPa, and more than 10 times higher energy absorption of 10±1MJm(-3) when strained to 11% relative to BisGMA-based composites at equivalent filler loadings. Mechanically robust and highly tough, photo-polymerized CuAAC composites with reduced shrinkage stress and a modest reaction exotherm were generated and resulted in essentially complete conversion. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  9. Site-specific bioconjugation of a murine dihydrofolate reductase enzyme by copper(I-catalyzed azide-alkyne cycloaddition with retained activity.

    Directory of Open Access Journals (Sweden)

    Sung In Lim

    Full Text Available Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC is an efficient reaction linking an azido and an alkynyl group in the presence of copper catalyst. Incorporation of a non-natural amino acid (NAA containing either an azido or an alkynyl group into a protein allows site-specific bioconjugation in mild conditions via CuAAC. Despite its great potential, bioconjugation of an enzyme has been hampered by several issues including low yield, poor solubility of a ligand, and protein structural/functional perturbation by CuAAC components. In the present study, we incorporated an alkyne-bearing NAA into an enzyme, murine dihydrofolate reductase (mDHFR, in high cell density cultivation of Escherichia coli, and performed CuAAC conjugation with fluorescent azide dyes to evaluate enzyme compatibility of various CuAAC conditions comprising combination of commercially available Cu(I-chelating ligands and reductants. The condensed culture improves the protein yield 19-fold based on the same amount of non-natural amino acid, and the enzyme incubation under the optimized reaction condition did not lead to any activity loss but allowed a fast and high-yield bioconjugation. Using the established conditions, a biotin-azide spacer was efficiently conjugated to mDHFR with retained activity leading to the site-specific immobilization of the biotin-conjugated mDHFR on a streptavidin-coated plate. These results demonstrate that the combination of reactive non-natural amino acid incorporation and the optimized CuAAC can be used to bioconjugate enzymes with retained enzymatic activity.

  10. Site-specific bioconjugation of a murine dihydrofolate reductase enzyme by copper(I)-catalyzed azide-alkyne cycloaddition with retained activity.

    Science.gov (United States)

    Lim, Sung In; Mizuta, Yukina; Takasu, Akinori; Kim, Yong Hwan; Kwon, Inchan

    2014-01-01

    Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is an efficient reaction linking an azido and an alkynyl group in the presence of copper catalyst. Incorporation of a non-natural amino acid (NAA) containing either an azido or an alkynyl group into a protein allows site-specific bioconjugation in mild conditions via CuAAC. Despite its great potential, bioconjugation of an enzyme has been hampered by several issues including low yield, poor solubility of a ligand, and protein structural/functional perturbation by CuAAC components. In the present study, we incorporated an alkyne-bearing NAA into an enzyme, murine dihydrofolate reductase (mDHFR), in high cell density cultivation of Escherichia coli, and performed CuAAC conjugation with fluorescent azide dyes to evaluate enzyme compatibility of various CuAAC conditions comprising combination of commercially available Cu(I)-chelating ligands and reductants. The condensed culture improves the protein yield 19-fold based on the same amount of non-natural amino acid, and the enzyme incubation under the optimized reaction condition did not lead to any activity loss but allowed a fast and high-yield bioconjugation. Using the established conditions, a biotin-azide spacer was efficiently conjugated to mDHFR with retained activity leading to the site-specific immobilization of the biotin-conjugated mDHFR on a streptavidin-coated plate. These results demonstrate that the combination of reactive non-natural amino acid incorporation and the optimized CuAAC can be used to bioconjugate enzymes with retained enzymatic activity.

  11. Development of copper-catalyzed azide-alkyne cycloaddition for increased in vivo efficacy of interferon β-1b by site-specific PEGylation.

    Science.gov (United States)

    Nairn, Natalie W; Shanebeck, Kurt D; Wang, Aijun; Graddis, Thomas J; VanBrunt, Michael Pete; Thornton, Kenneth C; Grabstein, Kenneth

    2012-10-17

    The development of protein conjugate therapeutics requires control over the site of modification to allow for reproducible generation of a product with the desired potency, pharmacokinetic, and safety profile. Placement of a single nonnatural amino acid at the desired modification site of a recombinant protein, followed by a bioorthogonal reaction, can provide complete control. To this end, we describe the development of copper-catalyzed azide-alkyne cycloaddition (CuAAC, a click chemistry reaction) for site-specific PEGylation of interferon β-1b (IFNb) containing azidohomoalanine (Aha) at the N-terminus. Reaction conditions were optimized using various propargyl-activated PEGs, tris(benzyltriazolylmethyl)amine (TBTA), copper sulfate, and dithiothreitol (DTT) in the presence of SDS. The requirement for air in order to advance the redox potential of the reaction was investigated. The addition of unreactive PEG diol reduced the required molar ratio to 2:1 PEG-alkyne to IFNb. The resultant method produced high conversion of Aha-containing IFNb to the single desired product. PEG-IFNbs with 10, 20, 30, and 40 kDa linear or 40 kDa branched PEGs were produced with these methods and compared. Increasing PEG size yielded decreasing in vitro antiviral activities along with concomitant increases in elimination half-life, AUC, and bioavailability when administered in rats or monkeys. A Daudi tumor xenograft model provided comparative evaluation of these combined effects, wherein a 40 kDa branched PEG-IFNb was much more effective than conjugates with smaller PEGs or unPEGylated IFNb at preventing tumor growth in spite of dosing with fewer units and lesser frequency. The results demonstrate the capability of site-specific nonnatural amino acid incorporation to generate novel biomolecule conjugates with increased in vivo efficacy.

  12. Structural analysis of porphyrin multilayer films on ITO assembled using copper(I)-catalyzed azide-alkyne cycloaddition by ATR IR.

    Science.gov (United States)

    Palomaki, Peter K B; Dinolfo, Peter H

    2011-12-01

    We report the use of grazing-angle attenuated total reflectance (GATR) IR and polarized UV-vis to determine the molecular structure of porphyrin based molecular multilayer films grown in a layer-by-layer (LbL) fashion using copper-catalyzed azide-alkyne cycloaddition (CuAAC). The molecular orientation and bonding motif present in multilayer films of this type could impact their photophysical and electrochemical properties as well as potential applications. Multilayer films of M(II) 5,10,15,20-tetra(4-ethynylphenyl)porphyrin (1 M = Zn, 2 M = Cu) and azido based linkers 3-5 were used to fabricate the films on ITO substrates. Electrochemically determined coverage of films containing 2 match the trends observed in the absorbance. GATR-IR spectral analysis of the films indicate that CuAAC reactivity is leading to 1,4-triazole linked multilayers with increasing porphyrin and linker IR characteristic peaks. Films grown using all azido-linkers (3-5) display an oscillating trend in azide IR intensity suggesting that the surface bound azido group reacts with 1 and that further layering can occur through additional reaction with linkers, regenerating the azide surface. Films containing linker 5 in particular show an overall increase in azide content suggesting that only two of the three available groups react during multilayer fabrication, causing an overall buildup of azide content in the film. Films of 1 with linker 3 and 5 showed an average porphyrin plane angle of 46.4° with respect to the substrate as determined by GATR FT-IR. Polarized UV-vis absorbance measurements correlate well with the growth angle calculated by IR. The orientation of the porphyrin plane within the multilayer structures suggests that the CuAAC-LbL process results in a film with a trans bonding motif. © 2011 American Chemical Society

  13. Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC).

    Science.gov (United States)

    Mandoli, Alessandro

    2016-09-05

    The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC) have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.

  14. Recent Advances in Recoverable Systems for the Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction (CuAAC

    Directory of Open Access Journals (Sweden)

    Alessandro Mandoli

    2016-09-01

    Full Text Available The explosively-growing applications of the Cu-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between organic azides and alkynes (CuAAC have stimulated an impressive number of reports, in the last years, focusing on recoverable variants of the homogeneous or quasi-homogeneous catalysts. Recent advances in the field are reviewed, with particular emphasis on systems immobilized onto polymeric organic or inorganic supports.

  15. Synthesis of sugar-based silica gels by copper-catalysed azide-alkyne cycloaddition via a single-step azido-activated silica intermediate and the use of the gels in hydrophilic interaction chromatography.

    Science.gov (United States)

    Moni, Lisa; Ciogli, Alessia; D'Acquarica, Ilaria; Dondoni, Alessandro; Gasparrini, Francesco; Marra, Alberto

    2010-05-17

    Novel sugar-based silica gels were prepared by exploiting the copper-catalysed azide-alkyne cycloaddition (CuAAC) of two different sugar alkynes, namely, ethynyl C-galactoside 1 and propargyl O-lactoside 2, with new single-step azido-activated silica gels. The fully characterised stationary phases were generally used for hydrophilic interaction chromatography (HILIC), with particular application in the stereoselective separation of monosaccharides. Dynamic HILIC (DHILIC) experiments were performed to evaluate the influence of mutarotation on the chromatographic peak shapes of two interconverting sugar anomers. The potential of such materials was shown in the separation of other highly polar compounds, including amino acids and flavonoids.

  16. Theoretical studies on the regioselectivity of iridium-catalyzed 1,3-dipolar azide-alkyne cycloaddition reactions.

    Science.gov (United States)

    Luo, Qiong; Jia, Guochen; Sun, Jianwei; Lin, Zhenyang

    2014-12-19

    Iridium-catalyzed cycloaddition of thioalkynes and bromoalkynes with azides have been investigated with the aid of density functional theory (DFT) calculations at the M06 level of theory. Our investigation focused on the different regioselectivity observed for the reactions of the two classes of alkynes. The DFT results have shown that the mechanisms of cycloaddition reactions using thioalkynes and bromoalkynes as substrates are similar yet different. The reactions of thioalkynes occur via a metallabicyclic Ir-carbene intermediate formed through alkyne-azide oxidative coupling via attack of the azide terminal nitrogen toward the β alkyne carbon, whose carbene ligand is stabilized by an alkylthio/arylthio substituent. Reductive elimination from the intermediate leads to the formation of the experimentally observed 5-sulfenyltriazole. In the reactions of bromoalkynes RC≡CBr, the reaction mechanism involves the initial formation of a six-membered-ring metallacycle intermediate in the oxidative coupling step. The six-membered-ring intermediate then undergoes isomerization via migrating the terminal azide nitrogen from the β carbon to the α carbon to form a much less stable metallabicyclic Ir-carbene species from which reductive elimination gives 4-bromotriazole.

  17. Silver-catalysed azide-alkyne cycloaddition (AgAAC): assessing the mechanism by density functional theory calculations

    Science.gov (United States)

    Banerji, Biswadip; Chandrasekhar, K.; Killi, Sunil Kumar; Pramanik, Sumit Kumar; Uttam, Pal; Sen, Sudeshna; Maiti, Nakul Chandra

    2016-09-01

    `Click reactions' are the copper catalysed dipolar cycloaddition reaction of azides and alkynes to incorporate nitrogens into a cyclic hydrocarbon scaffold forming a triazole ring. Owing to its efficiency and versatility, this reaction and the products, triazole-containing heterocycles, have immense importance in medicinal chemistry. Copper is the only known catalyst to carry out this reaction, the mechanism of which remains unclear. We report here that the `click reactions' can also be catalysed by silver halides in non-aqueous medium. It constitutes an alternative to the well-known CuAAC click reaction. The yield of the reaction varies on the type of counter ion present in the silver salt. This reaction exhibits significant features, such as high regioselectivity, mild reaction conditions, easy availability of substrates and reasonably good yields. In this communication, the findings of a new catalyst along with the effect of solvent and counter ions will help to decipher the still obscure mechanism of this important reaction.

  18. Layer-by-Layer Fabrication of Porphyrin Multilayer Films via Copper(I)-Catalyzed Azide-Alkyne Cycloaddition: Film Properties and Applications in Dye-Sensitized Solar Cells

    Science.gov (United States)

    Palomaki, Peter Karl Bunk

    Solar energy may be the only renewable source of energy available to the human race that could provide the energy we require while at the same time minimizing negative impacts on the planet and population. These characteristics may be instrumental in diminishing the potential for societal conflict. In order for photovoltaic devices to succeed on a global scale, research and development must lead to reduced costs and/or increased efficiency. Dye-Sensitized Solar Cells (DSSCs) are one class of nextgeneration photovoltaic technologies with the potential to realize these goals. Herein, I describe efforts towards developing a new light harvesting array of chromophores assembled on oxide substrates using copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC or ‘click’ chemistry) that could prove useful in improving DSCC performance while maintaining low cost and simple fabrication. Specifically, molecular multilayers of porphyrin-based chromophores have been fabricated via sequential selflimiting CuAAC reactions to generate multilayered light harvesting films. Films of synthetic porphyrins, perylenes, and mixtures of the two are constructed in order to highlight the versatility of this molecular layer-by-layer (LbL) technique. Characterization in the form of electrochemical techniques, UV-Visible spectroscopy, infrared spectroscopy (IR), and water contact angle all indicate that the films are reacting as expected. Film thickness and morphology are investigated using X-ray reflectivity showing that film growth displays a high degree of linearity, while the roughness increases with thickness. Growth angles based on the porphyrin plane are estimated via a comparison of molecular models and experimentally determined thickness measurements. A more finite measurement of growth angle (and as a result the primary bonding mode) is determined by grazing angle IR spectroscopy. Blocking layer studies suggest that the films could be useful as a self-passivating layer in DSSCs to

  19. Porphyrin-Based Molecular Multilayer Films Assembled via Copper(I)-Azide-Alkyne Cycloaddition Coupled Layer-by-Layer Method for Light Harvesting Applications

    Science.gov (United States)

    Krawicz, Alexandra

    We have developed a Layer-by-Layer (LbL) method for the fabrication of thin-film molecular multilayers on electron-beam evaporated Au surfaces. Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) coupling reactions were used for initial surface attachment and subsequent LbL deposition. The molecular multilayer films comprised of porphyrins and multi-azido linkers were assembled and characterized with a multitude of surface techniques. The electrochemical and photophysical properties of the thin-films can be tuned through synthetic modification of the individual building blocks, resulting in new porphyrin multilayers. These films have applications as light-harvesting arrays in Dye-Sensitized Solar Cells (DSSC), molecular electronics, and sensors. Herein, we demonstrate the reproducible growth trends and optical properties of multilayer films on Au surfaces modified with an azido-terminated alkanethiol self-assembled monolayer. Multilayer growth was followed by UV-Vis absorption and specular reflectance spectroscopy. Film thickness and optical constants were obtained through spectroscopic ellipsometry. The resulting extinction coefficients were consistent with typical porphyrin absorption spectra. The multilayers show consistent linear growth in absorbance and film thickness over tens of layers as well as continuity and moderate ordering in their molecular structure. This flexible molecular LbL technique has the potential to control the nanoscale structure and function of the thin films. Topology and local surface roughness were examined by TM-AFM, and elemental composition found by X-ray Photoelectron Spectroscopy (XPS) was consistent with the expected morphology of the porphyrin based films assembled on Au surfaces. Additionally, the copper content of the resulting films was quantified by XPS, and the utility of ethylenediaminetetraacetic acid disodium salt (Na2EDTA) was examined to remove the adventitious Cu catalyst. The gold supported multilayers were

  20. Bioorthogonal phase-directed copper-catalyzed azide-alkyne cycloaddition (PDCuAAC) coupling of selectively cross-linked superoxide dismutase dimers produces a fully active bis-dimer.

    Science.gov (United States)

    Siren, Erika M J; Singh, Serena; Kluger, Ronald

    2015-10-28

    Superoxide dismutase (SOD) is a 32 kDa dimeric enzyme that actively removes a toxic oxygen species within red cells. The acellular protein itself does not survive circulation as it is filtered through the kidney. Conjugating the protein to another SOD should increase the size of the dual protein above the threshold for filtration by the kidney, making the material a potential therapeutic in circulation. Site-selective chemical cross-linking of SOD introduces a bioorthogonal azide group on the cross-link so that two SODs react efficiently with a bis-alkyne through phase-directed copper-catalyzed azide-alkyne cycloaddition (PDCuAAC). The modification has a negligible effect on the catalytic activity of the constituent proteins. Consistent with the retained activity, circular dichroism (CD) spectroscopy indicates that the secondary structures of the proteins are similar to that of the native protein.

  1. Utilizing copper(I) catalyzed azide-alkyne Huisgen 1,3-dipolar cycloaddition for the surface modification of colloidal particles with electroactive and emissive moieties

    Science.gov (United States)

    Rungta, Parul

    " chemistry; Aqueous-phase 83 nm poly(propargyl acrylate) (PA) nanoparticles were surface-functionalized with sparingly water soluble fluorescent moieties through a copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) (i.e., "click" transformation) to produce fluoroprobes with a large Stokes shift. For moieties which could not achieve extensive surface coverage on the particles utilizing a standard click transformation procedure, the presence of beta-cyclodextrin (beta-CD) during the transformation enhanced the grafting density onto the particles. For an oxadiazole containing molecule (AO), an azide-modified coumarin 6 (AD1) and a polyethylene glycol modified naphthalimide-based emitter (AD2), respectively, an 84%, 17% and 5% increase in the grafting densities were observed, when the transformation was performed in the presence of beta-CD. In contrast, a carbazolyl-containing moiety (AC) exhibited a slight retardation in the final grafting density when beta-CD was employed. Photoluminescence studies indicated that AC & AO when attached to the particles form an exciplex. An efficient energy transfer from the exciplex to the surface attached AD2 resulted in a total Stokes shift of 180 nm for the modified particles. (3) The synthesis and characterization of near-infrared (NIR) emitting particles for potential applications in cancer therapy. PA particles were surface modified through the "click" transformation of an azide-terminated indocyanine green (azICG), an NIR emitter, and poly(ethylene glycol) (azPEG) chains of various molecular weights. The placement of azICG onto the surface of the particles allowed for the chromophores to complex with bovine serum albumin (BSA) when dispersed in PBS that resulted in an enhancement of the dye emission. In addition, the inclusion of azPEG with the chromophores onto the particle surface resulted in a synergistic nine-fold enhancement of the fluorescence intensity, with azPEGs of increasing molecular weight amplifying the response

  2. Preparation of 18F-labeled peptides using the copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition.

    Science.gov (United States)

    Gill, Herman S; Marik, Jan

    2011-10-13

    An optimized procedure for preparing fluorine-18 ((18)F)-labeled peptides by the copper-catalyzed azide-alkyne 1,3-dipolar cyloaddition (CuAAC) is presented here. The two-step radiosynthesis begins with the microwave-assisted nucleophilic (18)F-fluorination of a precursor containing a terminal p-toluenesulfonyl, terminal azide and polyethylene glycol backbone. The resulting (18)F-fluorinated azide-containing building block is coupled to an alkyne-decorated peptide by the CuAAC. The reaction is accelerated by the copper(I)-stabilizing ligand bathophenanthroline disulfonate and can be performed in either reducing or nonreducing conditions (e.g., to preserve disulfide bonds). After an HPLC purification, (18)F-labeled peptide can be obtained with a 31 ± 6% radiochemical yield (n = 4, decay-corrected from (18)F-fluoride elution) and a specific activity of 39.0 ± 12.4 Ci μmol(-1) within 77 ± 4 min.

  3. A signal-on electrochemical DNA biosensor based on potential-assisted Cu(I)-catalyzed azide-alkyne cycloaddition mediated labeling of hairpin-like oligonucleotide with electroactive probe.

    Science.gov (United States)

    Hu, Qiong; Kong, Jinming; Li, Yajie; Zhang, Xueji

    2016-01-15

    A novel electrochemical biosensor was developed for the signal-on detection of sequence-specific DNA by exploiting potential-assisted Cu(I)-catalyzed azide-alkyne cycloaddition (φCuAAC) as an efficient approach for the labeling of hairpin-like oligonucleotide (hairpin) with electroactive probe. The hairpins, dually labeled with thiol and azide at either terminal, were firstly self-assembled on gold electrode and served as the capture probes for the specific recognition of target DNA. Upon hybridization with target DNA, the surface-confined hairpins were unfolded, liberating the azide-containing terminals away from electrode surface. Subsequently, the unfolded hairpins were conveniently and efficiently labeled with ethynylferrocene (EFC) via the φCuAAC. The quantitatively labeled EFC was finally measured via differential pulse voltammetry (DPV) for the signal-on electrochemical detection of sequence-specific DNA. The biosensor presented a good linear response over the range from 1pM to 1nM with a detection limit of 0.62pM. Results also revealed that it was highly specific and held a good detection capability in serum samples. Furthermore, the ability to chemoselectively label hairpin-like oligonucleotide with signal reporter by electrical addressing, together with the simplicity and efficiency of the φCuAAC, makes it compatible with microfluidic devices and microelectrode arrays to achieve the miniaturized and multiplexed detections.

  4. Synthesis of ferrocene-labeled steroids via copper-catalyzed azide-alkyne cycloaddition. Reactivity difference between 2β-, 6β- and 16β-azido-androstanes.

    Science.gov (United States)

    Fehér, Klaudia; Balogh, János; Csók, Zsolt; Kégl, Tamás; Kollár, László; Skoda-Földes, Rita

    2012-06-01

    Copper-catalyzed cycloaddition of steroidal azides and ferrocenyl-alkynes were found to be an efficient methodology for the synthesis of ferrocene-labeled steroids. At the same time, a great difference between the reactivity of 2β- or 16β-azido-androstanes and a sterically hindered 6β-azido steroid toward both ferrocenyl-alkynes and simple alkynes, such as phenylacetylene, 1-octyne, propargyl acetate and methyl propiolate, was observed.

  5. Efficient access to new chemical space through flow--construction of druglike macrocycles through copper-surface-catalyzed azide-alkyne cycloaddition reactions.

    Science.gov (United States)

    Bogdan, Andrew R; James, Keith

    2010-12-27

    A series of 12- to 22-membered macrocycles, with druglike functionality and properties, have been generated by using a simple and efficient copper-catalyzed azide-acetylene cycloaddition reaction, conducted in flow in high-temperature copper tubing, under environmentally friendly conditions. The triazole-containing macrocycles have been generated in up to 90 % yield in a 5 min reaction, without resorting to the high-dilution conditions typical of macrocyclization reactions. This approach represents a very efficient method for constructing this important class of molecules, in terms of yield, concentration, and environmental considerations.

  6. AZIDE-ALKYNE CLICK POLYMERIZATION: AN UPDATE

    Institute of Scientific and Technical Information of China (English)

    Hong-kun Li; Jing-zhi Sun; An-jun Qin; Ben Zhong Tang

    2012-01-01

    The great achievements of click chemistry have encouraged polymer scientists to use this reaction in their field.This review assembles an update of the advances of using azide-alkyne click polymerization to prepare functional polytriazoles (PTAs) with linear and hyperbranched structures.The Cu(Ⅰ)-mediated click polymerization furnishes 1,4-regioregular PTAs,whereas,the metal-free click polymerization of propiolates and azides produces PTAs with 1,4-regioisomer contents up to 90%.The PTAs display advanced functions,such as aggregation-induced emission,thermal stability,biocompatibility and optical nonlinearity.

  7. Biocompatible Azide-Alkyne "Click" Reactions for Surface Decoration of Glyco-Engineered Cells.

    Science.gov (United States)

    Gutmann, Marcus; Memmel, Elisabeth; Braun, Alexandra C; Seibel, Jürgen; Meinel, Lorenz; Lühmann, Tessa

    2016-05-03

    Bio-orthogonal copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been widely used to modify azide- or alkyne-bearing monosaccharides on metabolic glyco-engineered mammalian cells. Here, we present a systematic study to elucidate the design space for the cytotoxic effects of the copper catalyst on NIH 3T3 fibroblasts and on HEK 293-F cells. Monitoring membrane integrity by flow cytometry and RT-PCR analysis with apoptotic and anti-apoptotic markers elucidated the general feasibility of CuAAC, with exposure time of the CuAAC reaction mixture having the major influence on biocompatibility. A high labeling efficiency of HEK 293-F cells with a fluorescent alkyne dye was rapidly achieved by CuAAC in comparison to copper free strain-promoted azide-alkyne cycloaddition (SPAAC). The study details effective and biocompatible conditions for CuAAC-based modification of glyco-engineered cells in comparison to its copper free alternative.

  8. A Theoretical Study of the Relationship between the Electrophilicity ω Index and Hammett Constant σp in [3+2] Cycloaddition Reactions of Aryl Azide/Alkyne Derivatives

    Directory of Open Access Journals (Sweden)

    Hicham Ben El Ayouchia

    2016-10-01

    Full Text Available The relationship between the electrophilicity ω index and the Hammett constant σp has been studied for the [2+3] cycloaddition reactions of a series of para-substituted phenyl azides towards para-substituted phenyl alkynes. The electrophilicity ω index—a reactivity density functional theory (DFT descriptor evaluated at the ground state of the molecules—shows a good linear relationship with the Hammett substituent constants σp. The theoretical scale of reactivity correctly explains the electrophilic activation/deactivation effects promoted by electron-withdrawing and electron-releasing substituents in both azide and alkyne components.

  9. The use of azide-alkyne click chemistry in recent syntheses and applications of polytriazole-based nanostructured polymers

    Science.gov (United States)

    Shi, Yi; Cao, Xiaosong; Gao, Haifeng

    2016-02-01

    The rapid development of efficient organic click coupling reactions has significantly facilitated the construction of synthetic polymers with sophisticated branched nanostructures. This Feature Article summarizes the recent progress in the application of efficient copper-catalyzed and copper-free azide-alkyne cycloaddition (CuAAC and CuFAAC) reactions in the syntheses of dendrimers, hyperbranched polymers, star polymers, graft polymers, molecular brushes, and cyclic graft polymers. Literature reports on the interesting properties and functions of these polytriazole-based nanostructured polymers are also discussed to illustrate their potential applications as self-healing polymers, adhesives, polymer catalysts, opto-electronic polymer materials and polymer carriers for drug and imaging molecules.

  10. Tethering antimicrobial peptides onto chitosan: Optimization of azide-alkyne "click" reaction conditions.

    Science.gov (United States)

    Barbosa, Mariana; Vale, Nuno; Costa, Fabíola M T A; Martins, M Cristina L; Gomes, Paula

    2017-06-01

    Antimicrobial peptides (AMP) are promising alternatives to classical antibiotics, due to their high specificity and potency at low concentrations, and low propensity to elicit pathogen resistance. Immobilization of AMP onto biomaterials is an emergent field of research, towards creation of novel antimicrobial materials able to avoid formation of biofilms on the surfaces of medical devices. Herein, we report the chemical route towards one such material, where chitosan was used as biocompatible carrier for the covalent grafting of Dhvar-5, a well-known potent AMP, via the chemoselective ("click") Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The material's structure, as well as peptide loading, were confirmed by Fourier-transformed infra-red (FT-IR) and X-ray photoelectron (XPS) spectroscopies, and by Amino Acid Analysis (AAA), respectively. Results herein reported demonstrate that, with proper optimization, the "click" CuAAC is an attractive approach for the tethering of AMP onto chitosan, in order to create novel antimicrobial materials potentially valuable for biomedical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Acid-base jointly promoted copper(I)-catalyzed azide-alkyne cycloaddition.

    Science.gov (United States)

    Shao, Changwei; Wang, Xinyan; Zhang, Qun; Luo, Sheng; Zhao, Jichen; Hu, Yuefei

    2011-08-19

    In this novel acid-base jointly promoted CuAAC, the combination of CuI/DIPEA/HOAc was developed as a highly efficient catalytic system. The functions of DIPEA and HOAc have been assigned, and HOAc was recognized to accelerate the conversions of the C-Cu bond-containing intermediates and buffer the basicity of DIPEA. As a result, all drawbacks occurring in the popular catalytic system CuI/NR(3) were overcome easily.

  12. Solvent-free copper-catalyzed azide-alkyne cycloaddition under mechanochemical activation.

    Science.gov (United States)

    Rinaldi, Laura; Martina, Katia; Baricco, Francesca; Rotolo, Laura; Cravotto, Giancarlo

    2015-02-09

    The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC). All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number) have been optimized. This new, efficient, facile and eco-friendly procedure has been tested on a number of different substrates and in all cases afforded the corresponding 1,4-disubstituted 1,2,3-triazole derivatives in high yields and purities. The final compounds were isolated in almost quantitative overall yields after simple filtration, making this procedure facile and rapid. The optimized CuAAC protocol was efficiently applied even with bulky functionalized β-cyclodextrins (β-CD) and scaled-up to 10 g of isolated product.

  13. Solvent-Free Copper-Catalyzed Azide-Alkyne Cycloaddition under Mechanochemical Activation

    Directory of Open Access Journals (Sweden)

    Laura Rinaldi

    2015-02-01

    Full Text Available The ball-mill-based mechanochemical activation of metallic copper powder facilitates solvent-free alkyne-azide click reactions (CuAAC. All parameters that affect reaction rate (i.e., milling time, revolutions/min, size and milling ball number have been optimized. This new, efficient, facile and eco-friendly procedure has been tested on a number of different substrates and in all cases afforded the corresponding 1,4-disubstituted 1,2,3-triazole derivatives in high yields and purities. The final compounds were isolated in almost quantitative overall yields after simple filtration, making this procedure facile and rapid. The optimized CuAAC protocol was efficiently applied even with bulky functionalized β-cyclodextrins (β-CD and scaled-up to 10 g of isolated product.

  14. Well-defined polyethylene-based graft terpolymers by combining nitroxide-mediated radical polymerization, polyhomologation and azide/alkyne “click” chemistry†

    KAUST Repository

    Alkayal, Nazeeha

    2016-03-30

    Novel well–defined polyethylene–based graft terpolymers were synthesized via the “grafting onto” strategy by combining nitroxide-mediated radical polymerization (NMP), polyhomologation and copper (I)-catalyzed azide-alkyne cycloaddition (CuAAC) “click” chemistry. Three steps were involved in this approach: (i) synthesis of alkyne-terminated polyethylene-b-poly(ε-caprolactone) (PE-b-PCL-alkyne) block copolymers (branches) by esterification of PE-b-PCL-OH with 4-pentynoic acid; the PE-b-PCL-OH was obtained by polyhomologation of dimethylsulfoxonium methylide to afford PE-OH, followed by ring opening polymerization of ε-caprolactone using the PE-OH as macroinitiator, (ii) synthesis of random copolymers of styrene (St) and 4-chloromethylstyrene (4-CMS) with various CMS contents, by nitroxide-mediated radical copolymerization (NMP), and conversion of chloride to azide groups by reaction with sodium azide (NaN3) (backbone) and (iii) “click” linking reaction to afford the PE-based graft terpolymers. All intermediates and final products were characterized by high-temperature size exclusion chromatography (HT-SEC), Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance spectroscopy (1H NMR) and differential scanning calorimetry (DSC).

  15. Quick and highly efficient copper-catalyzed cycloaddition of organic azides with terminal alkynes.

    Science.gov (United States)

    Wang, Dong; Zhao, Mingming; Liu, Xiang; Chen, Yongxin; Li, Na; Chen, Baohua

    2012-01-14

    Good to excellent yields of 1,4-disubstituted 1,2,3-triazoles were obtained within 2-25 min when the Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction was carried out under solvent-free conditions, with [Cu(phen)(PPh(3))(2)]NO(3) (1mol%) as the catalyst.

  16. Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles.

    Science.gov (United States)

    Sarwar, Atif; Katas, Haliza; Samsudin, Siti Noradila; Zin, Noraziah Mohamad

    2015-01-01

    Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP) and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC) of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene) triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide) triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68) demonstrated the safety; suggesting that these derivatives could be used in future

  17. Regioselective Sequential Modification of Chitosan via Azide-Alkyne Click Reaction: Synthesis, Characterization, and Antimicrobial Activity of Chitosan Derivatives and Nanoparticles.

    Directory of Open Access Journals (Sweden)

    Atif Sarwar

    Full Text Available Recently, the attention of researchers has been drawn toward the synthesis of chitosan derivatives and their nanoparticles with enhanced antimicrobial activities. In this study, chitosan derivatives with different azides and alkyne groups were synthesized using click chemistry, and these were further transformed into nanoparticles by using the ionotropic gelation method. A series of chitosan derivatives was successfully synthesized by regioselective modification of chitosan via an azide-alkyne click reaction. The amino moieties of chitosan were protected during derivatization by pthaloylation and subsequently unblocked at the end to restore their functionality. Nanoparticles of synthesized derivatives were fabricated by ionic gelation to form complexes of polyanionic penta-sodium tripolyphosphate (TPP and cationic chitosan derivatives. Particle size analysis showed that nanoparticle size ranged from 181.03 ± 12.73 nm to 236.50 ± 14.32 nm and had narrow polydispersity index and positive surface charge. The derivatives and corresponding nanoparticles were evaluated in vitro for antibacterial and antifungal activities against three gram-positive and gram-negative bacteria and three fungal strains, respectively. The minimum inhibitory concentration (MIC of all derivatives ranged from 31.3 to 250 µg/mL for bacteria and 188 to1500 µg/mL for fungi and was lower than that of native chitosan. The nanoparticles with MIC ranging from 1.56 to 25 µg/mLfor bacteria and 94 to 750 µg/mL for fungi exhibited higher activity than the chitosan derivatives. Chitosan O-(1-methylbenzene triazolyl carbamate and chitosan O-(1-methyl phenyl sulfide triazolyl carbamate were the most active against the tested bacterial and fungal strains. The hemolytic assay on erythrocytes and cell viability test on two different cell lines (Chinese hamster lung fibroblast cells V79 and Human hepatic cell line WRL68 demonstrated the safety; suggesting that these derivatives could be

  18. Ribosome-Templated Azide-Alkyne Cycloadditions: Synthesis of Potent Macrolide Antibiotics by In Situ Click Chemistry.

    Science.gov (United States)

    Glassford, Ian; Teijaro, Christiana N; Daher, Samer S; Weil, Amy; Small, Meagan C; Redhu, Shiv K; Colussi, Dennis J; Jacobson, Marlene A; Childers, Wayne E; Buttaro, Bettina; Nicholson, Allen W; MacKerell, Alexander D; Cooperman, Barry S; Andrade, Rodrigo B

    2016-03-09

    Over half of all antibiotics target the bacterial ribosome-nature's complex, 2.5 MDa nanomachine responsible for decoding mRNA and synthesizing proteins. Macrolide antibiotics, exemplified by erythromycin, bind the 50S subunit with nM affinity and inhibit protein synthesis by blocking the passage of nascent oligopeptides. Solithromycin (1), a third-generation semisynthetic macrolide discovered by combinatorial copper-catalyzed click chemistry, was synthesized in situ by incubating either E. coli 70S ribosomes or 50S subunits with macrolide-functionalized azide 2 and 3-ethynylaniline (3) precursors. The ribosome-templated in situ click method was expanded from a binary reaction (i.e., one azide and one alkyne) to a six-component reaction (i.e., azide 2 and five alkynes) and ultimately to a 16-component reaction (i.e., azide 2 and 15 alkynes). The extent of triazole formation correlated with ribosome affinity for the anti (1,4)-regioisomers as revealed by measured Kd values. Computational analysis using the site-identification by ligand competitive saturation (SILCS) approach indicated that the relative affinity of the ligands was associated with the alteration of macrolactone+desosamine-ribosome interactions caused by the different alkynes. Protein synthesis inhibition experiments confirmed the mechanism of action. Evaluation of the minimal inhibitory concentrations (MIC) quantified the potency of the in situ click products and demonstrated the efficacy of this method in the triaging and prioritization of potent antibiotics that target the bacterial ribosome. Cell viability assays in human fibroblasts confirmed 2 and four analogues with therapeutic indices for bactericidal activity over in vitro mammalian cytotoxicity as essentially identical to solithromycin (1).

  19. One pot 'click' reactions : tandem enantioselective biocatalytic epoxide ring opening and [3+2] azide alkyne cycloaddition

    NARCIS (Netherlands)

    Campbell-Verduyn, Lachlan S.; Szymanski, Wiktor; Postema, Christiaan P.; Dierckx, Rudi A.; Elsinga, Philip H.; Janssen, Dick B.; Feringa, Ben L.

    2010-01-01

    Halohydrin dehalogenase (HheC) can perform enantioselective azidolysis of aromatic epoxides to 1,2-azido alcohols which are subsequently ligated to alkynes producing chiral hydroxy triazoles in a one-pot procedure with excellent enantiomeric excess.

  20. Well-Defined Diimine Copper(I Complexes as Catalysts in Click Azide-Alkyne Cycloaddition Reactions

    Directory of Open Access Journals (Sweden)

    Silvia Díez-González

    2013-07-01

    Full Text Available A series of 1,4-disubstituted 1,2,3-triazoles have been prepared in high yields while respecting the stringent Click criteria. In these reactions, highly stable pre-formed complexes bearing diimine ligands were used.

  1. Well-defined diimine copper(I) complexes as catalysts in click azide-alkyne cycloaddition reactions.

    Science.gov (United States)

    Barta, Jordi Markalain; Díez-González, Silvia

    2013-07-26

    A series of 1,4-disubstituted 1,2,3-triazoles have been prepared in high yields while respecting the stringent Click criteria. In these reactions, highly stable pre-formed complexes bearing diimine ligands were used.

  2. Continuous metal scavenging and coupling to one-pot copper-catalyzed azide-alkyne cycloaddition click reaction in flow

    NARCIS (Netherlands)

    Vural - Gursel, Dr. Iris; Aldiansyah, Ferry; Wang, Qi; Noël, Timothy; Hessel, Volker

    2015-01-01

    Increasing usage of catalytic chemistry calls for efficient removal of metal traces. This paper describes the development and optimization of a scavenger-based extraction in flow to remove metal catalysts. It enables liquid-liquid extraction with slug flow and phase separation with a porous fluoropo

  3. Continuous metal scavenging and coupling to one-pot copper-catalyzed azide-alkyne cycloaddition click reaction in flow

    NARCIS (Netherlands)

    Vural - Gursel, Dr. Iris; Aldiansyah, Ferry; Wang, Qi; Noël, Timothy; Hessel, Volker

    2015-01-01

    Increasing usage of catalytic chemistry calls for efficient removal of metal traces. This paper describes the development and optimization of a scavenger-based extraction in flow to remove metal catalysts. It enables liquid-liquid extraction with slug flow and phase separation with a porous

  4. Metal Free Azide-Alkyne Click Reaction: Role of Substituents and Heavy Atom Tunneling.

    Science.gov (United States)

    Karmakar, Sharmistha; Datta, Ayan

    2015-09-03

    Metal free click reactions provide an excellent noninvasive tool to modify and understand the processes in biological systems. Release of ring strain in cyclooctynes on reaction with azides on the formation of triazoles results in small activation energies for various intermolecular Huisgen reactions (1-9). Substitution of difluoro groups at the α, α' position of the cyclooctyne ring enhances the rates of cycloadditions by 10 and 20 times for methyl azide and benzyl azide respectively at room temperature. The computed rate enhancement on difluoro substitution using direct dynamical calculations using the canonical variational transition state theory (CVT/CAG) with small curvature tunneling (SCT) corrections are in excellent agreement with the experimental results. For the intramolecular click reaction (10) notwithstanding its much higher activation energy, quantum mechanical tunneling (QMT) enhances the rate of cycloaddition significantly and increases the N(14)/N(15) primary kinetic isotope effect at 298 K. QMT is shown to be rather efficient in 10 due to a thin barrier of ∼2.4 Å. The present study shows that tunneling effects can be significant for intramolecular click reactions.

  5. Evaluation of bicinchoninic acid as a ligand for copper(I)-catalyzed azide-alkyne bioconjugations.

    Science.gov (United States)

    Christen, Erik H; Gübeli, Raphael J; Kaufmann, Beate; Merkel, Lars; Schoenmakers, Ronald; Budisa, Nediljko; Fussenegger, Martin; Weber, Wilfried; Wiltschi, Birgit

    2012-09-07

    The Cu(I)-catalyzed cycloaddition of terminal azides and alkynes (click chemistry) represents a highly specific reaction for the functionalization of biomolecules with chemical moieties such as dyes or polymer matrices. In this study we evaluate the use of bicinchoninic acid (BCA) as a ligand for Cu(I) under physiological reaction conditions. We demonstrate that the BCA-Cu(I)-complex represents an efficient catalyst for the conjugation of fluorophores or biotin to alkyne- or azide-functionalized proteins resulting in increased or at least equal reaction yields compared to commonly used catalysts like Cu(I) in complex with TBTA (tris[(1-benzyl-1H-1,2,3-triazol-4-yl)methyl]amine) or BPAA (bathophenanthroline disulfonic acid). The stabilization of Cu(I) with BCA represents a new strategy for achieving highly efficient bioconjugation reactions under physiological conditions in many application fields.

  6. Environmental Friendly Azide-Alkyne Cycloaddition Reaction of Azides, Alkynes, and Organic Halides or Epoxides in Water: Efficient "Click" Synthesis of 1,2,3-Triazole Derivatives by Cu Catalyst

    Institute of Scientific and Technical Information of China (English)

    刘建明; 刘慕文; 岳园园; 姚美焕; 卓克垒

    2012-01-01

    An efficient click synthesis of 1,2,3-triazole derivatives from benzyl halides or alkyl halides, epoxides, terminal alkynes, and sodium azides in the presence of copper salts and relative benzimidazole salts have been developed. This procedure eliminates the need to handle potentially organic azides, which are generated in situ. A broad spec- trum of substrates can participate in the process effectively to produce the desired products in good yields.

  7. Cu/Pd-Catalyzed, Three-Component Click Reaction of Azide, Alkyne, and Aryl Halide: One-Pot Strategy toward Trisubstituted Triazoles.

    Science.gov (United States)

    Wei, Fang; Li, Haoyu; Song, Chuanling; Ma, Yudao; Zhou, Ling; Tung, Chen-Ho; Xu, Zhenghu

    2015-06-05

    A Cu/Pd-catalyzed, three-component click reaction of azide, alkyne, and aryl halide has been developed. By using this Cu/Pd transmetalation relay catalysis, a variety of 1,4,5-trisubstituted 1,2,3-triazoles were quickly assembled in one step in high yields with complete regioselectivity, just like assembling Lego bricks. Notably, different from the well-established CuAAC click reactions only working on terminal alkynes, this reaction offers an alternative solution for the problem of the click reaction of internal alkynes.

  8. Facile synthesis of linear-dendritic cholesteryl-poly(epsilon-caprolactone)-b-(L-lysine)(G2) by thiol-ene and azide-alkyne "click" reactions

    DEFF Research Database (Denmark)

    Javakhishvili, Irakli; Binder, W.H.; Tanner, S.

    2010-01-01

    The construction of a linear-dendritic block copolymer consisting of terminal cholesteryl moiety, poly(epsilon-caprolactone), and a second generation L-lysine dendron has been accomplished by the combination of copper(I) catalyzed azide-alkyne and UV-triggered thiol-ene "click" reactions. Ring......-opening polymerization of E-caprolactone initiated by 5-hexyn-1-ol and Mitsunobu coupling with 4-pentenoic acid provide hetero-telechelic poly(epsilon-caprolactone) bearing terminal alkyne and alkene groups. It is then employed in the sequential "click" reactions with the azide-functionalized dendritic wedge...

  9. Monitoring Wnt Protein Acylation Using an In Vitro Cyclo-Addition Reaction

    Science.gov (United States)

    Tuladhar, Rubina; Yarravarapu, Nageswari; Lum, Lawrence

    2016-01-01

    We describe here a technique for visualizing the lipidation status of Wnt proteins using azide-alkyne cycloaddition chemistry (click chemistry) and SDS-PAGE. This protocol incorporates in vivo labeling of a Wnt-IgG Fc fusion protein using an alkynylated palmitate probe but departs from a traditional approach by incorporating a secondary cycloaddition reaction performed on single-step purified Wnt protein immobilized on protein A resin. This approach mitigates experimental noise by decreasing the contribution of labeling from other palmitoylated proteins and by providing a robust method for normalizing labeling efficiency based on protein abundance. PMID:27590147

  10. Pin-point chemical modification of RNA with diverse molecules through the functionality transfer reaction and the copper-catalyzed azide-alkyne cycloaddition reaction.

    Science.gov (United States)

    Onizuka, Kazumitsu; Shibata, Atsushi; Taniguchi, Yosuke; Sasaki, Shigeki

    2011-05-07

    The internal modification of RNA has been successfully achieved by the functionality transfer reaction (FTR) and following click chemistry with diverse azide compounds. The benefits of the FTR have been demonstrated by its specificity, rapidity, broad applicability, and procedure simplicity. © The Royal Society of Chemistry 2011

  11. Use of copper(I) catalyzed azide alkyne cycloaddition (CuAAC) for the preparation of conjugated pyrrolo[2,3-a]carbazole Pim kinase inhibitors.

    Science.gov (United States)

    Letribot, Boris; Akué-Gédu, Rufine; Santio, Niina M; El-Ghozzi, Malika; Avignant, Daniel; Cisnetti, Federico; Koskinen, Päivi J; Gautier, Arnaud; Anizon, Fabrice; Moreau, Pascale

    2012-04-01

    We have previously demonstrated that pyrrolo[2,3-a]carbazole-3-carbaldehydes are potent Pim kinase inhibitors with in vitro antiproliferative activities. In the present study, we report the synthesis of new pyrrolocarbazoles substituted at the N-10 position. When their ability to inhibit Pim kinase activities were evaluated in in vitro assays, we observed that this nitrogen atom can be substituted without loss of Pim-1 and Pim-3 inhibitory potencies. Moreover, when we added a fluorescent dansyl group (compound 13), we were able to show that 13 penetrates the plasma membrane and enters the cytoplasm. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  12. 18F-Labeling Using Click Cycloadditions

    Directory of Open Access Journals (Sweden)

    Kathrin Kettenbach

    2014-01-01

    Full Text Available Due to expanding applications of positron emission tomography (PET there is a demand for developing new techniques to introduce fluorine-18 (t1/2=109.8 min. Considering that most novel PET tracers are sensitive biomolecules and that direct introduction of fluorine-18 often needs harsh conditions, the insertion of 18F in those molecules poses an exceeding challenge. Two major challenges during 18F-labeling are a regioselective introduction and a fast and high yielding way under mild conditions. Furthermore, attention has to be paid to functionalities, which are usually present in complex structures of the target molecule. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC and several copper-free click reactions represent such methods for radiolabeling of sensitive molecules under the above-mentioned criteria. This minireview will provide a quick overview about the development of novel 18F-labeled prosthetic groups for click cycloadditions and will summarize recent trends in copper-catalyzed and copper-free click 18F-cycloadditions.

  13. Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry.

    Science.gov (United States)

    Zheng, Zhan-Jiang; Wang, Ding; Xu, Zheng; Xu, Li-Wen

    2015-01-01

    The Cu(I)-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles. Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC) for such transformations. In addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted.

  14. Synthesis of bi- and bis-1,2,3-triazoles by copper-catalyzed Huisgen cycloaddition: A family of valuable products by click chemistry

    Directory of Open Access Journals (Sweden)

    Zhan-Jiang Zheng

    2015-12-01

    Full Text Available The Cu(I-catalyzed azide-alkyne cycloaddition reaction, also known as click chemistry, has become a useful tool for the facile formation of 1,2,3-triazoles. Specifically, the utility of this reaction has been demonstrated by the synthesis of structurally diverse bi- and bis-1,2,3-triazoles. The present review focuses on the synthesis of such bi- and bistriazoles and the importance of using copper-promoted click chemistry (CuAAC for such transformations. In addition, the application of bitriazoles and the related CuAAAC reaction in different fields, including medicinal chemistry, coordination chemistry, biochemistry, and supramolecular chemistry, have been highlighted.

  15. Chiral hybrid inorganic-organic materials: synthesis, characterization, and application in stereoselective organocatalytic cycloadditions.

    Science.gov (United States)

    Puglisi, Alessandra; Benaglia, Maurizio; Annunziata, Rita; Chiroli, Valerio; Porta, Riccardo; Gervasini, Antonella

    2013-11-15

    The synthesis of chiral imidazolidinones on mesoporous silica nanoparticles, exploiting two different anchoring sites and two different linkers, is reported. Catalysts 1-4 were prepared starting from l-phenylalanine or l-tyrosine methyl esters and supporting the imidazolidinone onto silica by grafting protocols or azide-alkyne copper(I)-catalyzed cycloaddition. The four catalysts were fully characterized by solid-state NMR, N2 physisorption, SEM, and TGA in order to provide structural assessments, including an evaluation of surface areas, pore dimensions, and catalyst loading. They were used in organocatalyzed Diels-Alder cycloadditions between cyclopentadiene and different aldehydes, affording results comparable to those obtained with the nonsupported catalyst (up to 91% yield and 92% ee in the model reaction between cyclopentadiene and cinnamic aldehyde). The catalysts were recovered from the reaction mixture by simple filtration or centrifugation. The most active catalyst was recycled two times with some loss of catalytic efficiency and a small erosion of ee.

  16. "Click" Chemistry: Application of Copper Metal in Cu-Catalyzed Azomethine Imine-Alkyne Cycloadditions.

    Science.gov (United States)

    Pušavec Kirar, Eva; Grošelj, Uroš; Mirri, Giorgio; Požgan, Franc; Strle, Gregor; Štefane, Bogdan; Jovanovski, Vasko; Svete, Jurij

    2016-07-15

    A series of 16 copper-catalyzed azomethine imine-alkyne cycloaddition (CuAIAC) reactions between four pyrazolidinone-1-azomethine imines and four terminal ynones gave the corresponding fluorescent cycloadducts as bimane analogues in very high yields. The applicability of CuAIAC was demonstrated by the fluorescent labeling of functionalized polystyrene and by using Cu-C and Cu-Fe as catalysts. Experimental evidence, kinetic measurements, and correlation between a clean catalyst surface and the reaction rate are in agreement with a homotopic catalytic system with catalytic Cu(I)-acetylide formed from Cu(0) by "in situ" oxidation. The availability of azomethine imines, mild reaction conditions, simple workup, and scalability make CuAIAC a viable supplement to the Cu-catalyzed azide-alkyne cycloaddition reaction in "click" chemistry.

  17. Synthesis of the copper chelator TGTA and evaluation of its ability to protect biomolecules from copper induced degradation during copper catalyzed azide-alkyne bioconjugation reactions.

    Science.gov (United States)

    Ekholm, F S; Pynnönen, H; Vilkman, A; Koponen, J; Helin, J; Satomaa, T

    2016-01-21

    One of the most successful bioconjugation strategies to date is the copper(I)-catalyzed cycloaddition reaction (CuAAC), however, the typically applied reaction conditions have been found to degrade sensitive biomolecules. Herein, we present a water soluble copper chelator which can be utilized to protect biomolecules from copper induced degradation.

  18. Electronic effects of ruthenium-catalyzed [3+2]-cycloaddition of alkynes and azides

    KAUST Repository

    Hou, Duenren

    2010-11-01

    A combined experimental and theoretical study of ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) reactions is presented and various electronic analyses were conducted to provide a basis in understanding the observed regioselectivity of the 1,2,3-triazole products. Computational studies using density functional theory (DFT) and atoms in molecules quantum theory (AIM) further yield fresh details on the electronic factors that determine the regioselectivity in the RuAAC. It is found that the formation of 1,2,3-triazole products is irreversible and from the Hammett study, the pathway involving a vinyl cationic intermediate is ruled out. The electronic effect favors the formation of 5-electron-donating-group substituted-1,2,3-trizoles. © 2010 Elsevier Ltd. All rights reserved.

  19. Versatile convergent synthesis of a three peptide loop containing protein mimic of whooping cough pertactin by successive Cu(I)-catalyzed azide alkyne cycloaddition on an orthogonal alkyne functionalized TAC-scaffold

    NARCIS (Netherlands)

    Werkhoven, Paul R; van de Langemheen, Helmus|info:eu-repo/dai/nl/341566667; van der Wal, Steffen|info:eu-repo/dai/nl/314571671; Kruijtzer, John A W|info:eu-repo/dai/nl/15207449X; Liskamp, Rob M J|info:eu-repo/dai/nl/069091315

    2014-01-01

    Synthetic mimics of discontinuous epitopes may have a wide range of potential applications, including synthetic vaccines and inhibition of protein-protein interactions. However, synthetic access to these relatively complex peptide molecular constructs is limited. This paper describes a versatile con

  20. Potent naphthoquinones against antimony-sensitive and -resistant Leishmania parasites: synthesis of novel α- and nor-α-lapachone-based 1,2,3-triazoles by copper-catalyzed azide-alkyne cycloaddition.

    Science.gov (United States)

    Guimarães, Tiago T; Pinto, Maria do Carmo F R; Lanza, Juliane S; Melo, Maria N; do Monte-Neto, Rubens L; de Melo, Isadora M M; Diogo, Emilay B T; Ferreira, Vitor F; Camara, Celso A; Valença, Wagner O; de Oliveira, Ronaldo N; Frézard, Frédéric; da Silva, Eufrânio N

    2013-05-01

    Continuing our screening program for novel anti-parasite compounds, we synthesized seven 1,4-naphthoquinones coupled to 1,2,3-triazoles, five nor-β-lapachone-based 1,2,3-triazoles and ten α-lapachone-based 1,2,3-triazoles. These and other naphthoquinonoid compounds were evaluated for their activity against promastigote forms of antimony-sensitive and -resistant strains of Leishmania infantum (syn. Leishmania chagasi) and Leishmania amazonensis. The toxicity of these compounds to mammalian cells was also examined. The substances were more potent than an antimonial drug, with IC50 values ranging from 1.0 to 50.7 μM. Nor-α-lapachone derivatives showed the highest antileishmanial activity, with selectivity indices in the range of 10-15. These compounds emerged as important leads for further investigation as antileishmanial agents. Additionally, one of these compounds exhibited cross-resistance in Sb-resistant Leishmania and could provide a molecular tool for investigating the multidrug resistance mechanisms in Leishmania parasites. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  1. Versatile convergent synthesis of a three peptide loop containing protein mimic of whooping cough pertactin by successive Cu(I)-catalyzed azide alkyne cycloaddition on an orthogonal alkyne functionalized TAC-scaffold

    NARCIS (Netherlands)

    Werkhoven, Paul R; van de Langemheen, Helmus; van der Wal, Steffen; Kruijtzer, John A W; Liskamp, Rob M J

    2014-01-01

    Synthetic mimics of discontinuous epitopes may have a wide range of potential applications, including synthetic vaccines and inhibition of protein-protein interactions. However, synthetic access to these relatively complex peptide molecular constructs is limited. This paper describes a versatile con

  2. Cycloaddition reactivity studies of first-row transition metal-azide complexes and alkynes: an inorganic click reaction for metalloenzyme inhibitor synthesis.

    Science.gov (United States)

    Evangelio, Emi; Rath, Nigam P; Mirica, Liviu M

    2012-07-14

    The studies described herein focus on the 1,3-dipolar cycloaddition reaction between first-row transition metal-azide complexes and alkyne reagents, i.e. an inorganic variant of the extensively used "click reaction". The reaction between the azide complexes of biologically-relevant metals (e.g., Fe, Co and Ni) found in metalloenzyme active sites and alkyne reagents has been investigated as a proof-of-principle for a novel method of developing metalloenzyme triazole-based inhibitors. Six Fe, Co and Ni mono-azide complexes employing salen- and cyclam-type ligands have been synthesized and characterized. The scope of the targeted inorganic azide-alkyne click reaction was investigated using the electron-deficient alkyne dimethyl acetylenedicarboxylate. Of the six metal-azide complexes tested, the Co and Ni complexes of the 1,4,8,11-tetrametyl-1,4,8,11-tetraazacyclotetradecane (Me(4)cyclam) ligand showed a successful cycloaddition reaction and formation of the corresponding metal-triazolate products, which were crystallographically characterized. Moreover, use of less electron deficient alkynes resulted in a loss of cycloaddition reactivity. Analysis of the structural parameters of the investigated metal-azide complexes suggests that a more symmetric structure and charge distribution within the azide moiety is needed for the formation of a metal-triazolate product. Overall, these results suggest that a successful cycloaddition reaction between a metal-azide complex and an alkyne substrate is dependent both on the ligand and metal oxidation state, that determine the electronic properties of the bound azide, as well as the electron deficient nature of the alkyne employed.

  3. Site-directed spin-labeling of DNA by the azide-alkyne 'click' reaction: nanometer distance measurements on 7-deaza-2'-deoxyadenosine and 2'-deoxyuridine nitroxide conjugates spatially separated or linked to a 'dA-dT' base pair.

    Science.gov (United States)

    Ding, Ping; Wunnicke, Dorith; Steinhoff, Heinz-Jürgen; Seela, Frank

    2010-12-27

    Nucleobase-directed spin-labeling by the azide-alkyne 'click' (CuAAC) reaction has been performed for the first time with oligonucleotides. 7-Deaza-7-ethynyl-2'-deoxyadenosine (1) and 5-ethynyl-2'-deoxyuridine (2) were chosen to incorporate terminal triple bonds into DNA. Oligonucleotides containing 1 or 2 were synthesized on a solid phase and spin labeling with 4-azido-2,2,6,6-tetramethylpiperidine 1-oxyl (4-azido-TEMPO, 3) was performed by post-modification in solution. Two spin labels (3) were incorporated with high efficiency into the DNA duplex at spatially separated positions or into a 'dA-dT' base pair. Modification at the 5-position of the pyrimidine base or at the 7-position of the 7-deazapurine residue gave steric freedom to the spin label in the major groove of duplex DNA. By applying cw and pulse EPR spectroscopy, very accurate distances between spin labels, within the range of 1-2 nm, were measured. The spin-spin distance was 1.8±0.2 nm for DNA duplex 17(dA*(7,10))⋅11 containing two spin labels that are separated by two nucleotides within one individual strand. A distance of 1.4±0.2 nm was found for the spin-labeled 'dA-dT' base pair 15(dA*(7))⋅16(dT*(6)). The 'click' approach has the potential to be applied to all four constituents of DNA, which indicates the universal applicability of the method. New insights into the structural changes of canonical or modified DNA are expected to provide additional information on novel DNA structures, protein interaction, DNA architecture, and synthetic biology.

  4. Moderating strain without sacrificing reactivity: design of fast and tunable noncatalyzed alkyne-azide cycloadditions via stereoelectronically controlled transition state stabilization.

    Science.gov (United States)

    Gold, Brian; Dudley, Gregory B; Alabugin, Igor V

    2013-01-30

    Recently, we have identified two strategies for selective transition state (TS) stabilization in catalyst-free azide/alkyne cycloadditions. In particular, the transition states for the formation of both 1,4- and 1,5-isomers can be stabilized via hyperconjugative assistance for the C···N bond formation, whereas the 1,5-TS can be stabilized via C-H···X H-bonding interactions. When the hyperconjugative assistance is maximized by the antiperiplanar arrangement of propargylic σ-acceptors relative to the forming bonds, the combination of these TS-stabilizing effects was predicted to lead to ~1 million fold acceleration of the cycloaddition with methyl azide. The present work investigated whether hyperconjugative assistance and H-bonding can be combined with strain activation for the design of even more reactive alkynes and whether reactivity can be turned "on demand." When stereoelectronic amplification is achieved by optimal positioning of σ-acceptors at the endocyclic bonds antiperiplanar to the breaking alkyne π-bonds, the stabilization of the bent alkyne geometry leads to a significant decrease in strain in cyclic alkynes without compromising their reactivity in alkyne-azide cycloadditions. The approach can be used in a modular fashion where the TS stabilizing effects are introduced sequentially until the desired level of reactivity is achieved. A significant increase in reactivity upon the protonation of an endocyclic NH-group suggests a new strategy for the design of click reactions triggered by a pH-change or introduction of an external Lewis acid.

  5. Functionalization of carbon nanotubes and other nanocarbons by azide chemistry

    Institute of Scientific and Technical Information of China (English)

    Jin Han; Chao Gao

    2010-01-01

    Following the conventional carbon allotropes of diamond and graphite, fullerene, carbon nanotubes (CNTs) and graphene as 0D, 1D and 2D graphitic macromolecules have been discovered recently in succession, declaring the unlimited potential of carbon-based nanomaterials and nanotechnology. Although CNTs exhibit significant potential applications in advanced materials and other fields due to their extraordinary mechanical strength and electrical/thermal conductivity properties, their low solubility, poor wettability and bad dispersibility in common solvents and solid matrices have limited their processing and applications. Thus, the attempt to achieve wettable/processable CNTs by functionalization has attracted increasing attention in both scientific and industrial communities. In recent years, azide chemistry has been demonstrated as a powerful means to covalently modify CNTs. It consists of two major approaches: click chemistry and nitrene chemistry, which both involve the usage of various azide compounds. The former one is based on highly reactive and stereospecifical Cu(I) catalyzed azide-alkyne cycloaddition reaction; the latter one is based on the electrophilic attack to unsaturated bonds of CNTs with nitrenes as reactive intermediates formed from thermolysis or photolysis of azides. In this mini-review paper, the azide chemistry to functionalize CNTs is highlighted and the corresponding functionalization routes to build CNT-based complex structures are also discussed. Besides, covalent functionalizations of other graphitic nanomaterials such as fullerence and graphene, via azide chemistry, are commented briefly.

  6. Synthesis and structural characterisation of (aryl-BIAN)copper(I) complexes and their application as catalysts for the cycloaddition of azides and alkynes.

    Science.gov (United States)

    Li, Lidong; Lopes, Patrícia S; Rosa, Vitor; Figueira, Cláudia A; Lemos, M Amélia N D A; Duarte, M Teresa; Avilés, Teresa; Gomes, Pedro T

    2012-05-07

    A series of Ar-BIAN-based copper(I) complexes (where Ar-BIAN = bis(aryl)acenaphthenequinonediimine) were synthesised and characterised by (1)H and (13)C NMR spectroscopies, FT-IR spectroscopy, MALDI-TOF-MS spectrometry, cyclic voltammetry and single crystal X-ray diffraction. The bis-chelated complexes of general formula [Cu(Ar-BIAN)(2)]BF(4) (where Ar = C(6)H(5) (1), 4-iPrC(6)H(4) (3), 2-iPrC(6)H(4) (4)) were prepared by reaction of [Cu(NCMe)(4)]BF(4) with two equivalents of the corresponding Ar-BIAN ligands, in dichloromethane, while the mono-chelated complexes of the type [Cu(Ar-BIAN)L(2)]BF(4) (where Ar = 2,6-iPr(2)C(6)H(3), L = PhCN (6); Ar = 4-iPrC(6)H(4), L = PPh(3) (7)) were readily accessible by treatment of [Cu(NCR)(4)]BF(4) (R = Me, Ph) with one equivalent of the corresponding Ar-BIAN ligands in the absence or presence of two equivalents of PPh(3), in the same solvent. The structures of complexes 3, 4, 6 and 7 were obtained by single crystal X-ray diffraction, showing distorted tetrahedral geometries around the copper centres in all cases. The electrochemical studies of these complexes and of the already reported [Cu(2,4,6-Me(3)C(6)H(2)-BIAN)(2)]BF(4) (2) and [Cu(2,6-iPr(2)C(6)H(3)-BIAN)(NCMe)(2)] (5), demonstrated that the bis-chelated complexes 1-4 undergo a reversible one-electron reduction or oxidation processes on copper, while the mono-chelated complexes 5-7 show a partially reversible oxidation and an irreversible reduction feature. Both kinds of (Ar-BIAN)copper(I) complexes are active catalysts for the copper(I)-catalysed azide-alkyne cycloaddition reaction (CuAAC). Complex 7, bearing PPh(3) ligands, exhibits the highest catalytic activity, which is comparable with that of the typical CuSO(4)-sodium ascorbate catalyst system.

  7. Direct Light-up of cAMP Derivatives in Living Cells by Click Reactions

    Directory of Open Access Journals (Sweden)

    Yan Xu

    2013-10-01

    Full Text Available 8-Azidoadenosine 3′,5′-cyclic monophosphate (8-azido cAMP was directly detected in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP derivatives by fluorescence light-up. Fluorescence emission was generated by two non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated cyclooctyne (DIFO reagent as a probe. The azide-alkyne cycloaddition reaction between 8-azido cAMP and DIFO induces fluorescence in 8-azido cAMP. The fluorescence emission serves as a way to probe 8-azido cAMP in cells.

  8. Orthogonally bifunctionalised polyacrylamide nanoparticles: a support for the assembly of multifunctional nanodevices

    Science.gov (United States)

    Giuntini, F.; Dumoulin, F.; Daly, R.; Ahsen, V.; Scanlan, E. M.; Lavado, A. S. P.; Aylott, J. W.; Rosser, G. A.; Beeby, A.; Boyle, R. W.

    2012-03-01

    Polyacrylamide nanoparticles bearing two orthogonal reactive functionalities were prepared by reverse microemulsion polymerisation. Water-soluble photosensitisers and peptide or carbohydrate moieties were sequentially attached to the new nanospecies by orthogonal conjugations based on copper-catalysed azide-alkyne cycloaddition and isothiocyanate chemistry.Polyacrylamide nanoparticles bearing two orthogonal reactive functionalities were prepared by reverse microemulsion polymerisation. Water-soluble photosensitisers and peptide or carbohydrate moieties were sequentially attached to the new nanospecies by orthogonal conjugations based on copper-catalysed azide-alkyne cycloaddition and isothiocyanate chemistry. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr11947a

  9. Efficient Förster resonance energy transfer in 1,2,3-triazole linked BODIPY-Zn(II) meso-tetraphenylporphyrin donor-acceptor arrays.

    Science.gov (United States)

    Leonardi, Matthew J; Topka, Michael R; Dinolfo, Peter H

    2012-12-17

    Cu(I) catalyzed azide-alkyne cycloaddition (CuAAC) reactivity was successfully employed to synthesize three donor-acceptor energy transfer (EnT) arrays that contain one (Dyad), three (Tetrad) and four (Pentad) 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) donors connected to a Zn-tetraphenylporphyrin acceptor via 1,2,3-triazole linkages. The photophysical properties of the three arrays, along with individual donor and acceptor chromophores, were investigated by UV-vis absorption and emission spectroscopy, fluorescence lifetimes, and density functional theory (DFT) electronic structure modeling. Comparison of the UV-vis absorption spectra and frontier molecular orbitals from DFT calculations of the three arrays with ZnTPP, ZnTTrzlP, and Trzl-BODIPY shows that the electronic structure of the chromophores is essentially unperturbed by the 1,2,3-triazole linkage. Time-dependent DFT (TDDFT) calculations on the Dyad reproduce the absorption spectra in THF and show no evidence of excited state mixing of the donor and acceptor. The BODIPY singlet excited state emission is significantly quenched in all three arrays, consistent with EnT to the porphyrin core, with efficiencies of 95.8, 97.5, and 97.2% for the Dyad, Tetrad, and Pentad, respectively. Fluorescence excitation spectra of the three arrays, measured at the porphyrin emission, mirror the absorption profile of both the porphyrin and BODIPY chromophores and are consistent with the Förster resonance energy transfer (FRET) mechanism. Applying Förster theory to the spectroscopic data of the chromophores gives EnT efficiency estimates that are in close agreement with experimental values, suggesting that the through-space mechanism plays a dominant role in the three arrays.

  10. 'Click' chemistry synthesis and capillary electrophoresis study of 1,4-linked 1,2,3-triazole AZT-systemin conjugate.

    Science.gov (United States)

    Dobkowski, Michał; Szychowska, Aleksandra; Pieszko, Małgorzata; Miszka, Anna; Wojciechowska, Monika; Alenowicz, Magdalena; Ruczyński, Jarosław; Rekowski, Piotr; Celewicz, Lech; Barciszewski, Jan; Mucha, Piotr

    2014-09-01

    The Cu(I) catalyzed Huisgen 1,3-dipolar azide-alkyne cycloaddition (CuAAC) was applied for a nucleoside-peptide bioconjugation. Systemin (Sys), an 18-aa plant signaling peptide naturally produced in response to wounding or pathogen attack, was chemically synthesized as its N-propynoic acid functionalized analog (Prp-Sys) using the SPPS. Next, CuAAC was applied to conjugate Prp-Sys with 3'-azido-2',3'-dideoxythymidine (AZT), a model cargo molecule. 1,4-Linked 1,2,3-triazole AZT-Sys conjugate was designed to characterize the spreading properties and ability to translocate of cargo molecules of systemin. CuAAC allowed the synthesis of the conjugate in a chemoselective and regioselective manner, with high purity and yield. The presence of Cu(I) ions generated in situ drove the CuAAC reaction to completion within a few minutes without any by-products. Under typical separation conditions of phosphate 'buffer' at low pH and uncoated fused bare-silica capillary, an increasing peak intensity assigned to triazole-linked AZT-Sys conjugate was observed using capillary electrophoresis (CE) during CuAAC. CE analysis showed that systemin peptides are stable in tomato leaf extract for up to a few hours. CE-ESI-MS revealed that the native Sys and its conjugate with AZT are translocated through the tomato stem and can be directly detected in stem exudates. The results show potential application of systemin as a transporter of low molecular weight cargo molecules in tomato plant and of CE method to characterize a behavior of plant peptides and its analogs.

  11. "Giant Surfactants" Created by the Fast and Efficient Functionalization of a DNA Tetrahedron with a Temperature-Responsive Polymer

    NARCIS (Netherlands)

    Wilks, Thomas R.; Bath, Jonathan; de Vries, Jan Willem; Raymond, Jeffery E.; Herrmann, Andreas; Turberfield, Andrew J.; O'Reilly, Rachel K.; O’Reilly, Rachel K.

    2013-01-01

    Copper catalyzed azide-alkyne cycloaddition (CuAAC) was employed to synthesize DNA block copolymers (DBCs) with a range of polymer blocks including temperature-responsive poly(N-isoproylacrylamide) (poly(NIPAM)) and highly hydrophobic poly(styrene). Exceptionally high yields were achieved at low DNA

  12. Glucose selective bis-boronic acid click-fluor.

    Science.gov (United States)

    Zhai, Wenlei; Male, Louise; Fossey, John S

    2017-02-14

    Four novel bis-boronic acid compounds were synthesised via copper catalysed azide-alkyne cycloaddition (CuAAC) reactions. Glucose selectivity was observed for a particular structural motif. Moreover, a new glucose selective fluorescent sensor was designed and synthesised as a result.

  13. Functionalization of Fatty Acid Vesicles through Newly Synthesized Bolaamphiphile-DNA Conjugates

    DEFF Research Database (Denmark)

    Wamberg, M. C.; Wieczorek, R.; Brier, S. B.

    2014-01-01

    of these structures, only one novel bola-amphiphile DNA conjugate could interact efficiently with or spontaneously pierce into the vesicle bilayers without jeopardizing their self-assembly or stability. This molecule was synthesized via a Cu(I)-catalyzed [3 + 2] azide-alkyne cycloaddition (click reaction...

  14. Carbon-rich "Click" 1,2,3-triazoles: hexaphenylbenzene and hexa-peri-hexabenzocoronene-based ligands for Suzuki-Miyaura catalysts.

    Science.gov (United States)

    Wright, James R; Crowley, James D; Lucas, Nigel T

    2016-10-27

    Hexaphenylbenzene (HPB) and hexa-peri-hexabenzocoronene-(HBC) functionalised 1,2,3-triazoles have been synthesised using an optimised copper(i)-catalysed azide-alkyne cycloaddition (CuAAC) reaction. The coordination chemistry of these ligands was explored through the synthesis of the respective palladium(ii) complexes and their activity as catalysts in the Suzuki-Miyaura reaction assessed.

  15. Two consecutive click reactions as a general route to functional cyclic polyesters.

    Science.gov (United States)

    Yuan, You-Yong; Du, Jin-Zhi; Wang, Jun

    2012-01-14

    A simple and universal route to functional cyclic polyesters has been demonstrated, combining two consecutive click reactions of azide-alkyne cycloaddition of linear hetero-bifunctional precursors and thiol-ene coupling for post cyclization functionalizations. Functional cationic and thermo-responsive cyclic polyphosphoesters have been synthesized to demonstrate the efficiency of the procedures.

  16. Conjugation of transferrin to azide-modified CdSe/ZnS core-shell quantum dots using cyclooctyne click chemistry.

    Science.gov (United States)

    Schieber, Christine; Bestetti, Alessandra; Lim, Jet Phey; Ryan, Anneke D; Nguyen, Tich-Lam; Eldridge, Robert; White, Anthony R; Gleeson, Paul A; Donnelly, Paul S; Williams, Spencer J; Mulvaney, Paul

    2012-10-15

    Twinkle twinkle quantum dot: Conjugation of biomolecules to azide-modified quantum dots (QDs) through a bifunctional linker, using strain-promoted azide-alkyne cycloaddition with the QD and a squaramide linkage to the biomolecule (see scheme). Transferrin-conjugated QDs were internalized by transferrin-receptor expressing HeLa cells.

  17. Nucleobase azide-ethynylribose click chemistry contributes to stabilizing oligonucleotide duplexes and stem-loop structures.

    Science.gov (United States)

    Kitamura, Yoshiaki; Asakura, Ryo; Terazawa, Koki; Shibata, Aya; Ikeda, Masato; Kitade, Yukio

    2017-06-15

    The formation of 1,4-disubstituted 1,2,3-triazoles through copper-catalyzed azide-alkyne cycloaddition (CuAAC) in oligonucleotides bearing 1-deoxy-1-ethynyl-β-d-ribofuranose (R(E)) can have a positive impact on the stability of oligonucleotide duplexes and stem-loop structures. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Heterogeneous catalysis through microcontact printing

    NARCIS (Netherlands)

    Spruell, Jason M.; Sheriff, Bonnie A.; Rozkiewicz, D.I.; Dichtel, William R.; Rohde, Rosemary D.; Reinhoudt, David; Stoddart, Fraser; Heath, James R.

    2008-01-01

    Minting a Stamp: The preparation of copper metal-coated elastomeric stamps and their use in catalyzing the Cu-catalyzed azide-alkyne cycloaddition reaction heterogeneously through microcontact printing is described. This StampCat process is compared to other conventional surface-functionalization te

  19. Functional silicone elastomers via novel siloxane copolymers and chain extenders

    DEFF Research Database (Denmark)

    Madsen, Frederikke Bahrt; Daugaard, Anders Egede; Hvilsted, Søren

    of siloxane copolymers[1] (via the tris(pentafluorophenyl)borane catalysed Piers-Rubinsztajn reaction[2]), which allows for the attachment of functional molecules through copper-catalysed azide-alkyne 1,3-dipolar cycloaddition (CuAAC)[3]. The synthesised copolymers allow for a high degree of chemical freedom...

  20. Functional silicone copolymers and elastomers with high dielectric permittivity

    DEFF Research Database (Denmark)

    Madsen, Frederikke Bahrt; Daugaard, Anders Egede; Hvilsted, Søren

    . This was done trough the synthesis of new functionalizable siloxane copolymers [2] that allow for the attachment of high dielectric permittivity molecules through copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reactions. The synthesised siloxane copolymers were prepared via the tris...

  1. Sulfonamide bearing oligonucleotides: Simple synthesis and efficient RNA recognition

    DEFF Research Database (Denmark)

    Kumar, P.; Chandak, N.; Nielsen, P.;

    2012-01-01

    Four pyrimidine nucleosides wherein a benzensulfonamide group is linked to the C-5 position of the uracil nucleobase through a triazolyl or an alkynyl linker were prepared by Cu(I)-assisted azide-alkyne cycloadditions (CuAAC) or Sonogashira reactions, respectively, and incorporated into oligonucl...

  2. Interfacing click chemistry with automated oligonucleotide synthesis for the preparation of fluorescent DNA probes containing internal xanthene and cyanine dyes

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Wengel, Jesper

    2013-01-01

    for the first time performed solid-phase copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click labeling during the automated phosphoramidite oligonucleotide synthesis followed by postsynthetic click reactions in solution. We demonstrate that our novel strategy is rapid and efficient for the preparation...

  3. On-Surface Synthesis by Click Chemistry Investigated by STM and XPS

    DEFF Research Database (Denmark)

    Vadapoo, Sundar Raja

    2014-01-01

    such as molecular electronics and surface functionalization. In this thesis, a well-defined click chemistry approach is followed, with the study of azide-alkyne cycloaddition on Cu(111) surface in UHV environment. A successful achievement of the click reaction product via on-surface synthesis has been shown, which...

  4. Cucurbit[6]uril-Promoted Click Chemistry for Protein Modification.

    Science.gov (United States)

    Finbloom, Joel A; Han, Kenneth; Slack, Clancy C; Furst, Ariel L; Francis, Matthew B

    2017-07-19

    Azide-alkyne cycloaddition is a powerful reaction for the formation of bioconjugates. When catalyzed by Cu(I) or strain promotion, this cycloaddition is considered to be a "click" reaction with many applications in chemical biology and materials science. We report a new type of azide-alkyne click chemistry for the synthesis of protein conjugates using cucurbit[6]uril (CB6) supramolecular chemistry. CB6-promoted azide-alkyne cycloaddition has been previously used for the synthesis of rotaxanes but has not been applied to the development of complex bioconjugates. By developing new substrates for CB6 click that do not contain any cross-reactive functional groups and by optimizing reaction conditions, we converted CB6 click chemistry from a rotaxane synthesis tool into a useful bioconjugation technique. Using these new parameters, we synthesized a series of protein conjugates including protein-peptide, protein-DNA, protein-polymer, and protein-drug conjugates. We further demonstrated that CB6 click can be used in conjunction with strain-promoted azide-alkyne cycloaddition to generate distinct bioconjugates in protein mixtures. CB6 click is a promising new reaction for the development of protein conjugates and can be applied toward the synthesis of complex biomaterials for a wide range of applications.

  5. Intramolecular Cycloaddition of Imines of Cysteine Derivatives

    Directory of Open Access Journals (Sweden)

    Teresa M. V. D. Pinho e Melo

    1998-02-01

    Full Text Available Azomethine ylides were generated from Schiffs bases of S-allylcysteine methyl ester and their intramolecular 1,3-dipolar cycloadditions were studied. These reactions led to the synthesis of thieno[3,4-b]pyrrole derivatives in good yield.

  6. An efficient synthesis of isocoumarins via a CuI catalyzed cascade reaction process

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    3-Alkyl isocoumarins are provided by CuI/amino acid-catalyzed Sonogashira coupling reaction of o-bromo benzoic acids and terminal alkynes and the subsequent additive cyclization. This cascade process allows synthesis of diverse isocoumarins by varying both coupling partners bearing a wide range of functional groups.

  7. Crosslinking of Kapok Cellulose Fiber via Azide Alkyne Click Chemistry as a New Material for Filtering System: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Nur Syazwani Abd Rahman

    2016-01-01

    Full Text Available A new class of green material has been elaborated by grafting the modified kapok fiber, by the means of azidated kapok fiber followed by “click-chemistry” reaction with the terminal alkyne crosslinker. The modified and synthesized product was characterized using Fourier transform infrared spectroscopy (FT-IR, and Scanning electron microscopy (SEM. The study also was undertaken to investigate the effect on the absorption of methylene blue from aqueous solution onto the click fiber prepared. The findings showed that the click kapok absorbed more compared to the untreated kapok. Based on the result, the reaction of click chemistry influenced the properties of the filter made from kapok fiber.

  8. Simple and efficient synthesis of 5'-aryl-5'-deoxyguanosine analogs by azide-alkyne click reaction and their antileishmanial activities.

    Science.gov (United States)

    Daligaux, Pierre; Pomel, Sébastien; Leblanc, Karine; Loiseau, Philippe M; Cavé, Christian

    2016-05-01

    A series of non-hydrolysable 5'-aryl substituted GDP analogs has been synthesized by reacting 5'-azido-5'-deoxyguanosine with different aryl- and benzyloxy-alkynes. Cu(I) nanoparticles in water were found to be the most efficient catalyst, producing the desired 5'-arylguanosines with good yields. The synthesized compounds were screened for in vitro antileishmanial activity against Leishmania donovani axenic amastigotes and intramacrophage amastigotes stages. The 4-(3-nitrobenzyl)-1,2,3-triazole 5'-substituted guanosine analog was found to be the most active in the series with an IC50 of 8.6 μM on axenic amastigotes. Despite a rather low in vitro antileishmanial activity on the intramacrophage amastigotes, the absence of cytotoxicity on RAW 264.7 macrophages justifies further pharmacomodulations making this antileishmanial series promising.

  9. Enatioselective[2+2+2] Cycloaddition as A Synthetic Tool

    Institute of Scientific and Technical Information of China (English)

    T.Shibata; S.Yoshida; M.Otsuka; Y.Arai; K.Endo

    2007-01-01

    1 Results Transition metal-catalyzed [2+2+2] cycloaddition is one of the most efficient protocols for the construction of six-membered ring system.Our group has comprehensively studied various types of highly enantioselective [2+2+2] cycloaddition for the synthesis of chiral cycloadducts; we already reported an iridium-catalyzed intermolecular [2+2+2] cycloaddition between α,ω-diynes,having various tethers and substituents on the alkyne termini,and monoalkynes,possessing oxygen or/and nitrogen functiona...

  10. Synthesis and characterization of sugar based low molecular weight gelators and the preparation of chiral sulfinamides

    Science.gov (United States)

    Mangunuru, Hari Prasad Reddy

    Low molecular weight gelators (LMWGs) have received considerable attention in the field of chemistry from last few decades. These compounds form self-assembled fibrous networks like micelles, cylindrical, sheets, fibers, layers and so on. The fibrous network entraps the solvent and forms gel, because of the self-assembly phenomenon and their demonstrated potential uses in a variety of areas, ranging from environmental to medicinal applications. Sugars are good starting materials to synthesize the new class of LMWG's, because these are different from some expensive materials, these are natural products. We have synthesized and characterized the LMGS's based on D-glucose and D-glucosamine. D-glucosamine is the versatile starting material to make different peptoids and triazoles. Several series of compounds were synthesized using compounds 1-3 as starting material and studied the gelation behavior all the compounds. We have studied the self-assembling properties of a new class of tripeptoids, synthesized by one-pot Ugi reaction from simple starting materials. Among the focused library of tripeptoids synthesized, we found that several efficient low molecular weight organogelators were obtained for aqueous DMSO and ethanol mixtures. We have also synthesized and characterized a series of monosaccharide triazole derivatives. These compounds were synthesized from N-acetyl glucosamine and D-glucose via a Cu(I) catalyzed azide/alkyne cycloaddition reaction (CuAAc). The compounds have been screened for their gelation properties and several efficient low molecular weight organo/hydro gelators were obtained, among these compounds, five per-acetyl glucosamine derivatives and one peracetyl glucose derivative were able to form gels in water. These new molecules are expected to be useful in drug delivery and tissue engineering.*. Asymmetric synthesis of chiral amines is a challenging in synthetic organic chemistry. The development of new catalysts for asymmetric organic

  11. Gold-catalyzed oxidative cycloadditions to activate a quinoline framework.

    Science.gov (United States)

    Huple, Deepak B; Ghorpade, Satish; Liu, Rai-Shung

    2013-09-23

    Going for gold! Gold-catalyzed reactions of 3,5- and 3,6-dienynes with 8-alkylquinoline oxides results in an oxidative cycloaddition with high stereospecificity (see scheme; EWG = electron-withdrawing group); this process involves a catalytic activation of a quinoline framework. The reaction mechanism involves the intermediacy of α-carbonyl pyridinium ylides (I) in a concerted [3+2]-cycloaddition with a tethered alkene.

  12. Switchable regioselectivity in amine-catalysed asymmetric cycloadditions

    Science.gov (United States)

    Zhou, Zhi; Wang, Zhou-Xiang; Zhou, Yuan-Chun; Xiao, Wei; Ouyang, Qin; Du, Wei; Chen, Ying-Chun

    2017-06-01

    Building small-molecule libraries with structural and stereogenic diversity plays an important role in drug discovery. The development of switchable intermolecular cycloaddition reactions from identical substrates in different regioselective fashions would provide an attractive protocol. However, this also represents a challenge in organic chemistry, because it is difficult to control regioselectivity to afford the products exclusively and at the same time achieve high levels of stereoselectivity. Here, we report the diversified cycloadditions of α‧-alkylidene-2-cyclopentenones catalysed by cinchona-derived primary amines. An asymmetric γ,β‧-regioselective intermolecular [6+2] cycloaddition reaction with 3-olefinic (7-aza)oxindoles is realized through the in situ generation of formal 4-aminofulvenes, while a different β,γ-regioselective [2+2] cycloaddition reaction with maleimides to access fused cyclobutanes is disclosed. In contrast, an intriguing α,γ-regioselective [4+2] cycloaddition reaction is uncovered with the same set of substrates, by employing an unprecedented dual small-molecule catalysis of amines and thiols. All of the cycloaddition reactions exhibit excellent regio- and stereoselectivity, producing a broad spectrum of chiral architectures with high structural diversity and molecular complexity.

  13. Synthesis and characterization of cyclic polystyrene using copper-catalyzed alkyne-azide cycloaddition coupling - evaluation of physical properties and optimization of cyclization conditions

    Science.gov (United States)

    Elupula, Ravinder

    Polymers with a cyclic topology exhibit a range of unique and potentially useful physical properties, including reduced rates of degradation and increased rates of diffusion in bulk relative to linear analogs. However the synthesis of high purity cyclic polymers, and verification of their structural purity remains challenging. The copper-catalyzed azide-alkyne "click" cyclization route toward cyclic polymers has been used widely, due to its synthetic ease and its compatibility with diverse polymer backbones. Yet unoptimized click cyclization conditions have been observed to generate oligomeric byproducts. In order to optimize these cyclization conditions, and to better understand the structure of the higher molecular weight oligomers, these impurities have been isolated by size exclusion chromatography (SEC) and characterized by mass spectrometry (MS). Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-ToF) MS is a particularly valuable characterization tool and was used to determine that the high molecular weight impurities are predominantly cyclic oligomers. It should also be noted that the rapid analysis and small analyte requirements of this MS technique make it particularly attractive as a general tool for elucidating polymer architecture. Ability to tailor the physical properties of polymers by changing the architecture alone has garnered a lot of attention over the past few decades. Compared to their linear analogues, these novel polymer architectures behave completely different in nanoscale regime. Cyclic polymers are especially intriguing since we can compare the differences in the physical properties with that of the linear chains. One of the major physical property changes are T g-confinement effect. Using ATRP and "click chemistry" we have produced highly pure cyclic PS (c-PS) with number-average molecular weight (MW) of 3.4 kg/mol and 9.1 kg/mol. Bulk glass transition temperatures for c-PS were weakly depended on MWs

  14. Reactivity mapping with electrochemical gradients for monitoring reactivity at surfaces in space and time.

    Science.gov (United States)

    Krabbenborg, Sven O; Nicosia, Carlo; Chen, Pengkun; Huskens, Jurriaan

    2013-01-01

    Studying and controlling reactions at surfaces is of great fundamental and applied interest in, among others, biology, electronics and catalysis. Because reaction kinetics is different at surfaces compared with solution, frequently, solution-characterization techniques cannot be used. Here we report solution gradients, prepared by electrochemical means, for controlling and monitoring reactivity at surfaces in space and time. As a proof of principle, electrochemically derived gradients of a reaction parameter (pH) and of a catalyst (Cu(I)) have been employed to make surface gradients on the micron scale and to study the kinetics of the (surface-confined) imine hydrolysis and the copper(I)-catalysed azide-alkyne 1,3-dipolar cycloaddition, respectively. For both systems, the kinetic data were spatially visualized in a two-dimensional reactivity map. In the case of the copper(I)-catalysed azide-alkyne 1,3-dipolar cycloaddition, the reaction order (2) was deduced from it.

  15. Patterned porous silicon photonic crystals with modular surface chemistry for spatial control of neural stem cell differentiation

    Science.gov (United States)

    Huang, Tiffany H.; Pei, Yi; Zhang, Douglas; Li, Yanfen; Kilian, Kristopher A.

    2016-05-01

    We present a strategy to spatially define regions of gold and nanostructured silicon photonics, each with materials-specific surface chemistry, for azide-alkyne cycloaddition of different bioactive peptides. Neural stem cells are spatially directed to undergo neurogenesis and astrogenesis as a function of both surface properties and peptide identity.We present a strategy to spatially define regions of gold and nanostructured silicon photonics, each with materials-specific surface chemistry, for azide-alkyne cycloaddition of different bioactive peptides. Neural stem cells are spatially directed to undergo neurogenesis and astrogenesis as a function of both surface properties and peptide identity. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr08327c

  16. The growing impact of bioorthogonal click chemistry on the development of radiopharmaceuticals.

    Science.gov (United States)

    Zeng, Dexing; Zeglis, Brian M; Lewis, Jason S; Anderson, Carolyn J

    2013-06-01

    Click chemistry has become a ubiquitous chemical tool with applications in nearly all areas of modern chemistry, including drug discovery, bioconjugation, and nanoscience. Radiochemistry is no exception, as the canonical Cu(I)-catalyzed azide-alkyne cycloaddition, strain-promoted azide-alkyne cycloaddition, inverse electron demand Diels-Alder reaction, and other types of bioorthogonal click ligations have had a significant impact on the synthesis and development of radiopharmaceuticals. This review will focus on recent applications of click chemistry ligations in the preparation of imaging agents for SPECT and PET, including small molecules, peptides, and proteins labeled with radionuclides such as (18)F, (64)Cu, (111)In, and (99m)Tc.

  17. Chemical Architecture and Applications of Nucleic Acid Derivatives Containing 1,2,3-Triazole Functionalities Synthesized via Click Chemistry

    Directory of Open Access Journals (Sweden)

    Wei Gong

    2012-10-01

    Full Text Available There is considerable attention directed at chemically modifying nucleic acids with robust functional groups in order to alter their properties. Since the breakthrough of copper-assisted azide-alkyne cycloadditions (CuAAC, there have been several reports describing the synthesis and properties of novel triazole-modified nucleic acid derivatives for potential downstream DNA- and RNA-based applications. This review will focus on highlighting representative novel nucleic acid molecular structures that have been synthesized via the “click” azide-alkyne cycloaddition. Many of these derivatives show compatibility for various applications that involve enzymatic transformation, nucleic acid hybridization, molecular tagging and purification, and gene silencing. The details of these applications are discussed. In conclusion, the future of nucleic acid analogues functionalized with triazoles is promising.

  18. Peptoids and polyamines going sweet: Modular synthesis of glycosylated peptoids and polyamines using click chemistry

    Directory of Open Access Journals (Sweden)

    Daniel Fürniss

    2013-01-01

    Full Text Available Sugar moieties are present in a wide range of bioactive molecules. Thus, having versatile and fast methods for the decoration of biomimetic molecules with sugars is of fundamental importance. The glycosylation of peptoids and polyamines as examples of such biomimetic molecules is reported here. The method uses Cu-catalyzed azide alkyne cycloaddition to promote the reaction of azidosugars with either polyamines or peptoids. In addition, functionalized nucleic acids were attached to polyamines via the same route. Based on a modular solid-phase synthesis of peralkynylated peptoids with up to six alkyne groups, the latter were modified with azidosugar building blocks by using copper-catalyzed azide alkyne cycloadditions. In addition, the up-scaling of some particular azide-modified sugars is described.

  19. Synthesis and Fluorescence Properties of Coumarin Glycosides and Triazoylglycosides

    Institute of Scientific and Technical Information of China (English)

    WU Zheng; FU Xin-ling; YANG Nan; WANG Qiu-an

    2013-01-01

    Four coumarin glycosides(1-4) and four coumarin triazoylglycosides(5-8) were synthesized by phase transfer catalytic glycosylation and copper-catalyzed azide-alkyne cycloaddition(CuAAC) respectively from 4-methyl-7-hydroxyl coumarin(4-methylumbelliferone).The structures were characterized by 1H NMR,MS or IR.The fluorescent properties of the coumarin glycosides and triazoylglycosides were studied in different solvents and compared to those of 4-methyl-7-hydroxyl coumarin.

  20. Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

    Directory of Open Access Journals (Sweden)

    Camilla Matassini

    2015-12-01

    Full Text Available The synthesis of new multivalent architectures based on a trihydroxypiperidine α-fucosidase inhibitor is reported herein. Tetravalent and nonavalent dendrimers were obtained by means of the click chemistry approach involving the copper azide-alkyne-catalyzed cycloaddition (CuAAC between suitable scaffolds bearing terminal alkyne moieties and an azido-functionalized piperidine as the bioactive moiety. A preliminary biological investigation is also reported towards commercially available and human glycosidases.

  1. Unique tetrameric and hexameric mannoside clusters prepared by click chemistry.

    Science.gov (United States)

    Al-Mughaid, Hussein; Al-Zoubi, Raed M; Paul, Nawal K; Grindley, T Bruce

    2015-11-19

    The synthesis of novel tetrameric and hexameric mannoside clusters bearing 1,2,3-trizole linkages via Cu(I)-catalyzed azide-alkyne cycloaddition reaction ("click chemistry") is described. An attractive feature of these multiarmed mannoside clusters as potential inhibitors of uropathogenic Escherichia coli is the use of an aglycone whose length is designed to fit in the tyrosine gate. The acetylated mannosides were deprotected and the corresponding de-O-acetylated mannosides were found to exhibit good water solubility.

  2. Copper Supported on the SiO2 Nanoparticle in Click Chemistry: An Alternative Catalytic System for Regioselective and One-Pot Synthesis of 1,2,3-Triazoles and β-Hydroxytriazoles%Copper Supported on the SiO2 Nanoparticle in Click Chemistry: An Alternative Catalytic System for Regioselective and One-Pot Synthesis of 1,2,3-Triazoles and β-Hydroxytriazoles

    Institute of Scientific and Technical Information of China (English)

    Ciyabi Hashjin, Maryam; Ciyabi, Roghayeh; Baharloui, Maryam; Hosseini, Ghaffar; Tavakoli, Hamed

    2012-01-01

    In this work, readily prepared copper supported on the SiO2 nanoparticles has been found to effectively catalyze the 1,3-dipolar cycloaddition of a variety of azides, alkynes, epoxides and sodium azide, furnishing the correspond- ing 1,2,3-triazoles and β-hydroxytriazoles. Click reaction proceeds in short reaction times and under mild reaction conditions, and the resulting products are obtained in good yields at ambient temperature.

  3. Synthesis of 4-Alkylamino-2-Triazolylquinazolines

    Directory of Open Access Journals (Sweden)

    Goliškina Svetlana Marija

    2017-05-01

    Full Text Available 5-Alkylamino derivatives of tetrazolo[1,5-a]quinazoline were obtained with high regioselectivity in the reaction of 5-azidotetrazolo[1,5-a]quinazoline (formally, 2,4-diazidoquinazoline with long chain alkylamines. The obtained 5-aminoquinazoline derivatives were used in a copper catalyzed azide-alkyne 1,3-dipolar cycloaddition reaction to obtain series of 4-(alkylamino-2-(1,2,3-triazol-1-ylquinazolines.

  4. CuAAC click functionalization of azide-modified nanodiamond with a photoactivatable CO-releasing molecule (PhotoCORM) based on [Mn(CO)3(tpm)]+.

    Science.gov (United States)

    Dördelmann, G; Meinhardt, Thomas; Sowik, Thomas; Krueger, Anke; Schatzschneider, Ulrich

    2012-12-01

    The copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) was used for the first time to attach a biologically active carbon monoxide delivery agent to modified nanodiamond (ND) as a highly biocompatible carrier. The [Mn(CO)(3)(tpm)](+) photoactivatable CO-releasing molecule (PhotoCORM) on the surface retained the carbon monoxide release properties of the parent compound as shown with the myoglobin assay.

  5. Phase-vanishing method with acetylene evolution and its utilization in several organic syntheses.

    Science.gov (United States)

    Matake, Ryosuke; Niwa, Yuki; Matsubara, Hiroshi

    2015-05-15

    A novel quadraphasic phase-vanishing system in which acetylene is evolved from calcium carbide and directly applied in situ to the Sonogashira coupling reaction was developed. This method, which provides a safe, convenient, and one-pot means to utilize gaseous reagents without special equipment, was also applied to a Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and a three-component aldehyde-alkyne-amine (A(3)) coupling reaction with excellent results.

  6. A Template-Mediated Click-Click Reaction: PNA-DNA, PNA-PNA (or Peptide) Ligation, and Single Nucleotide Discrimination

    OpenAIRE

    Peng, Xiaohua; Li, Hong; Seidman, Michael

    2010-01-01

    A highly efficient chemical ligation was developed for quantitative conjugation of PNA with DNA (PNA or peptide) using the copper-catalyzed azide-alkyne cycloaddition reaction. While PNAs with an alkyne at the C-terminus and an azide at the N-terminus have been used, an efficient click-click reaction occurs. The PNA click ligation is sequence-specific and capable of single nucleotide discrimination.

  7. Facile route for the regioselective synthesis of 1,4-disubstituted 1,2,3-triazole using copper nanoparticles supported on nanocellulose as recyclable heterogeneous catalyst

    Indian Academy of Sciences (India)

    MITALI CHETIA; ABDUL A ALI; ANKUR BORDOLOI; DIGANTA SARMA

    2017-08-01

    In this work, a green and efficient methodology has been developed for the synthesis of 1,2,3-triazoles by ‘copper nanoparticles supported on nanocellulose (CuNPs/NC)-catalyzed azide-alkyne cycloaddition reaction in glycerol, an environmentally benign solvent, with excellent yields. The present catalyst wascharacterized by TEM, XRD, SEM-EDX and FT-IR spectroscopy. The reusability of the prepared nanocatalyst was examined up to five times without significant loss of catalytic activity.

  8. Neutral Diboron Analogues of Archetypal Aromatic Species by Spontaneous Cycloaddition.

    Science.gov (United States)

    Arrowsmith, Merle; Böhnke, Julian; Braunschweig, Holger; Celik, Mehmet Ali; Claes, Christina; Ewing, William C; Krummenacher, Ivo; Lubitz, Katharina; Schneider, Christoph

    2016-09-05

    Among the numerous routes organic chemists have developed to synthesize benzene derivatives and heteroaromatic compounds, transition-metal-catalyzed cycloaddition reactions are the most elegant. In contrast, cycloaddition reactions of heavier alkene and alkyne analogues, though limited in scope, proceed uncatalyzed. In this work we present the first spontaneous cycloaddition reactions of lighter alkene and alkyne analogues. Selective addition of unactivated alkynes to boron-boron multiple bonds under ambient conditions yielded diborocarbon equivalents of simple aromatic hydrocarbons, including the first neutral 6 π-aromatic diborabenzene compound, a 2 π-aromatic triplet biradical 1,3-diborete, and a phosphine-stabilized 2 π-homoaromatic 1,3-dihydro-1,3-diborete. DFT calculations suggest that all three compounds are aromatic and show frontier molecular orbitals matching those of the related aromatic hydrocarbons, C6 H6 and C4 H4 (2+) , and homoaromatic C4 H5 (+) .

  9. 1,3-Dipolar cycloaddition of azomethine ylide from Phtaloylimidophenylalanyl-2-hydroxymethylaziridine1,3-Dipolar cycloaddition of azomethine ylide from Phtaloylimidophenylalanyl-2-hydroxymethylaziridine

    National Research Council Canada - National Science Library

    Assia Keniche; Wassila Drici; Mohamed Zakaria Slimani; Abdelmoumen Mezrai; Joseph Kajima Mulengi

    2013-01-01

    Phtaloylimidophenylalanyl-2-hydroxymethylaziridine has been used as a starting material to yield azomethine ylide through thermal opening and was then involved into 1,3-dipolar cycloaddition reactions...

  10. Recent developments in gold-catalyzed cycloaddition reactions

    Directory of Open Access Journals (Sweden)

    Fernando López

    2011-08-01

    Full Text Available In the last years there have been extraordinary advances in the development of gold-catalyzed cycloaddition processes. In this review we will summarize some of the most remarkable examples, and present the mechanistic rational underlying the transformations.

  11. Functionalization of Graphene via 1,3-Dipolar Cycloaddition

    NARCIS (Netherlands)

    Quintana, Mildred; Spyrou, Konstantinos; Grzelczak, Marek; Browne, Wesley R.; Rudolf, Petra; Prato, Maurizio

    Few-layer graphenes (FLG) produced by dispersion and exfoliation of graphite in N-methylpyrrolidone were successfully functionalized using the 1,3-dipolar cycloaddition of azomethine ylides. The amino functional groups attached to graphene sheets were quantified by the Kaiser test. These amino

  12. Functionalization of Graphene via 1,3-Dipolar Cycloaddition

    NARCIS (Netherlands)

    Quintana, Mildred; Spyrou, Konstantinos; Grzelczak, Marek; Browne, Wesley R.; Rudolf, Petra; Prato, Maurizio

    2010-01-01

    Few-layer graphenes (FLG) produced by dispersion and exfoliation of graphite in N-methylpyrrolidone were successfully functionalized using the 1,3-dipolar cycloaddition of azomethine ylides. The amino functional groups attached to graphene sheets were quantified by the Kaiser test. These amino group

  13. Direct Evidence of a Dinuclear Copper Intermediate in Cu(I)-Catalyzed Azide–Alkyne Cycloadditions

    OpenAIRE

    Worrell, B. T.; Malik, J.A.; FOKIN, V.V.

    2013-01-01

    The copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) has become a commonly employed method for the synthesis of complex molecular architectures under challenging conditions. Despite the widespread use of copper-catalyzed cycloaddition reactions, the mechanism of these processes has remained difficult to establish due to the involvement of multiple equilibria between several reactive intermediates. Real-time monitoring of a representative cycloaddition process via heat flow reaction calo...

  14. Synthesis of Spiroisoxazolines by 1,3-Dipolar Cycloaddition

    Directory of Open Access Journals (Sweden)

    Peter Ertl

    1997-04-01

    Full Text Available The cycloaddition of the chiral nitrile oxide 1 to 1-R-substituted 3,3-methylene-5,5-dimethyl-2-pyrrolidinones 2 (where R is H, n-butyl-, 1,1-dimethylethoxycarbonyl-, 1-methylethenyl- and acetyl- proceeds regioselectively under the formation of spiroisoxazolines, namely 7-R-substituted-6-oxo-8,8-dimethyl-1-oxa-2,7-diazaspiro[4,4]non-2-enes 5 and 6. The asymmetric induction expected by the a-chiral centre of the nitrile oxide 1 was not very effective, diastereoisomers 5 and 6 were formed in an approximate 50:50 ratio. The stereoselectivity of the 1,3-dipolar cycloaddition of the arylnitrile oxide 7 with the chiral lactam 3 and the achiral lactone 4 are investigated. The attack of the 1,3-dipole occurred from the less hindered face of the dipolarophile 3 and 4, giving the major isomer 8 and 10, respectively.

  15. Halo substituent effects on intramolecular cycloadditions involving furanyl amides.

    Science.gov (United States)

    Padwa, Albert; Crawford, Kenneth R; Straub, Christopher S; Pieniazek, Susan N; Houk, K N

    2006-07-21

    Intramolecular Diels-Alder reactions involving a series of N-alkenyl-substituted furanyl amides were investigated. Stable functionalized oxanorbornenes were formed in high yield upon heating at 80-110 degrees C. The cycloaddition reactions include several bromo-substituted furanyl amides, and these systems were found to proceed at a much faster rate and in higher yield than without substitution. This effect was observed by incorporating a halogen in the 3- or 5-position of the furan ring and appears to be general. The origin of increased cycloaddition rates for halo-substituted furans has been investigated with quantum mechanical calculations. The success of these reactions is attributed to increases in reaction exothermicities; this both decreases activation enthalpies and increases barriers to retrocycloadditions. Halogen substitution on furan increases reactant energy and stabilizes the product, which is attributed to the preference of electronegative halogens to be attached to a more highly alkylated and therefore more electropositive framework.

  16. Criss-cross Cycloadditions on Ketazines Derived from Alicyclic Ketones

    Directory of Open Access Journals (Sweden)

    Milan Potacek

    2006-01-01

    Full Text Available The reactivity of alicyclic ketazines in criss-cross cycloadditions was investigated. They react with potassium cyanate and ammonium thiocyanate in the presence of acetic acid to form spirocyclic perhydro[1,2,4]triazolo[1,2-a][1,2,4]triazole-1,5-diones and perhydro[1,2,4]triazolo[1,2-a][1,2,4]triazole-1,5-dithiones, respectively, in relatively high yields.

  17. Staudinger ketene-imine cycloaddition, RCM approach to macrocrocyclic bisazetidinones.

    Science.gov (United States)

    Ibrahim, Yehia A; Al-Azemi, Talal F; Abd El-Halim, Mohamed D; John, Elizabeth

    2009-06-05

    Application of Staudinger ketene-imine cycloaddition reaction to bis-o-allyloxyarylideneamines afforded the corresponding bisallyloxyazetidinones as the cis-cis diastereomers, exclusively obtained as a mixture of cis-syn-cis and cis-anti-cis. RCM of the latter using Grubbs' catalysts afforded the corresponding macrocyclic bisazetidinones in good yields. The cis-anti-cis bisazetidinones are readily identified by (1)H NMR using Eu(hfc)(3) chiral shift reagent.

  18. ORGANIC CHEMISTRY. Iron-catalyzed intermolecular [2+2] cycloadditions of unactivated alkenes.

    Science.gov (United States)

    Hoyt, Jordan M; Schmidt, Valerie A; Tondreau, Aaron M; Chirik, Paul J

    2015-08-28

    Cycloadditions, such as the [4+2] Diels-Alder reaction to form six-membered rings, are among the most powerful and widely used methods in synthetic chemistry. The analogous [2+2] alkene cycloaddition to synthesize cyclobutanes is kinetically accessible by photochemical methods, but the substrate scope and functional group tolerance are limited. Here, we report iron-catalyzed intermolecular [2+2] cycloaddition of unactivated alkenes and cross cycloaddition of alkenes and dienes as regio- and stereoselective routes to cyclobutanes. Through rational ligand design, development of this base metal-catalyzed method expands the chemical space accessible from abundant hydrocarbon feedstocks.

  19. Novel cross-linkers for PDMS networks for controlled and well distributed grafting of functionalities by click chemistry

    DEFF Research Database (Denmark)

    Bahrt, Frederikke; Dimitrov, Ivaylo; Daugaard, Anders Egede

    2013-01-01

    An azide-containing, trifunctional vinyl cross-linker for silicone networks has been synthesized. The cross-linker has through Cu(i) catalyzed 1,3-cycloaddition been reacted with six different alkyne-containing chemical groups which each possess a particular functionality. The functional cross-li...... The Royal Society of Chemistry....

  20. Iron-catalyzed Rearrangements and Cycloaddition Reactions of 2H-Chromenes

    Science.gov (United States)

    Luan, Yi; Sun, Huan

    2014-01-01

    Iron(III) salts catalyse the tandem rearrangement/hetero-Diels—Alder reaction of 2H-chromenes to yield tetrahydrochromeno heterocycles. The process can occur as a homodimerization and cycloaddition process using electron rich dienophiles. Deuterium labeling and mechanistic studies revealed a hydride shift and ortho-quinone methide cycloaddition reaction pathway. PMID:22098535

  1. Regioselective de novo synthesis of cyanohydroxypyridines with a concerted cycloaddition mechanism.

    Science.gov (United States)

    Lu, Jin-Yong; Keith, John A; Shen, Wei-Zheng; Schürmann, Markus; Preut, Hans; Jacob, Timo; Arndt, Hans-Dieter

    2008-10-08

    An efficient cycloaddition reaction of 1-alkoxy-1-azadienes with alpha,alpha-dicyanoalkenes is described, which gives facile access to highly substituted 3-hydroxypyridines in very good yields and with complete regiocontrol and chemoselectivity. The reaction path was investigated in detail by quantum mechanics calculations, reporting that a concerted cycloaddition mechanism and thermodynamic control synergistically contribute to the observed selectivity.

  2. Isocyanide based [4+1] cycloaddition reactions: an indispensable tool in multi-component reactions (MCRs).

    Science.gov (United States)

    Kaur, Tanpreet; Wadhwa, Preeti; Bagchi, Sourav; Sharma, Anuj

    2016-05-19

    The advent of cycloaddition reactions in the synthesis of heterocycles and their ever burgeoning applications in the fields of material chemistry, catalysis and drugs have been a profound scientific development. In particular, isocyanide based cycloaddition reactions have been harbingers of an exciting new chapter in the realms of organic synthesis. The emergence of numerous synthetic protocols utilizing formal cycloaddition of isocyanides with conjugated heterodienes has unleashed countless opportunities to design and synthesize diverse heterocyclic scaffolds. To date, there has not been any exclusive review on a formal [4+1] cycloaddition involving isocyanides. The present review highlights the journey of formal [4+1] cycloaddition reactions of isocyanides with diverse electrophilic substrates viz. oxadienes, azadienes, thioacyl imines, alkylidene amides, alkylidene hydrazines, α,β-unsaturated nitro compounds, α-thioxothioamides, nitroso alkenes, acyl imines, vinyl ketenes, vinyl isocyanates, etc. to afford functionalized pyrroles, imidazoles, furans, oxazoles, pyrazoles, etc.

  3. A copper(I)-catalyzed three-component domino process: assembly of complex 1,2,3-triazolyl-5-phosphonates from azides, alkynes, and H-phosphates.

    Science.gov (United States)

    Li, Lingjun; Hao, Guoliang; Zhu, Anlian; Fan, Xincui; Zhang, Guisheng; Zhang, Lihe

    2013-10-18

    Three is better than one! A new copper-catalyzed tricomponent reaction of a terminal alkyne, organic azide, and H-phosphate (CuAA[P]C) leads to a structurally diverse polysubstituted 1,2,3-triazolyl-5-phosphonate, which provides an efficient tool for the direct introduction of phosphonic acid groups by a "click reaction". Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Reactivity and Chemoselectivity of Allenes in Rh(I)-Catalyzed Intermolecular (5 + 2) Cycloadditions with Vinylcyclopropanes: Allene-Mediated Rhodacycle Formation Can Poison Rh(I)-Catalyzed Cycloadditions

    Science.gov (United States)

    2015-01-01

    Allenes are important 2π building blocks in organic synthesis and engage as 2-carbon components in many metal-catalyzed reactions. Wender and co-workers discovered that methyl substituents on the terminal allene double bond counterintuitively change the reactivities of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with vinylcyclopropanes (VCPs). More sterically encumbered allenes afford higher cycloadduct yields, and such effects are also observed in other Rh(I)-catalyzed intermolecular cycloadditions. Through density functional theory calculations (B3LYP and M06) and experiment, we explored this enigmatic reactivity and selectivity of allenes in [Rh(CO)2Cl]2-catalyzed intermolecular (5 + 2) cycloadditions with VCPs. The apparent low reactivity of terminally unsubstituted allenes is associated with a competing allene dimerization that irreversibly sequesters rhodium. With terminally substituted allenes, steric repulsion between the terminal substituents significantly increases the barrier of allene dimerization while the barrier of the (5 + 2) cycloaddition is not affected, and thus the cycloaddition prevails. Computation has also revealed the origin of chemoselectivity in (5 + 2) cycloadditions with allene-ynes. Although simple allene and acetylene have similar reaction barriers, intermolecular (5 + 2) cycloadditions of allene-ynes occur exclusively at the terminal allene double bond. The terminal double bond is more reactive due to the enhanced d−π* backdonation. At the same time, insertion of the internal double bond of an allene-yne has a higher barrier as it would break π conjugation. Substituted alkynes are more difficult to insert compared with acetylene, because of the steric repulsion from the additional substituents. This leads to the greater reactivity of the allene double bond relative to the alkynyl group in allene-ynes. PMID:25379606

  5. Cycloadditions of 2-azaallyllithium species with conjugated polyenes.

    Science.gov (United States)

    Pearson, William H; Mans, Douglas M; Kampf, Jeff W

    2004-02-20

    2-Azaallyllithium species [R(1)CH(-)N=C(X)R(2)Li(+), where R(1) and R(2) are alkyl and X = OMe] were generated by tin-lithium exchange of (2-azaallyl)stannanes and underwent [pi4s+pi2s] and [pi6s+pi4s] cycloadditions with cyclic dienes and trienes, respectively, to generate novel bridged azabicyclic compounds in a highly diastereoselective endo fashion. The periselectivity using cycloheptatriene was modest, producing a 1:1 mixture of [pi6s+pi4s] and [pi4s+pi2s] adducts. The reactions of 2-azaallyllithium species with dienes proceeded by a [pi4s+pi2s] pathway. The cycloadducts derived from cyclic 2-azaallyllithium species possess the 7-azabicyclo[2.2.1]heptane (tropane) or 8-azabicyclo[3.2.1]octane ring system and have been elaborated into cocaine-like analogues.

  6. Synthesis of heterocycles by formal cycloadditions of isocyanides.

    Science.gov (United States)

    Kruithof, Art; Ruijter, Eelco; Orru, Romano V A

    2015-03-01

    Synthetic methodology for the synthesis of heterocycles is of continuous and high interest with applications in materials, catalysis, and medicines. Multicomponent reactions are suitable tools to efficiently generate chemically diverse sets of heterocycles with sufficient structural complexity. Especially isocyanides have proven to be particularly versatile building blocks in these one-pot processes. Due to their electronic structure, isocyanides are able to act sequentially or simultaneously as a nucleophile and an electrophile. Traditionally, isocyanides are therefore frequently used in multicomponent chemistry. In the recent literature, numerous reactions have been reported that involve formal cycloadditions of isocyanides with conjugated heterodienes. This Focus Review aims at mapping this reactivity and at providing insight into the relationship between the various reported reaction partners and the observed reactivity modes.

  7. Synthesis of 2H-indazoles by the [3 + 2] cycloaddition of arynes and sydnones.

    Science.gov (United States)

    Wu, Chunrui; Fang, Yuesi; Larock, Richard C; Shi, Feng

    2010-05-21

    A rapid and efficient synthesis of 2H-indazoles has been developed, which involves the [3 + 2] dipolar cycloaddition of arynes and sydnones. The process proceeds under mild reaction conditions in good to excellent yields.

  8. 1, 3-Dipolar Cycloaddition Reaction between Vinyl Acetate and N-Alkyl Hydroxypyridinium Halide

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    1, 3 Dipolar cycloaddition reaction between vinyl acetate and 3-hydroxypyridiniun betaine was performed under solid-liquid phase transfer catalytic condition. This reaction has been successfully used on the synthesis of an analogue of Bao-Gong-Teng A.

  9. Solvent-free one-pot 1,3-dipolar cycloaddition reactions of dihydropyran derived nitrone

    Indian Academy of Sciences (India)

    Bhaskar Chakraborty; Prawin Kumar Sharma; Neelam Rai; Chiran Devi Sharma

    2012-05-01

    Microwave-induced 1,3-dipolar cycloaddition reactions of dihydropyran derived nitrone with various activated alkenes have been studied in situ and found to afford new isoxazolidine derivatives with moderate selectivity.

  10. Preparation of dispersible graphene through organic functionalization of graphene using a zwitterion intermediate cycloaddition approach

    NARCIS (Netherlands)

    Zhang, Xiaoyan; Browne, Wesley R.; Feringa, Ben L.

    2012-01-01

    Highly functionalized graphene were obtained through a zwitterion intermediate cycloaddition onto exfoliated graphene flakes under new reaction conditions. The functionalized graphene obtained formed stable dispersions in common solvents, including dimethylformamide (DMF), CHCl3 and water. Its dispe

  11. Preparation of dispersible graphene through organic functionalization of graphene using a zwitterion intermediate cycloaddition approach

    NARCIS (Netherlands)

    Zhang, Xiaoyan; Browne, Wesley R.; Feringa, Ben L.

    2012-01-01

    Highly functionalized graphene were obtained through a zwitterion intermediate cycloaddition onto exfoliated graphene flakes under new reaction conditions. The functionalized graphene obtained formed stable dispersions in common solvents, including dimethylformamide (DMF), CHCl3 and water. Its

  12. The Copper-nicotinamide complex: sustainable applications in coupling and cycloaddition reactions

    Science.gov (United States)

    Crystalline copper (II)-nicotinamide complex, synthesized via simple mixing of copper chloride and nicotinamide solution at room temperature, catalyzes the C-S, C-N bond forming and cycloaddition reactions under a variety of sustainable reaction conditions.

  13. Advanced hybrid fluoropolymers from the cycloaddition of aryl trifluorovinyl ethers

    Science.gov (United States)

    Ligon, S. Clark, Jr.

    This dissertation discusses the synthesis of aryl trifluorovinyl ethers and their cycloaddition polymerization to give perfluorocyclobutyl (PFCB) polymers. To explore the stereochemistry of these polymers, simple monomfunctional aryl trifluorovinyl ethers were dimerized and the resultant cis and trans isomers were separated. Differences in structure help to improve understanding of the amorphous nature of the bulk PFCB polymeric material. To apply this knowledge, crown ether containing perfluorocyclobutyl (PFCB) polymers were synthesized for use in lithium ion battery applications. While poor solubility has hindered further development of these materials, slight modifications to structure may provide a solution. Also described is a fluorinated aryl vinyl ether and its attempted copolymerization with chlorotrifluoroethylene. While this copolymerization did not yield the desired materials, novel semifluorinated phenol precursors have been utilized in reactions with carboxylic acids to give polyesters and most recently with phosgene like species to give polycarbonates. Next, PFCB polymers were post functionalized with fluoroalkyl tethers to improve oleophobicity and hydrophobicity without decreasing thermal stability or optical clarity. In addition, various silica nanostructures were functionalized with aryl trifluorovinyl ethers. This includes the reaction of aryl silanes to give trifluorovinyl ether functional POSS and their polymerization to provide PFCB hybrid materials. Silane coupling agents were also used to functionalize colloidal silica and fumed silica nanoparticles. These procedures allow excellent dispersion of the silica nanoparticles throughout the fluoropolymer matrix. Finally, the reaction of aryl trifluorovinyl ether with nonfluorinated alkenes and alkynes was explored. In these reactions, the fluorinated olefin adds with the hydrocarbon olefin to give semifluorinated cyclobutanes (SFCB) and with the alkyne to give semifluorinated cyclobutene. The

  14. A Concomitant Allylic Azide Rearrangement/Intramolecular Azide–Alkyne Cycloaddition Sequence

    Science.gov (United States)

    2015-01-01

    An intramolecular Huisgen cycloaddition of an interconverting set of isomeric allylic azides with alkynes affords substituted triazoles in high yield. The stereoisomeric vinyl-substituted triazoloxazines formed depend on the rate of cycloaddition of the different allylic azide precursors when the reaction is carried out under thermal conditions. In contrast, dimerized macrocyclic products were obtained when the reaction was done using copper(I)-catalyzed conditions, demonstrating the ability to control the reaction products through changing conditions. PMID:24635056

  15. Theoretical studies of excited state 1,3 dipolar cycloadditions

    Science.gov (United States)

    Belluccci, Michael A.

    The 1,3 dipolar photocycloaddition reaction between 3-hydroxy-4',5,7-trimethoxyflavone (3-HTMF) and methyl cinnamate is investigated in this work. Since its inception in 2004 [JACS, 124, 13260 (2004)], this reaction remains at the forefront in the synthetic design of the rocaglamide natural products. The reaction is multi-faceted in that it involves multiple excited states and is contingent upon excited state intramolecular proton transfer (ESIPT) in 3-HTMF. Given the complexity of the reaction, there remain many questions regarding the underlying mechanism. Consequently, throughout this work we investigate the mechanism of the reaction along with a number of other properties that directly influence it. To investigate the photocycloaddition reaction, we began by studying the effects of different solvent environments on the ESIPT reaction in 3-hydroxyflavone since this underlying reaction is sensitive to the solvent environment and directly influences the cycloaddition. To study the ESIPT reaction, we developed a parallel multi-level genetic program to fit accurate empirical valence bond (EVB) potentials to ab initio data. We found that simulations with our EVB potentials accurately reproduced experimentally determined reaction rates, fluorescence spectra, and vibrational frequency spectra in all solvents. Furthermore, we found that the ultrafast ESIPT process results from a combination of ballistic transfer and intramolecular vibrational redistribution. To investigate the cycloaddition reaction mechanism, we utilized the string method to obtain minimum energy paths on the ab initio potential. These calculations demonstrated that the reaction can proceed through formation of an exciplex in the S1 state, followed by a non-adiabatic transition to the ground state. In addition, we investigated the enantioselective catalysis of the reaction using alpha,alpha,alpha',alpha'-tetraaryl-1,3-dioxolan-4,5-dimethanol alcohol (TADDOL). We found that TADDOL lowered the energy

  16. Coordinatively unsaturated ruthenium complexes as efficient alkyneazide cycloaddition catalysts

    KAUST Repository

    Lamberti, Marina

    2012-01-23

    The performance of 16-electron ruthenium complexes with the general formula Cp*Ru(L)X (in which L = phosphine or N-heterocyclic carbene ligand; X = Cl or OCH2CF3) was explored in azidealkyne cycloaddition reactions that afford the 1,2,3- triazole products. The scope of the Cp*Ru(PiPr 3)Cl precatalyst was investigated for terminal alkynes leading to new 1,5-disubstituted 1,2,3-triazoles in high yields. Mechanistic studies were conducted and revealed a number of proposed intermediates. Cp*Ru- (PiPr3)(2-HCCPh)Cl was observed and characterized by 1H, 13C, and 31P NMR at temperatures between 273 and 213 K. A rare example of N,N-κ2-phosphazide complex, Cp*Ru(κ2- iPr3PN3Bn)Cl, was fully characterized, and a single-crystal X-ray diffraction structure was obtained. DFT calculations describe a complete map of the catalytic reactivity with phenylacetylene and/or benzylazide. © 2012 American Chemical Society.

  17. Chemical functionalization of graphene via aryne cycloaddition: a theoretical study.

    Science.gov (United States)

    Zhao, Jing-xiang; Wang, Hong-xia; Gao, Bo; Wang, Xiao-guang; Cai, Qing-hai; Wang, Xuan-zhang

    2012-06-01

    Chemical functionalization of graphene provides a promising route to improve its solubility in water and organic solvents as well as modify its electronic properties, thus significantly expanding its potential applications. In this article, by using density functional theory (DFT) methods, we have studied the effects of the chemical functionalization of graphenes via aryne cycloaddition on its properties. We found that the adsorption of an isolated aryne group on the graphene sheet is very weak with the adsorption energy of -0.204 eV, even though two new single C-C interactions are formed between the aryne group and the graphene. However, the interaction of graphene with the aryne group can be greatly strengthened by (i) substituting the H-atoms in aryne group with F-, Cl-, -NO(2) (electron-withdrawing capability), or CH(3)-group (electron-donating capability), and (ii) increasing the coverage of the adsorbed aryne groups on the graphene sheet. As expected, the strongest bonding is found on the graphene edges, in which the adsorbed aryne groups prefer to be far away from each other. Interestingly, chemical functionalization with aryne groups leads to an opening of the band gap of graphene, which is dependent on the coverage of the adsorbed aryne groups. The present work provides an insight into the modifications of graphene with aryne groups in experiment.

  18. One-step ligand exchange reaction as an efficient way for functionalization of magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mrowczynski, Radoslaw [Humboldt-University Berlin, Department of Chemistry (Germany); Rednic, Lidia; Turcu, Rodica [National Institute of Research and Development for Isotopic and Molecular Technologies (Romania); Liebscher, Juergen, E-mail: liebscher@chemie.hu-berlin.de [Humboldt-University Berlin, Department of Chemistry (Germany)

    2012-07-15

    Novel magnetic Fe{sub 3}O{sub 4} nanoparticles (NPs) covered by one layer of functionalized fatty acids, bearing entities (Hayashi catalyst, biotin, quinine, proline, and galactose) of high interest for practical application in nanomedicine or organocatalysis, were synthesized. The functionalized fatty acids were obtained by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) of azido fatty acids with alkynes. All the magnetic NPs show superparamagnetic behavior with high values of magnetization and high colloidal stability in DCM solution.

  19. Novel peptide-based protease inhibitors

    DEFF Research Database (Denmark)

    Roodbeen, Renée

    , the disulfide bridge was replaced with amide bonds of various lengths. The novel peptides did not retain their inhibitory activity, but formed the basis for another strategy. Second, bicyclic peptides were obtained by creating head-to-tail cyclized peptides that were made bicyclic by the addition of a covalent...... increased. Finally, the effect of multivalent display of upain-2 was investigated. Several dimers of upain-2 were made and the attachment of upain-2 via the Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) onto an alkyne functionalized carbohydrate scaffold was investigated. Besides the synthesis...

  20. Silica-based 2-(N,N-dimethylamino)-1,3-propanediol hydrophilic interaction liquid chromatography stationary phase for separating cephalosporins and carbapenems.

    Science.gov (United States)

    Yin, Wei; Cheng, Lingping; Chai, Huihui; Guo, Ruiqiang; Liu, Renhua; Chu, Changhu; Palasota, John A; Cai, Xiaohui

    2015-08-01

    A silica-based stationary phase bearing both hydrophilic hydroxyl and amino groups was developed by covalently bonding a small molecular N,N-dimethylamino 1,3-propanediol moiety onto silica beads via copper(I)-catalyzed Huisgen azide-alkyne 1,3-dipolar cycloaddition (CuAAC). This new stationary phase showed good HILIC characteristics and high column efficiency (the theoretical plate number is up to 37000 plates m(-1) in the case of inosine) in the separation of polar compounds, such as nucleosides and bases, organic acids, cephalosporins, and carbapenems.

  1. Click chemistry decoration of amino sterols as promising strategy to developed new leishmanicidal drugs.

    Science.gov (United States)

    Porta, Exequiel O J; Carvalho, Paulo B; Avery, Mitchell A; Tekwani, Babu L; Labadie, Guillermo R

    2014-01-01

    A series of 1,2,3-triazolylsterols was prepared from pregnenolone through reductive amination and copper(I)-catalyzed azide-alkyne cycloaddition (click chemistry). The newly generated stereocenter of the key propargylamino intermediate provided a mixture of diastereomers which were separated chromatographically, and the configuration of the R isomer was determined by X-ray crystallography. Ten triazolyl sterols were prepared, and the products and intermediates were screened in vitro against different parasites, with some compounds presenting IC50 values in the low micromolar range against Leishmania donovani. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Facile preparation of cobaltocenium-containing polyelectrolyte via click chemistry and RAFT polymerization.

    Science.gov (United States)

    Yan, Yi; Zhang, Jiuyang; Qiao, Yali; Tang, Chuanbing

    2014-01-01

    A facile method to prepare cationic cobaltocenium-containing polyelectrolyte is reported. Cobaltocenium monomer with methacrylate is synthesized by copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between 2-azidoethyl methacrylate and ethynylcobaltocenium hexafluorophosphate. Further controlled polymerization is achieved by reversible addition-fragmentation chain transfer polymerization (RAFT) by using cumyl dithiobenzoate (CDB) as a chain transfer agent. Kinetic study demonstrates the controlled/living process of polymerization. The obtained side-chain cobaltocenium-containing polymer is a metal-containing polyelectrolyte that shows characteristic redox behavior of cobaltocenium. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Update: An efficient synthesis of poly(ethylene glycol)-supported iron(II) porphyrin using a click reaction and its application for the catalytic olefination of aldehydes

    KAUST Repository

    Chinnusamy, Tamilselvi R.

    2012-05-09

    The facile synthesis of polyethylene glycol (PEG)-immobilized iron(II) porphyrin using a copper-catalyzed azide-alkyne [3+2] cycloaddition "click" reaction is reported. The prepared complex 5 (PEG-C 51H 39FeN 7O) was found to be an efficient catalyst for the selective olefination of aldehydes with ethyl diazoacetate in the presence of triphenylphosphine, and afforded excellent olefin yields with high (E) selectivities. The PEG-supported catalyst 5 was readily recovered by precipitation and filtration, and was recycled through ten runs without significant activity loss. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Clickable Polymeric Coating for Oriented Peptide Immobilization.

    Science.gov (United States)

    Sola, Laura; Gori, Alessandro; Cretich, Marina; Finetti, Chiara; Zilio, Caterina; Chiari, Marcella

    2016-01-01

    A new methodology for the fabrication of an high-performance peptide microarray is reported, combining the higher sensitivity of a layered Si-SiO2 substrate with the oriented immobilization of peptides using a N,N-dimethylacrylamide-based polymeric coating that contains alkyne monomers as functional groups. This clickable polymer allows the oriented attachment of azido-modified peptides via a copper-mediated azide/alkyne cycloaddition. A similar coating that does not contain the alkyne functionality has been used as comparison, to demonstrate the importance of a proper orientation for facilitating the probe recognition and interaction with the target antibody.

  5. 2'-Alkynylnucleotides: A Sequence- and Spin Label-Flexible Strategy for EPR Spectroscopy in DNA.

    Science.gov (United States)

    Haugland, Marius M; El-Sagheer, Afaf H; Porter, Rachel J; Peña, Javier; Brown, Tom; Anderson, Edward A; Lovett, Janet E

    2016-07-27

    Electron paramagnetic resonance (EPR) spectroscopy is a powerful method to elucidate molecular structure through the measurement of distances between conformationally well-defined spin labels. Here we report a sequence-flexible approach to the synthesis of double spin-labeled DNA duplexes, where 2'-alkynylnucleosides are incorporated at terminal and internal positions on complementary strands. Post-DNA synthesis copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions with a variety of spin labels enable the use of double electron-electron resonance experiments to measure a number of distances on the duplex, affording a high level of detailed structural information.

  6. Click on silica: systematic immobilization of Co(II) Schiff bases to the mesoporous silica via click reaction and their catalytic activity for aerobic oxidation of alcohols.

    Science.gov (United States)

    Rana, Bharat S; Jain, Suman L; Singh, Bhawan; Bhaumik, Asim; Sain, Bir; Sinha, Anil K

    2010-09-07

    The systematic immobilization of cobalt(II) Schiff base complexes on SBA-15 mesoporous silica via copper catalyzed [3 + 2] azide-alkyne cycloaddition (CuAAC) "click reaction" involving either step-wise synthesis of silica-bound Schiff base ligand followed by its subsequent complexation with cobalt ions, or by the direct immobilization of preformed Co(II) Schiff base complex to the silica support is described. The catalytic activity of the prepared complexes was studied for the oxidation of alcohols to carbonyl compounds using molecular oxygen as oxidant. The immobilized complexes were recycled for several runs without loss in catalytic activity and no leaching was observed during this course.

  7. In situ activity-based protein profiling of serine hydrolases in E. coli

    Directory of Open Access Journals (Sweden)

    Dmitry Shamshurin

    2014-09-01

    Full Text Available A fluorophosphonate based alkyne activity probe was used for the selective labeling of active serine hydrolases in intact Escherichia coli cells. A biotin-azide tag was subsequently attached to the alkyne functionality of the probe with copper-catalyzed azide-alkyne cycloaddition (CuAAC reaction. Comparison of proteins from in-cell and lysate labeled preparations suggested qualitatively similar patterns of reactivity in both preparations. Approximately 68%, 30 of the total 44 serine hydrolases detectable in E. coli were labeled with the probe indicating significant coverage with a single probe. The methods described here offer a useful tool for profiling and monitoring serine hydrolase activity in situ.

  8. Fast, Cell-compatible Click Chemistry with Copper-chelating Azides for Biomolecular Labeling**

    Science.gov (United States)

    Uttamapinant, Chayasith; Tangpeerachaikul, Anupong; Grecian, Scott; Clarke, Scott; Singh, Upinder; Slade, Peter; Gee, Kyle R.; Ting, Alice. Y.

    2012-01-01

    We report that azides capable of copper-chelation undergo much faster “Click chemistry” (copper-accelerated azide-alkyne cycloaddition, or CuAAC) than nonchelating azides under a variety of biocompatible conditions. This kinetic enhancement allowed us to perform site-specific protein labeling on the surface of living cells with only 10–40 µM CuI/II and much higher signal than could be obtained using the best previously-reported live-cell compatible CuAAC labeling conditions. Detection sensitivity was also increased for CuAAC detection of alkyne-modified proteins and RNA labeled by metabolic feeding. PMID:22555882

  9. Selective posttranslational modification of phage-displayed polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Tsao, Meng-Lin; Tian, Feng; Schultz, Peter

    2013-02-05

    The invention relates to posttranslational modification of phage-displayed polypeptides. These displayed polypeptides comprise at least one unnatural amino acid, e.g., an aryl-azide amino acid such as p-azido-L-phenylalanine, or an alkynyl-amino acid such as para-propargyloxyphenylalanine, which are incorporated into the phage-displayed fusion polypeptide at a selected position by using an in vivo orthogonal translation system comprising a suitable orthogonal aminoacyl-tRNA synthetase and a suitable orthogonal tRNA species. These unnatural amino acids advantageously provide targets for posttranslational modifications such as azide-alkyne [3+2]cycloaddition reactions and Staudinger modifications.

  10. Selective posttranslational modification of phage-displayed polypeptides

    Energy Technology Data Exchange (ETDEWEB)

    Tsao, Meng-Lin; Tian, Feng; Schultz, Peter

    2013-11-19

    The invention relates to posttranslational modification of phage-displayed polypeptides. These displayed polypeptides comprise at least one unnatural amino acid, e.g., an aryl-azide amino acid such as p-azido-L-phenylalanine, or an alkynyl-amino acid such as para-propargyloxyphenylalanine, which are incorporated into the phage-displayed fusion polypeptide at a selected position by using an in vivo orthogonal translation system comprising a suitable orthogonal aminoacyl-tRNA synthetase and a suitable orthogonal tRNA species. These unnatural amino acids advantageously provide targets for posttranslational modifications such as azide-alkyne [3+2] cycloaddition reactions and Staudinger modifications.

  11. Azidopropylvinylsulfonamide as a New Bifunctional Click Reagent for Bioorthogonal Conjugations: Application for DNA-Protein Cross-Linking.

    Science.gov (United States)

    Dadová, Jitka; Vrábel, Milan; Adámik, Matej; Brázdová, Marie; Pohl, Radek; Fojta, Miroslav; Hocek, Michal

    2015-11-01

    N-(3-Azidopropyl)vinylsulfonamide was developed as a new bifunctional bioconjugation reagent suitable for the cross-linking of biomolecules through copper(I)-catalyzed azide-alkyne cycloaddition and thiol Michael addition reactions under biorthogonal conditions. The reagent is easily clicked to an acetylene-containing DNA or protein and then reacts with cysteine-containing peptides or proteins to form covalent cross-links. Several examples of bioconjugations of ethynyl- or octadiynyl-modified DNA with peptides, p53 protein, or alkyne-modified human carbonic anhydrase with peptides are given.

  12. One-pot synthesis of Au@SiO2 catalysts: A click chemistry approach

    KAUST Repository

    Solovyeva, Vera A.

    2014-10-13

    Using the copper-catalyzed azide-alkyne cycloaddition "click" reaction, a library of triazole amphiphiles with a variety of functional polar "heads" and hydrophobic or superhydrophobic "tails" was synthesized. The amphiphiles were evaluated for their ability to stabilize small Au nanoparticles, and, at the same time, serve as templates for nanocasting porous SiO2. One of the Au@SiO2 materials thus prepared was found to be a highly active catalyst for the Au nanoparticle-catalyzed regioselective hydroamination of alkynes.

  13. Synthesis of Donor-Acceptor Conjugated Polymers by "CLICK" Polymerization for OPV applications

    DEFF Research Database (Denmark)

    Brandt, Rasmus Guldbæk; Yu, Donghong

    The intent of this study was to utilize the Copper(I)-catalyzed Azide Alkyne Cycloaddition (CuAAC) as a polymerization technique (“Click” Polymerization) for synthesizing novel π-conjugated low band gap polymers for organic photovoltaic applications (OPV). The chosen approach was to synthesize...... an alternating electron donating (donor, D) and electron withdrawing (acceptor, A) co-polymer. The chosen monomers were well known units, and the novelty lies in using the monomer units with the click methodology. An insoluble alternating copolymer consisting of 2,7-diazido-9,9-dioctyl-9Hflourene and 1...

  14. Pyrene-Based Small Molecular Nonlinear Optical Materials Modified by ``Click-Reaction''

    Science.gov (United States)

    Liang, Pengxia; Li, Zhengqiang; Mi, Yongsheng; Yang, Zhou; Wang, Dong; Cao, Hui; He, Wanli; Yang, Huai

    2015-08-01

    Two pyrene derivatives were successfully synthesized via an efficient copper(I)-catalyzed azide alkyne 1,3-dipolar cycloaddition. The photophysical and electrochemical properties were characterized using ultraviolet-visible absorption spectra, fluorescence spectra, cyclic voltammograms and density functional theory modulations. These results showed that the symmetry structure of these derivatives formed an electron-delocalized organic system, which have larger effects in achieving a third-order nonlinear optical (NLO) response. The third-order nonlinear properties including the nonlinear absorption and the nonlinear susceptibilities investigated by Z-scan technique indicate that the title compounds can serve as a promising candidate for third-order NLO applications.

  15. CuAAC: An Efficient Click Chemistry Reaction on Solid Phase.

    Science.gov (United States)

    Castro, Vida; Rodríguez, Hortensia; Albericio, Fernando

    2016-01-11

    Click chemistry is an approach that uses efficient and reliable reactions, such as Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC), to bind two molecular building blocks. CuAAC has broad applications in medicinal chemistry and other fields of chemistry. This review describes the general features and applications of CuAAC in solid-phase synthesis (CuAAC-SP), highlighting the suitability of this kind of reaction for peptides, nucleotides, small molecules, supramolecular structures, and polymers, among others. This versatile reaction is expected to become pivotal for meeting future challenges in solid-phase chemistry.

  16. 1,3-Dipolar Cycloadditions of Benzonitrile Oxide with Various Dipolarophiles in Aqueous Solutions. A Kinetic Study

    NARCIS (Netherlands)

    Mersbergen, Dick van; Wijnen, Jan W.; Engberts, Jan B.F.N.

    1998-01-01

    The second-order rate constants for the 1,3-dipolar cycloaddition of benzonitrile oxide (1) with various dipolarophiles (2a-e) were determined in aqueous media and in organic solvents to gain more insight into the influence of an aqueous medium on pericyclic reactions. 1,3-Dipolar cycloadditions wit

  17. Dimerization of propargyl and homopropargyl 6-azido-6-deoxy-glycosides upon 1,3-dipolar cycloaddition

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Copper-catalyzed, thermal or microwave promoted 1,3-dipolar cycloaddition (Click Reaction of 2-propynyl and 3-butynyl 2,3,4-tri-O-acetyl-6-azido-6-deoxy-glycopyranosides in the D-gluco, D-galacto and D-manno series afford the corresponding dimeric cycloaddition products.

  18. Application of cycloaddition reactions to the syntheses of novel boron compounds.

    Science.gov (United States)

    Zhu, Yinghuai; Siwei, Xiao; Maguire, John A; Hosmane, Narayan S

    2010-12-21

    This review covers the application of cycloaddition reactions in forming the boron-containing compounds such as symmetric star-shaped boron-enriched dendritic molecules, nano-structured boron materials and aromatic boronic esters. The resulting boron compounds are potentially important reagents for both materials science and medical applications such as in boron neutron capture therapy (BNCT) in cancer treatment and as drug delivery agents and synthetic intermediates for carbon-carbon cross-coupling reactions. In addition, the use of boron cage compounds in a number of cycloaddition reactions to synthesize unique aromatic species will be reviewed briefly.

  19. Application of Cycloaddition Reactions to the Syntheses of Novel Boron Compounds

    Directory of Open Access Journals (Sweden)

    John A. Maguire

    2010-12-01

    Full Text Available This review covers the application of cycloaddition reactions in forming the boron-containing compounds such as symmetric star-shaped boron-enriched dendritic molecules, nano-structured boron materials and aromatic boronic esters. The resulting boron compounds are potentially important reagents for both materials science and medical applications such as in boron neutron capture therapy (BNCT in cancer treatment and as drug delivery agents and synthetic intermediates for carbon-carbon cross-coupling reactions. In addition, the use of boron cage compounds in a number of cycloaddition reactions to synthesize unique aromatic species will be reviewed briefly.

  20. [2+2+2] Cycloaddition Reactions of Macrocyclic Systems Catalyzed by Transition Metals. A Review

    Directory of Open Access Journals (Sweden)

    Anna Roglans

    2010-12-01

    Full Text Available Polyalkyne and enediyne azamacrocycles are prepared from arenesulfonamides and various alkyne and alkene derivatives either under basic or neutral conditions. The new family of macrocyclic substrates is tested in the [2+2+2] cycloaddition reaction. Several catalysts are used for the cycloisomerization reaction, and their enantioinduction is evaluated as appropriate. The effect of the structural features of the macrocycles, namely the ring size, substituents in precise positions and the number and type of unsaturations, on the [2+2+2] cycloaddition reaction has also been studied.

  1. Development of chiral metal amides as highly reactive catalysts for asymmetric [3 + 2] cycloadditions

    Science.gov (United States)

    Yamashita, Yasuhiro; Yoshimoto, Susumu; Dutton, Mark J

    2016-01-01

    Summary Highly efficient catalytic asymmetric [3 + 2] cycloadditions using a chiral copper amide are reported. Compared with the chiral CuOTf/Et3N system, the CuHMDS system showed higher reactivity, and the desired reactions proceeded in high yields and high selectivities with catalyst loadings as low as 0.01 mol %. PMID:27559396

  2. A Palladium-Catalyzed Vinylcyclopropane (3 + 2) Cycloaddition Approach to the Melodinus Alkaloids

    KAUST Repository

    Goldberg, Alexander F. G.

    2011-08-19

    A palladium-catalyzed (3+2) cycloaddition of a vinylcyclopropane and a β-nitrostyrene is employed to rapidly assemble the cyclopentane core of the Melodinus alkaloids. The ABCD ring system of the natural product family is prepared in six steps from commercially available materials.

  3. Cycloadditions to Epoxides Catalyzed by GroupIII-V Transition-Metal Complexes

    KAUST Repository

    D'Elia, Valerio

    2015-05-25

    Complexes of groupIII-V transition metals are gaining increasing importance as Lewis acid catalysts for the cycloaddition of dipolarophiles to epoxides. This review examines the latest reports, including homogeneous and heterogeneous applications. The pivotal step for the cycloaddition reactions is the ring opening of the epoxide following activation by the Lewis acid. Two modes of cleavage (C-C versus C-O) have been identified depending primarily on the substitution pattern of the epoxide, with lesser influence observed from the Lewis acid employed. The widely studied cycloaddition of CO2 to epoxides to afford cyclic carbonates (C-O bond cleavage) has been scrutinized in terms of catalytic efficiency and reaction mechanism, showing that unsophisticated complexes of groupIII-V transition metals are excellent molecular catalysts. These metals have been incorporated, as well, in highly performing, recyclable heterogeneous catalysts. Cycloadditions to epoxides with other dipolarophiles (alkynes, imines, indoles) have been conducted with scandium triflate with remarkable performances (C-C bond cleavage). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. TfOH-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1-diesters with nitriles.

    Science.gov (United States)

    Cui, Bo; Ren, Jun; Wang, Zhongwen

    2014-01-17

    A triflic acid-catalyzed formal [3 + 2] cycloaddition of cyclopropane 1,1-diesters with nitriles was developed. This reaction was expeditious, and the scope of the substituents in both cyclopropanes and nitriles was broad. This supplies an efficient and practical method for the synthesis of 1-pyrrolines.

  5. Total synthesis of (+/-)-strychnine via a [4 + 2]-cycloaddition/rearrangement cascade.

    Science.gov (United States)

    Zhang, Hongjun; Boonsombat, Jutatip; Padwa, Albert

    2007-01-18

    A new strategy for the synthesis of the Strychnos alkaloid (+/-)-strychnine has been developed and is based on an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran. The critical D-ring was assembled by an intramolecular palladium-catalyzed enolate-driven cross-coupling of an N-tethered vinyl iodide. [reaction: see text].

  6. Pseudo-bimolecular [2+2] cycloaddition studied by time-resolved photoelectron spectroscopy

    DEFF Research Database (Denmark)

    Brogaard, Rasmus Y; Boguslavskiy, Andrey E; Schalk, Oliver

    2011-01-01

    The first study of pseudo-bimolecular cycloaddition reaction dynamics in the gas phase is presented. We used femtosecond time-resolved photoelectron spectroscopy (TRPES) to study the [2+2] photocycloaddition in the model system pseudo-gem-divinyl[2.2]paracyclophane. From X-ray crystal diffraction...

  7. A kinetic study of 1,3-dipolar cycloadditions in micellar media

    NARCIS (Netherlands)

    Rispens, T; Engberts, JBFN

    2003-01-01

    The kinetics of the 1,3-dipolar cycloadditions (DC) of benzonitrile oxide with a series of N-substituted maleimides in micellar media have been investigated. Surfactants studied include anionic sodium dodecyl sulfate, cationic cetyltrimethylammonium bromide, and a series of nonionic alkyl poly(ethyl

  8. One-Pot Functionalization of Graphene with Porphyrin through Cycloaddition Reactions

    NARCIS (Netherlands)

    Zhang, Xiaoyan; Hou, Lili; Cnossen, Arjen; Coleman, Anthony C.; Ivashenko, Oleksii; Rudolf, Petra; Wees, Bart J. van; Browne, Wesley R.; Feringa, Ben L.

    2011-01-01

    Two types of graphene-based hybrid materials, graphene-TPP (TPP=tetraphenylporphyrin) and graphene-PdTPP (PdTPP=palladium tetraphenylporphyrin), were prepared directly from pristine graphene through one-pot cycloaddition reactions. The hybrid materials were characterized by thermogravimetric analysi

  9. Construction of Nine-Membered Heterocycles through Palladium-Catalyzed Formal [5+4] Cycloaddition.

    Science.gov (United States)

    Yang, Li-Cheng; Rong, Zi-Qiang; Wang, Ya-Nong; Tan, Zher Yin; Wang, Min; Zhao, Yu

    2017-03-06

    The first catalytic formal [5+4] cycloaddition to prepare nine-membered heterocycles is presented. Under palladium catalysis, the reaction of N-tosyl azadienes and substituted vinylethylene carbonates (VECs) proceeds smoothly to produce benzofuran-fused heterocycles in uniformly high efficiency. Highly diastereoselective functionalization of the nine-membered heterocycles through peripheral attack is also demonstrated.

  10. Synthesis of quinolones by nickel-catalyzed cycloaddition via elimination of nitrile.

    Science.gov (United States)

    Nakai, Kenichiro; Kurahashi, Takuya; Matsubara, Seijiro

    2013-02-15

    Substituted quinolones were efficiently synthesized via the nickel-catalyzed cycloaddition of o-cyanophenylbenzamide derivatives with alkynes. The reaction involves elimination of a nitrile group by cleavage of the two independent aryl-cyano and aryl-carbonyl C-C bonds of the amides.

  11. Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethane with Imines

    Science.gov (United States)

    Trost, Barry M.; Silverman, Steven M.; Stambuli, James P.

    2008-01-01

    The transition metal catalyzed trimethylenemethane [3+2] cycloaddition provides a direct route to functionalized heterocycles. Herein, we describe a catalytic, asymmetric protocol for the reaction between 3-acetoxy-2-trimethylsilylmethyl-1-propene and various imines. The corresponding pyrrolidines were obtained in excellent yields and enantioselectivities making use of the novel phosphoramidite L10. PMID:17887679

  12. Catalytic, Enantioselective 1,3-Dipolar Cycloadditions of Nitrile Imines with Methyleneindolinones

    Science.gov (United States)

    Gerten, Anthony L.; Slade, Michael C.; Pugh, Kelsie M.

    2013-01-01

    Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with methyleneindolinones are reported. The spiro[pyrazolin[3,3′-oxindole] products are formed in good yields (up to 98%) and high enantioselectivity (up to 99% ee). PMID:24132663

  13. Bicyclic Pyrazolidinone Derivatives from Diastereoselective Catalytic [3 + 3]-Cycloaddition Reactions of Enoldiazoacetates with Azomethine Imines

    Science.gov (United States)

    Qian, Yu; Zavalij, Peter J.; Hu, Wenhao; Doyle, Michael P.

    2013-01-01

    A highly regio- and diastereoselective synthesis of bicyclic pyrazolidinone derivatives by rhodium(II) acetate catalyzed [3+3]-annulation with enoldiazoacetates and azomethine imines has been achieved in high yield. A vinylogous reaction of the metal enol carbene with the azomethine imine initiates [3 + 3]-cycloaddition, whereas reaction at the carbene center effects N-N-cleavage of the azomethine imine. PMID:23477672

  14. Sulfoxide-directed intramolecular [4 + 2] cycloadditions between 2-sulfinyl butadienes and unactivated alkynes.

    Science.gov (United States)

    Fernández de la Pradilla, Roberto; Tortosa, Mariola; Castellanos, Esther; Viso, Alma; Baile, Raquel

    2010-03-05

    Sulfinyl dienynes undergo thermal and catalyzed IMDA cycloadditions, often at room temperature, to produce cyclohexa-1,4-dienes with good yields and high selectivities. Additionally, the products preserve a synthetically useful vinyl sulfoxide functionality. The selective manipulation of the double bonds in the cycloadducts has also been examined in this work.

  15. One-Pot Functionalization of Graphene with Porphyrin through Cycloaddition Reactions

    NARCIS (Netherlands)

    Zhang, Xiaoyan; Hou, Lili; Cnossen, Arjen; Coleman, Anthony C.; Ivashenko, Oleksii; Rudolf, Petra; Wees, Bart J. van; Browne, Wesley R.; Feringa, Ben L.

    Two types of graphene-based hybrid materials, graphene-TPP (TPP=tetraphenylporphyrin) and graphene-PdTPP (PdTPP=palladium tetraphenylporphyrin), were prepared directly from pristine graphene through one-pot cycloaddition reactions. The hybrid materials were characterized by thermogravimetric

  16. Synthesis of 2H-indazoles by the [3 + 2] dipolar cycloaddition of sydnones with arynes.

    Science.gov (United States)

    Fang, Yuesi; Wu, Chunrui; Larock, Richard C; Shi, Feng

    2011-11-04

    A rapid and efficient synthesis of 2H-indazoles has been developed using a [3 + 2] dipolar cycloaddition of sydnones and arynes. A series of 2H-indazoles have been prepared in good to excellent yields using this protocol, and subsequent Pd-catalyzed coupling reactions can be applied to the halogenated products to generate a structurally diverse library of indazoles.

  17. Microwave-assisted functionalization of carbon nanohorns via [2+1] nitrenes cycloaddition.

    Science.gov (United States)

    Karousis, Nikolaos; Ichihashi, Toshinari; Yudasaka, Masako; Iijima, Sumio; Tagmatarchis, Nikos

    2011-02-07

    The microwave-assisted functionalization of carbon nanohorns (CNHs) via [2+1] nitrenes cycloaddition, providing well dispersible hybrid materials possessing aziridino-rings covalently grafted onto the graphitic network of CNHs, was accomplished, while condensation of hydroxy-functionalized CNHs with thioctic acid, furnishing an endocyclic disulfide bond extended from the aziridino-rings, allowed the stabilization of Au nanoparticles.

  18. Functionalization of diamond (100) by organic cycloaddition reactions of nitrenes: a theoretical prediction.

    Science.gov (United States)

    Xu, Yi-Jun; Zhang, Yong-Fan; Li, Jun-Qian

    2005-09-16

    [structure: see text] We predict the viability of organic cycloadditions of nitrenes onto the diamond (100) surface. This new type of surface reaction can be employed to functionalize diamond surface at low temperature, which might introduce new functionalities to the diamond surface for novel applications in a diversity of fields.

  19. 1,3-DIPOLAR CYCLOADDITION OF PHENYL AZIDE TO NORBORNENE IN AQUEOUS-SOLUTIONS

    NARCIS (Netherlands)

    Wijnen, J.W; Steiner, R.A.; Engberts, J.B.F.N.

    1995-01-01

    Second-order rate constants for the cycloaddition of phenyl azide to norbornene were determined in aqueous solutions. In organic solvents this reaction shows a very small solvent effect. In highly aqueous media, however, remarkable accelerations are observed. The solvent dependence of the rate const

  20. Kinetic solvent effects on 1,3-dipolar cycloadditions of benzonitrile oxide

    NARCIS (Netherlands)

    Rispens, T; Engberts, JBFN

    2005-01-01

    The kinetics of 1,3-dipolar cycloadditions of benzonitrile oxide with a series of N-substituted maleimides and with cyclopentene are reported for water, a wide range of organic solvents and binary solvent mixtures. The results indicate the importance of both solvent polarity and specific hydrogen-bo

  1. Cycloadditions in mixed aqueous solvents : the role of the water concentration

    NARCIS (Netherlands)

    Rispens, T; Engberts, JBFN

    2005-01-01

    We examined the kinetics of a series of cycloaddition reactions in mixtures of water with methanol, acetonitrile and poly(ethylene glycol) (MW 1000). The reactions include the Diels-Alder (DA) reaction between cyclopentadiene and N-n-butylmaleimide or acridizinium bromide, the retro-Diels-Alder (RDA

  2. Thermal and catalytic intramolecular [4+2]-cycloaddition in 2-alkenylfurans

    Energy Technology Data Exchange (ETDEWEB)

    Zubkov, Fedor I; Nikitina, Evgenia V; Varlamov, Alexey V [Department of Physical, Mathematical and Natural Sciences, Peoples' Friendship University of Russia (Russian Federation)

    2005-07-31

    The published data on the intramolecular Diels-Alder reaction in compounds of the 2-alkenylfuran series are generalised. The methods and conditions for the preparation of tricyclic systems are considered. The effects of the substituents in the furan and the unsaturated fragments on the cycloaddition are discussed. The application of this reaction to the synthesis of alkaloids and terpenoids is exemplified.

  3. Synthesis of pyrroles by consecutive multicomponent reaction/[4 + 1] cycloaddition of alpha-iminonitriles with isocyanides.

    Science.gov (United States)

    Fontaine, Patrice; Masson, Géraldine; Zhu, Jieping

    2009-04-02

    [4 + 1] Cycloaddition of alpha,beta-unsaturated imidoyl cyanide (2-cyano-1-azadienes) with isocyanides in the presence of a catalytic amount of AlCl(3) afforded polysubstituted 2-amino-5-cyanopyrroles in good to excellent yields. In combination with the IBX/TBAB-mediated oxidative Strecker reaction, this important heterocycle is readily synthesized in two steps from simple starting materials.

  4. Copper-free 'click' : 1,3-dipolar cycloaddition of azides and arynes

    NARCIS (Netherlands)

    Campbell-Verduyn, Lachlan; Elsinga, Philip H.; Mirfeizi, Leila; Dierckx, Rudi A.; Feringa, Ben L.

    2008-01-01

    Arynes formed through fluoride-promoted ortho-elimination of o-(trimethylsilyl)aryl triflates can undergo [3 + 2] cycloaddition with various azides to form substituted benzotriazoles. The rapid reaction times and mild conditions make this an attractive variation of the classical 'click' reaction of

  5. Phosphoramidite accelerated copper(I)-catalyzed [3+2] cycloadditions of azides and alkynes

    NARCIS (Netherlands)

    Campbell-Verduyn, Lachlan S.; Mirfeizi, Leila; Dierckx, Rudi A.; Elsinga, Philip H.; Feringa, Ben L.

    2009-01-01

    Monodentate phosphoramidite ligands are used to accelerate the copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and alkynes (CuAAC) rapidly yielding a wide variety of functionalized 1,4-disubstituted-1,2,3-triazoles; Cu(I) and Cu(II) salts both function as the copper source in aqueous solutio

  6. Copper-free 'click' : 1,3-dipolar cycloaddition of azides and arynes

    NARCIS (Netherlands)

    Campbell-Verduyn, Lachlan; Elsinga, Philip H.; Mirfeizi, Leila; Dierckx, Rudi A.; Feringa, Ben L.

    2008-01-01

    Arynes formed through fluoride-promoted ortho-elimination of o-(trimethylsilyl)aryl triflates can undergo [3 + 2] cycloaddition with various azides to form substituted benzotriazoles. The rapid reaction times and mild conditions make this an attractive variation of the classical 'click' reaction of

  7. Quantum Chemistry Study of Cycloaddition Pathways for the Reaction of o-Benzyne with Fullerenes and Carbon Nanotubes

    Science.gov (United States)

    Jaffe, Richard; Han, Jie; Langhoff, Stephen R. (Technical Monitor)

    1997-01-01

    Functionalization of fullerenes via the [2+2] cycloaddition reaction with o-benzyne has been demonstrated in the laboratory. In contrast, [2+4) cycloaddition products are formed when benzyne reacts with planar polycyclic aromatic hydrocarbons. Using density functional theory (DFT) calculations with Becke's hybrid functional and small contracted gaussian basis sets, we are able to reproduce these product preferences. The objective of this work is to explore the functionalization of carbon nanotubes. We have studied o-benzyne cycloaddition products with a [14,0] single-walled nanotube. We find both the [2+2] and [2+4] adducts to be stable, with the latter product being somewhat favored.

  8. Instantaneous Click Chemistry by a Copper-Containing Polymeric-Membrane-Installed Microflow Catalytic Reactor.

    Science.gov (United States)

    Yamada, Yoichi M A; Ohno, Aya; Sato, Takuma; Uozumi, Yasuhiro

    2015-11-23

    The copper(I)-catalyzed Huisgen cycloaddition (azide-alkyne cycloaddition) is an important reaction in click chemistry that ideally proceeds instantaneously. An instantaneous Huisgen cycloaddition has been developed that uses a novel catalytic dinuclear copper complex-containing polymeric membrane-installed microflow device. A polymeric membranous copper catalyst was prepared from poly(4-vinylpyridine), copper(II) sulfate, sodium chloride, and sodium ascorbate at the interface of two laminar flows inside microchannels. Elucidation of the structure by XANES, EXAFS, and elemental analysis, as well as second-order Møller-Plesset perturbation theory (MP2) calculations and density functional theory (DFT) calculations assigned the local structure near Cu as a μ-chloro dinuclear Cu(I) complex. The microflow device promotes the instantaneous click reaction of a variety of alkynes and organic azides to afford the corresponding triazoles in quantitative yield.

  9. A diastereoselective cyclic imine cycloaddition strategy to access polyhydroxylated indolizidine skeleton: concise syntheses of (+)-/(-)-lentiginosines and (-)-2-epi-steviamine.

    Science.gov (United States)

    Shao, Jia; Yang, Jin-Song

    2012-09-21

    We describe in this paper the development of a novel diastereoselective cyclic imine cycloaddition strategy to access the polyhydroxylated indolizidine skeleton and its application in the concise syntheses of (+)-/(-)-lentiginosines and (-)-2-epi-steviamine.

  10. Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

    OpenAIRE

    Narayanarao, Manjunatha; Koodlur, Lokesh; Revanasiddappa, Vijayakumar G; Gopal, Subramanya; KAMILA, Susmita

    2016-01-01

    A new series of spiropyrrolidine compounds containing indole/indazole moieties as side chains have been accomplished via a one-pot multicomponent synthesis. The method uses the 1,3-dipolar cycloaddition reaction between N-alkylvinylindole/indazole and azomethine ylides, prepared in situ from cyclic/acyclic amino acids. The 1,3-dipolar cycloaddition proceeds efficiently under thermal conditions to afford the regio- and stereospecific cyclic adducts.

  11. Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction.

    Science.gov (United States)

    Narayanarao, Manjunatha; Koodlur, Lokesh; Revanasiddappa, Vijayakumar G; Gopal, Subramanya; Kamila, Susmita

    2016-01-01

    A new series of spiropyrrolidine compounds containing indole/indazole moieties as side chains have been accomplished via a one-pot multicomponent synthesis. The method uses the 1,3-dipolar cycloaddition reaction between N-alkylvinylindole/indazole and azomethine ylides, prepared in situ from cyclic/acyclic amino acids. The 1,3-dipolar cycloaddition proceeds efficiently under thermal conditions to afford the regio- and stereospecific cyclic adducts.

  12. Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

    Directory of Open Access Journals (Sweden)

    Manjunatha Narayanarao

    2016-12-01

    Full Text Available A new series of spiropyrrolidine compounds containing indole/indazole moieties as side chains have been accomplished via a one-pot multicomponent synthesis. The method uses the 1,3-dipolar cycloaddition reaction between N-alkylvinylindole/indazole and azomethine ylides, prepared in situ from cyclic/acyclic amino acids. The 1,3-dipolar cycloaddition proceeds efficiently under thermal conditions to afford the regio- and stereospecific cyclic adducts.

  13. Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

    Science.gov (United States)

    Narayanarao, Manjunatha; Koodlur, Lokesh; Revanasiddappa, Vijayakumar G; Gopal, Subramanya

    2016-01-01

    A new series of spiropyrrolidine compounds containing indole/indazole moieties as side chains have been accomplished via a one-pot multicomponent synthesis. The method uses the 1,3-dipolar cycloaddition reaction between N-alkylvinylindole/indazole and azomethine ylides, prepared in situ from cyclic/acyclic amino acids. The 1,3-dipolar cycloaddition proceeds efficiently under thermal conditions to afford the regio- and stereospecific cyclic adducts. PMID:28144362

  14. Covalent protein-oligonucleotide conjugates by copper-free click reaction.

    Science.gov (United States)

    Khatwani, Santoshkumar L; Kang, Jun Sung; Mullen, Daniel G; Hast, Michael A; Beese, Lorena S; Distefano, Mark D; Taton, T Andrew

    2012-07-15

    Covalent protein-oligodeoxynucleotide (protein-ODN) conjugates are useful in a number of biological applications, but synthesizing discrete conjugates-where the connection between the two components is at a defined location in both the protein and the ODN-under mild conditions with significant yield can be a challenge. In this article, we demonstrate a strategy for synthesizing discrete protein-ODN conjugates using strain-promoted azide-alkyne [3+2] cycloaddition (SPAAC, a copper-free 'click' reaction). Azide-functionalized proteins, prepared by enzymatic prenylation of C-terminal CVIA tags with synthetic azidoprenyl diphosphates, were 'clicked' to ODNs that had been modified with a strained dibenzocyclooctyne (DIBO-ODN). The resulting protein-ODN conjugates were purified and characterized by size-exclusion chromatography and gel electrophoresis. We find that the yields and reaction times of the SPAAC bioconjugation reactions are comparable to those previously reported for copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) bioconjugation, but require no catalyst. The same SPAAC chemistry was used to immobilize azide-modified proteins onto surfaces, using surface-bound DIBO-ODN as a heterobifunctional linker. Cu-free click bioconjugation of proteins to ODNs is a simple and versatile alternative to Cu-catalyzed click methods.

  15. Biocompatible click chemistry enabled compartment-specific pH measurement inside E. coli.

    Science.gov (United States)

    Yang, Maiyun; Jalloh, Abubakar S; Wei, Wei; Zhao, Jing; Wu, Peng; Chen, Peng R

    2014-09-19

    Bioorthogonal reactions, especially the Cu(I)-catalysed azide-alkyne cycloaddition, have revolutionized our ability to label and manipulate biomolecules under living conditions. The cytotoxicity of Cu(I) ions, however, has hindered the application of this reaction in the internal space of living cells. By systematically surveying a panel of Cu(I)-stabilizing ligands in promoting protein labelling within the cytoplasm of Escherichia coli, we identify a highly efficient and biocompatible catalyst for intracellular modification of proteins by azide-alkyne cycloaddition. This reaction permits us to conjugate an environment-sensitive fluorophore site specifically onto HdeA, an acid-stress chaperone that adopts pH-dependent conformational changes, in both the periplasm and cytoplasm of E. coli. The resulting protein-fluorophore hybrid pH indicators enable compartment-specific pH measurement to determine the pH gradient across the E. coli cytoplasmic membrane. This construct also allows the measurement of E. coli transmembrane potential, and the determination of the proton motive force across its inner membrane under normal and acid-stress conditions.

  16. An azide-modified nucleoside for metabolic labeling of DNA.

    Science.gov (United States)

    Neef, Anne B; Luedtke, Nathan W

    2014-04-14

    Metabolic incorporation of azido nucleoside analogues into living cells can enable sensitive detection of DNA replication through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and strain-promoted azide-alkyne cycloaddition (SPAAC) "click" reactions. One major limitation to this approach is the poor chemical stability of nucleoside derivatives containing an aryl azide group. For example, 5-azido-2'-deoxyuridine (AdU) exhibits a 4 h half-life in water, and it gives little or no detectable labeling of cellular DNA. In contrast, the benzylic azide 5-(azidomethyl)-2'-deoxyuridine (AmdU) is stable in solution at 37 °C, and it gives robust labeling of cellular DNA upon addition of fluorescent alkyne derivatives. In addition to providing the first examples of metabolic incorporation into and imaging of azide groups in cellular DNA, these results highlight the general importance of assessing azide group stability in bioorthogonal chemical reporter strategies. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. [4 + 2] cycloadditions of N-alkenyl iminium ions: structurally complex heterocycles from a three-component Diels-Alder reaction sequence.

    Science.gov (United States)

    Sarkar, Nihar; Banerjee, Abhisek; Nelson, Scott G

    2008-07-23

    N-Alkenyl iminium ions serve as conduits to three-component [4 + 2] cycloaddition reactions accessing structurally and stereochemically diverse piperidine derivatives. These cationic 2-azadienes participate in endo- or exo-selective [4 + 2] cycloadditions with electron-rich and neutral alkene dienophiles to generate a tetrahydropyridinium ion as the initial cycloadduct. In situ nucleophilic addition to the cycloaddition-derived iminium ion completes the three-component coupling sequence and affords a versatile synthesis of structurally complex piperidines.

  18. Exploring two-state reactivity pathways in the cycloaddition reactions of triplet methylene.

    Science.gov (United States)

    Pérez, Patricia; Andrés, J; Safont, V S; Contreras, Renato; Tapia, O

    2005-05-12

    Spin forbidden 1,2-cycloadditions of triplet methylene to alkenes have been theoretically studied as an example of the two-state reactivity paradigm in organic chemistry. The cycloadditions of triplet methylene to ethylene and the (E)- and (Z)-2-butene isomers show spin inversion after the transition state and therefore with no effect on the reaction rate. A local analysis shows that while triplet methylene addition to alkenes leading to the formation of a biradical intermediate is driven by spin polarization, the ring closure step to yield cyclopropane is a pericyclic process. We have found that at the regions in the potential energy surface where the spin crossover is likely to occur, the spin potential in the direction of increasing spin multiplicity, mu(+)(s), tends to equalize the one in the direction of decreasing spin multiplicity, mu(-)(s). This equalization facilitates the spin transfer process driven by changes in the spin density of the system.

  19. First-principles characterization of carbon nanotubes functionalized with [2+1] cycloadditions

    Science.gov (United States)

    Lee, Young-Su; Bonini, Nicola; Marzari, Nicola

    2007-03-01

    First-principles calculations predict that [2+1] cycloadditions of carbenes or nitrenes on single-wall carbon nanotubes can induce bond cleaving between adjacent sidewall carbons, recovering in the process the sp^2 hybridization of the pristine tubes. Electrical conductance is strongly affected by the local bonding environment, and the sp^2 re-hybridization induced by cycloadditions restores the conductance of the pristine tubes even in the presence of significant chemical or structural disorder. Phonon dispersions, Born effective charges, and polarizabilities of functionalized carbon nanotubes have been also studied, to provide a link between the local bonding structure and experimental Raman and infrared spectra. Y.-S. Lee and N. Marzari, Phys. Rev. Lett. 97, 116801 (2006).

  20. Rhodium-catalyzed acyloxy migration of propargylic esters in cycloadditions, inspiration from the recent "gold rush".

    Science.gov (United States)

    Shu, Xing-Zhong; Shu, Dongxu; Schienebeck, Casi M; Tang, Weiping

    2012-12-07

    Transition metal-catalyzed acyloxy migration of propargylic esters offers versatile entries to allene and vinyl carbene intermediates for various fascinating subsequent transformations. Most π-acidic metals (e.g. gold and platinum) are capable of facilitating these acyloxy migration events. However, very few of these processes involve redox chemistry, which are well-known for most other transition metals such as rhodium. The coupling of acyloxy migration of propargylic esters with oxidative addition, migratory insertion, and reductive elimination may lead to ample new opportunities for the design of new reactions. This tutorial review summarizes recent developments in Rh-catalyzed 1,3- and 1,2-acyloxy migration of propargylic esters in a number of cycloaddition reactions. Related Au- and Pt-catalyzed cycloadditions involving acyloxy migration are also discussed.

  1. Catalysis of Heterocyclic Azadiene Cycloaddition Reactions by Solvent Hydrogen Bonding: Concise Total Synthesis of Methoxatin.

    Science.gov (United States)

    Glinkerman, Christopher M; Boger, Dale L

    2016-09-28

    Although it has been examined for decades, no general approach to catalysis of the inverse electron demand Diels-Alder reactions of heterocyclic azadienes has been introduced. Typically, additives such as Lewis acids lead to nonproductive consumption of the electron-rich dienophiles without productive activation of the electron-deficient heterocyclic azadienes. Herein, we report the first general method for catalysis of such cycloaddition reactions by using solvent hydrogen bonding of non-nucleophilic perfluoroalcohols, including hexafluoroisopropanol (HFIP) and trifluoroethanol (TFE), to activate the electron-deficient heterocyclic azadienes. Its use in promoting the cycloaddition of 1,2,3-triazine 4 with enamine 3 as the key step of a concise total synthesis of methoxatin is described.

  2. Investigation of the Pyridinium Ylide—Alkyne Cycloaddition as a Fluorogenic Coupling Reaction

    Directory of Open Access Journals (Sweden)

    Simon Bonte

    2016-03-01

    Full Text Available The cycloaddition of pyridinium ylides with alkynes was investigated under mild conditions. A series of 13 pyridinium salts was prepared by alkylation of 4-substituted pyridines. Their reactivity with propiolic ester or amide in various reaction conditions (different temperatures, solvents, added bases was studied, and 11 indolizines, with three points of structural variation, were, thus, isolated and characterized. The highest yields were obtained when electron-withdrawing groups were present on both the pyridinium ylide, generated in situ from the corresponding pyridinium salt, and the alkyne (X, Z = ester, amide, CN, carbonyl, etc.. Electron-withdrawing substituents, lowering the acid dissociation constant (pKa of the pyridinium salts, allow the cycloaddition to proceed at pH 7.5 in aqueous buffers at room temperature.

  3. The Nitrilimine–Alkene Cycloaddition Regioselectivity Rationalized by Density Functional Theory Reactivity Indices

    Directory of Open Access Journals (Sweden)

    Giorgio Molteni

    2017-01-01

    Full Text Available Conventional frontier molecular orbital theory is not able to satisfactorily explain the regioselectivity outcome of the nitrilimine–alkene cycloaddition. We considered that conceptual density functional theory (DFT could be an effective theoretical framework to rationalize the regioselectivity of the title reaction. Several nitrilimine–alkene cycloadditions were analyzed, for which we could find regioselectivity data in the literature. We computed DFT reactivity indices at the B3LYP/6-311G(2d,p//B3LYP/6-31G(d,p and employed the grand potential stabilization criterion to calculate the preferred regioisomer. Experimental and calculated regioselectivity agree in the vast majority of cases. It was concluded that predominance of a single regioisomer can be obtained by maximizing (i the chemical potential difference between nitrilimine and alkene and (ii the local softness difference between the reactive atomic sites within each reactant. Such maximization can be achieved by carefully selecting the substituents on both reactants.

  4. Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

    Science.gov (United States)

    Yamada, Mizuki; Matsumura, Mio; Uchida, Yuki; Kawahata, Masatoshi; Murata, Yuki; Kakusawa, Naoki; Yamaguchi, Kentaro

    2016-01-01

    Summary Trisubstituted 5-stibano-1H-1,2,3-triazoles were synthesized in moderate to excellent yields by the Cu-catalyzed [3 + 2] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol %) under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4-phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively. PMID:27559379

  5. Unusual Cycloadducts from the Dipolar Cycloaddition of Allenyl Perfluoroalkyl Sulfones to Nitrones

    Institute of Scientific and Technical Information of China (English)

    WANG,Xiao-Jin; LIU,Jin-Tao

    2007-01-01

    The dipolar cycloaddition reaction of allenyl perfluoroalkyl sulfones (1) to nitrones (2) was described. Unlike nonfluorine-containing allenyl sulfones, 1 reacted readily with 2 in ether at room temperature and unusual zwitterionic cycloadducts (3) were obtained in good yields due to the strong electron-withdrawing effect of perfluoroalkyl groups. The structure of 3 was characterized by spectral analyses and X-ray crystallography.

  6. Application of Cycloaddition Reactions to the Syntheses of Novel Boron Compounds

    OpenAIRE

    Maguire, John A.; Hosmane, Narayan S; Yinghuai Zhu; Xiao Siwei

    2010-01-01

    This review covers the application of cycloaddition reactions in forming the boron-containing compounds such as symmetric star-shaped boron-enriched dendritic molecules, nano-structured boron materials and aromatic boronic esters. The resulting boron compounds are potentially important reagents for both materials science and medical applications such as in boron neutron capture therapy (BNCT) in cancer treatment and as drug delivery agents and synthetic intermediates for carbon-carbon cross-c...

  7. A facile regioselective synthesis of novel spiroacenaphthene pyrroloisoquinolines through 1,3-dipolar cycloaddition reactions

    Energy Technology Data Exchange (ETDEWEB)

    Sarrafi, Yaghoub; Asghari, Asieh; Sadatshahabi, Marzieh, E-mail: ysarrafi@umz.ac.ir [Department of Organic Chemistry, Faculty of Chemistry, University of Mazandaran (Iran, Islamic Republic of); Hamzehloueian, Mahshid [Department of Chemistry, Jouybar Branch, Islamic Azad University, Jouybar (Iran, Islamic Republic of); Alimohammadi, Kamal [Department of Chemistry, Dr. Shariati Branch, University of Farhangian, Sari (Iran, Islamic Republic of)

    2013-12-01

    An efficient one-pot three-component procedure for the synthesis of novel spiroacenaphthene pyrroloisoquinolines with high regioselectivity is described. These compounds were prepared from 1,3-dipolar cycloaddition of an azomethine ylide generated from acenaphthenequinone and 1,2,3,4-tetrahydroisoquinoline via [1,5]-H shift, with chalcone and nitrostyrene derivatives as dipolarophiles. The structure and stereochemistry of the cycloadducts have been established by single crystal X-ray structure and spectroscopic techniques. (author)

  8. Regioselective One-Pot Synthesis of Triptycenes via Triple-Cycloadditions of Arynes to Ynolates.

    Science.gov (United States)

    Umezu, Satoshi; Dos Passos Gomes, Gabriel; Yoshinaga, Tatsuro; Sakae, Mikei; Matsumoto, Kenji; Iwata, Takayuki; Alabugin, Igor; Shindo, Mitsuru

    2017-01-24

    We developed the novel one-pot synthetic method of substituted triptycenes by the reaction of ynolates and arynes. This four-step process involves three cycloadditions and electrocyclic ring opening of the strained Dewar anthracene. Each of the three related but structurally distinct classes of nucleophiles (ynolate, enolate, and anthracenolate) reacts with o-benzyne in the same predictable manner controlled by chelation and negative hyperconjugation. The resulting functionalized C3 -symmetrical triptycenes hold promise in the design of functional materials.

  9. [3 + 2]-Cycloadditions of nitrile ylides after photoactivation of vinyl azides under flow conditions

    Directory of Open Access Journals (Sweden)

    Stephan Cludius-Brandt

    2013-08-01

    Full Text Available The photodenitrogenation of vinyl azides to 2H-azirines by using a photoflow reactor is reported and compared with thermal formation of 2H-azirines. Photochemically, the ring of the 2H-azirines was opened to yield the nitrile ylides, which underwent a [3 + 2]-cycloaddition with 1,3-dipolarophiles. When diisopropyl azodicarboxylate serves as the dipolarophile, 1,3,4-triazoles become directly accessible starting from the corresponding vinyl azide.

  10. Stereocontrolled cyclic nitrone cycloaddition strategy for the synthesis of pyrrolizidine and indolizidine alkaloids.

    Science.gov (United States)

    Brandi, Alberto; Cardona, Francesca; Cicchi, Stefano; Cordero, Franca M; Goti, Andrea

    2009-08-10

    The synthesis of polyhydroxylated indolizidines and pyrrolizidines belonging to the class of iminosugars, endowed with a vast and assorted biological activity, can be achieved in a straightforward manner by a general strategy consisting of a highly stereoselective 1,3-dipolar cycloaddition of polyhydroxylated pyrroline-N-oxides followed by simple transformations of the isoxazolidine adducts. The strategy allows the complete control of the relative and absolute stereochemistry of the numerous stereogenic centers decorating these compounds.

  11. Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis of dual-function technetium complexes.

    Science.gov (United States)

    Braband, Henrik; Imstepf, Sebastian; Benz, Michael; Spingler, Bernhard; Alberto, Roger

    2012-04-02

    A new concept for the synthesis of dual-functionalized technetium (Tc) compounds is presented, on the basis of the reactivity of fac-{Tc(VII)O(3)}(+) complexes. The concept combines the "classical" bifunctional chelator (BFC) approach with the new ligand centered labeling strategy of fac-{TcO(3)}(+) complexes with alkenes ((3 + 2)-cycloaddition approach). To evidence this concept, fac-{(99)TcO(3)}(+) model complexes containing functionalized 1,4,7-triazacyclononane (tacn) derivatives N-benzyl-2-(1,4,7-triazonan-1-yl)acetamide (tacn-ba) and 2,2',2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (nota·3H) were synthesized and characterized. Whereas [(99)TcO(3)(tacn-ba)](+) [2](+) can be synthesized following a established oxidation procedure starting from the Tc(V) complex [(99)TcO(glyc)(tacn-ba)](+) [1](+), a new synthetic pathway for the synthesis of [(99)TcO(3)(nota)](2-) [5](2-) had to be developed, starting from [(99)Tc(nota·3H)(CO)(3)](+) [4](+) and using sodium perborate tetrahydrate (NaBO(3)·4H(2)O) as oxidizing reagent. While [(99)TcO(3)(nota)](2-) [5](2-) is a very attractive candidate for the development of trisubstituted novel multifunctional radioprobes, (3 + 2)-cycloaddition reactions of [(99)TcO(3)(tacn-ba)](+) [2](+) with 4-vinylbenzenesulfonate (styrene-SO(3)(-)) demonstrated the suitability of monosubstituted tacn derivatives for the new mixed "BFC-(3 + 2)-cycloaddition" approach. Kinetic studies of this reaction lead to the conclusion that the alteration of the electronic structure of the nitrogen donors by, e.g., alkylation can be used to tune the rate of the (3 + 2)-cycloaddition.

  12. Intramolecular azide to alkene cycloadditions for the construction of pyrrolobenzodiazepines and azetidino-benzodiazepines.

    Science.gov (United States)

    Hemming, Karl; Chambers, Christopher S; Jamshaid, Faisal; O'Gorman, Paul A

    2014-10-17

    The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs), pyrrolo[1,2,5]benzothiadiazepines (PBTDs), and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics.

  13. Intramolecular Azide to Alkene Cycloadditions for the Construction of Pyrrolobenzodiazepines and Azetidino-Benzodiazepines

    Directory of Open Access Journals (Sweden)

    Karl Hemming

    2014-10-01

    Full Text Available The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs, pyrrolo[1,2,5]benzothiadiazepines (PBTDs, and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics.

  14. SYNTHESIS AND CHARACTERIZATION OF TRIAZOLE CONTAINING LIQUID CRYSTALLINE POLYMERS THROUGH 1,3-DIPOLAR CYCLOADDITION POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    Devamani; Srividhya; Sundaram; Manjunathan; Sivashankaran; Nithyanandan; Subramanan; Balamurugan; Sengodan; Senthil

    2009-01-01

    Liquid crystalline polymers containing 1,2,3-triazole units as linking groups have been synthesized from the monomers containing triad ester diazide and flexible dialkyne ester by 1,3-cycloaddition reaction and were characterized. Click reaction of azide and alkyne functionals catalyzed by Cu(I) yielded target polyesters with 1,2,3-triazole groups.The structure of the polymer was confirmed by spectral techniques.GPC analysis reveals that the polymers have moderate molecular weight with narrow distributio...

  15. Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyldi-p-tolylstibane with organic azides

    Directory of Open Access Journals (Sweden)

    Mizuki Yamada

    2016-06-01

    Full Text Available Trisubstituted 5-stibano-1H-1,2,3-triazoles were synthesized in moderate to excellent yields by the Cu-catalyzed [3 + 2] cycloaddition of a ethynylstibane with organic azides in the presence of CuBr (5 mol % under aerobic conditions. The reaction of 5-stibanotriazole with HCl, I2, and NOBF4 afforded 1-benzyl-4-phenyltriazole, 1-benzyl-5-iodo-4-phenyltriazole, and a pentavalent organoantimony compound, respectively.

  16. 1,3-Dipolar Cycloaddition in the Preparation of New Fused Heterocyclic Compounds via Thermal Initiation

    Directory of Open Access Journals (Sweden)

    Martin Porubský

    2016-02-01

    Full Text Available This paper describes the synthesis of precursors with a benzo[b]furan skeleton for the intramolecular 1,3-dipolar cycloaddition of azomethine ylides prepared from N-substituted 3-allyl-aminobenzo[b]furan-2-aldehydes and secondary amines derived from α-amino acid esters. Reactions were initiated by heating. The products consisted of four fused rings with three stereogenic centers. Their structure and stereochemistry were determined by NMR spectra and X-ray measurements.

  17. Rhodium-Catalyzed Linear Codimerization and Cycloaddition of Ketenes with Alkynes

    Directory of Open Access Journals (Sweden)

    Teruyuki Kondo

    2010-06-01

    Full Text Available A novel rhodium-catalyzed linear codimerization of alkyl phenyl ketenes with internal alkynes to dienones and a novel synthesis of furans by an unusual cycloaddition of diaryl ketenes with internal alkynes have been developed. These reactions proceed smoothly with the same rhodium catalyst, RhCl(PPh33, and are highly dependent on the structure and reactivity of the starting ketenes.

  18. NMR studies on 1,3-dipolar cycloaddition of nitrile oxides to norbornenes

    Energy Technology Data Exchange (ETDEWEB)

    Gucma, Miroslaw; Golebiewski, W. Marek; Krawczyk, Maria, E-mail: golebiewski@ipo.waw.pl [Institute of Industrial Organic Chemistry, Warsaw (Poland)

    2013-05-15

    The 1,3-dipolar cycloaddition reaction of nitrile oxides to norbornenes substituted with an acrylate-derived moiety was examined. Only adducts to norbornene system were formed with a good exo selectivity and complete site-selectivity. Structures of the products were elucidated by an extensive application of electrospray ionization-mass spectrometry (ESI-MS) and 2D {sup 1}H and {sup 13}C nuclear magnetic resonance (NMR). (author)

  19. Soluble Polymer-Supported Synthesis of Pyrazoles via 1,3-Dipolar Cycloaddition Strategy

    Institute of Scientific and Technical Information of China (English)

    LIN,Xu-Feng(林旭锋); WANG,Yan-Guang(王彦广); DING,Han-Feng(丁寒锋)

    2004-01-01

    Rapid parallel liquid-phase synthesis of pyrazoles has first been developed.The 1,3-dipolar cycloaddition between nitrilimines generated in situ and soluble polymer-supported alkynyl or alkenyl dipolarophiles in parallel one-pot fashion gave the corresponding PEG-supported regioisomeric pyrazoles or regiospecific pyrazolines.The latter was assuredly oxidated by DDQ to PEG-supported regiospecific pyrazoles.Cleavage from the support under mild conditions afforded pyrazoles in good yields and high purity.

  20. Iridium-catalyzed [2 + 2 + 2] cycloaddition of α,ω-diynes with nitriles.

    Science.gov (United States)

    Onodera, Gen; Shimizu, Yoshihisa; Kimura, Jun-na; Kobayashi, Junya; Ebihara, Yukiko; Kondo, Kei; Sakata, Ken; Takeuchi, Ryo

    2012-06-27

    [Ir(cod)Cl](2)/DPPF or BINAP efficiently catalyzed the cycloaddition of α,ω-diynes with nitriles to give pyridines. The reaction can accommodate a very wide range of nitriles. Both aliphatic and aromatic nitriles smoothly reacted with α,ω-diynes to give pyridines. Ten equivalents of unactivated aliphatic nitrile were enough to give the product in high yield. Aliphatic nitriles bearing an acetal or amino moiety could be used for the reaction. The highly regioselective cycloaddition of unsymmetrical diyne bearing two different internal alkyne moieties was achieved. The observed regioselectivity could be reasonably explained by considering the different reactivities of the α-position in iridacyclopentadiene. Regioselective cycloaddition was successfully applied to the synthesis of terpyridine and quinquepyridine. This chemistry was extended to a new and efficient synthesis of oligoheteroarenes. Five aromatic or heteroaromatic rings were connected in a single operation. [Ir(cod)Cl](2)/chiral diphosphine catalyst can be applied to enantioselective synthesis. Kinetic resolution of the racemic secondary benzyl nitrile catalyzed by [Ir(cod)Cl](2)/SEGPHOS gave a central carbon chiral pyridine in 80% ee. The mechanism was analyzed on the basis of the B3LYP level of density functional calculations.

  1. Theoretical study on the mechanism of cycloaddition between dimethyl methylene carbene and acetone

    Institute of Scientific and Technical Information of China (English)

    LU Xiuhui; WU Weirong; YU Haibin; XU Yuehua

    2005-01-01

    The mechanism of the cycloaddition reaction of singlet dimethyl methylene carbene and acetone has been studied by using second-order Moller-Plesset perturbation and density functional theory. The geometrical parameters, harmonic vibrational frequencies and energy of stationary points on the potential energy surface are calculated by MP2/6-31G* and B3LYP/6-31G* methods. The results show that path b of the cycloaddition reaction (1) would be the major reactive channel of the cycloaddition reaction between singlet dimethyl methylene carbene and acetone, which proceeds in two steps: i) The two reactants form an energy-rich intermediate (INT1b), which is an exothermic reaction of 23.3 kJ/mol with no energy barrier. ii) The intermediate INT1b isomerizes to a three-membered ring product (P1) via transition state TS1b with energy barrier of 22.2 kJ/mol. The reaction rate of this reaction and its competitive reactions do greatly differ, with excellent selectivity. In view of dynamics and thermodynamics, this reaction is suitable for occurring at 1 atm and temperature range of 300―800 K, in which the reaction will have not only the larger spontaneous tendency and equilibrium constant but also the faster reaction rate.

  2. A versatile pathway to end-functionalized cellulose ethers for click chemistry applications.

    Science.gov (United States)

    Kamitakahara, Hiroshi; Suhara, Ryo; Yamagami, Mao; Kawano, Haruko; Okanishi, Ryoko; Asahi, Tomoyuki; Takano, Toshiyuki

    2016-10-20

    This paper describes a versatile pathway to heterobifunctional/telechelic cellulose ethers, such as tri-O-methyl cellulosyl azide and propargyl tri-O-methyl celluloside, having one free C-4 hydroxyl group attached to the glucosyl residue at the non-reducing end for the use in Huisgen 1,3-dipolar cycloaddition and copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The one-step end-functionalization of cellulose ethers for molecular rod synthesis involves the introduction of two reactive groups at both ends of the cellulose molecule, and can afford linear triblock copolymers via CuAAC and further reactions. We were able to tailor the degree of polymerization of end-functionalized cellulose ethers with controlled amounts of a Lewis acid, namely SnCl4. Chemical structures of the above cellulose ethers and the reaction conditions for controlling molecular length are discussed.

  3. Theoretical Study of 1,3-Dipolar Cycloaddition of Hydrazoic Acid to Substituted Ynamines

    Institute of Scientific and Technical Information of China (English)

    Xiaofang Chen; Kun Yang; Keli Han

    2009-01-01

    The 1,3-dipolar cycloaddition reactions of various substituted ynamines with hydrazoic acid were theoretically investigated with the high-accuracy CBS-QB3 method. Two regioisomers,4-amine, and 5-amine substituted adducts, were obtained, with the former as the preferred yield. This regioselectivity is rationalized by the frontier molecular orbital theory. The reactivity and synchronicity are enhanced with the increase of the electron-withdrawing character of the substitute on ynamine fragment. The calculations also show that the effect of solvent increases the activation energy, and the reaction becomes even harder in polar solvent.

  4. Theoretical Study of 1,3-Dipolar Cycloaddition of Hydrazoic Acid to Substituted Ynamines

    Science.gov (United States)

    Chen, Xiao-fang; Yang, Kun; Han, Ke-li

    2009-04-01

    The 1,3-dipolar cycloaddition reactions of various substituted ynamines with hydrazoic acid were theoretically investigated with the high-accuracy CBS-QB3 method. Two regioisomers, 4-amine, and 5-amine substituted adducts, were obtained, with the former as the preferred yield. This regioselectivity is rationalized by the frontier molecular orbital theory. The reactivity and synchronicity are enhanced with the increase of the electron-withdrawing character of the substitute on ynamine fragment. The calculations also show that the effect of solvent increases the activation energy, and the reaction becomes even harder in polar solvent.

  5. Synthesis of isoxazolidines by 1,3-dipolar cycloaddition and their bioactivity

    Institute of Scientific and Technical Information of China (English)

    Cheng Chunsheng; Li Zhinian; Shu Jinyan; Li Tao; Zhang Baoyan

    2006-01-01

    A series of new isoxazolidines was prepared by 1,3-dipolar cycloaddition of different mono-substituted styrenes with 1,3-dipolar compounds that were prepared by the reaction of N-methylhydroxylamine sulfate with aromatic carbonyl substances.This synthetic pathway for the preparation of isoxazolidines was an ideal process of green chemistry.The synthetic products were 5-substituted isoxazolidines and their structures were characterized by mass and NMR (1H-,13C-,COSY,HSQC,and DEPT) spectrometry,and their bioactivity was investigated indicating that some new compounds inhibited Botrytis cinerea effectively.

  6. Synthesis and 1,3-Dipolar Cycloaddition Reactions of Chiral Maleimides

    Directory of Open Access Journals (Sweden)

    Lubor Fisera

    1997-02-01

    Full Text Available New routes to the synthesis of various novel chiral maleimides are described. The oxabicyclic anhydride 2 readily available exo-Diels-Alder adduct of furan and maleic anhydride was used as a vehicle, which in turn reacted with hydrochlorides of amino acids 3a-f in the presence of Et3N with release of furan to give the requisite novel chiral imides 4a-f in good to moderate yields. The stereoselectivity of 1,3-dipolar cycloaddition of nitrile oxides with prepared chiral imides 4a-f is investigated.

  7. Syntheses of strychnine, norfluorocurarine, dehydrodesacetylretuline, and valparicine enabled by intramolecular cycloadditions of Zincke aldehydes.

    Science.gov (United States)

    Martin, David B C; Nguyen, Lucas Q; Vanderwal, Christopher D

    2012-01-06

    A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.

  8. Synthesis of Novel Fuctionalized Glycosides Based on 1,3-Dipolar Cycloaddition

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    1 Results 1,3-Dipolar cycloaddition reaction is one of the most common methods for preparing various five membered heterocycles,and provides a conveniet protocols for constructing C-C bond with functional groups.The reaction has also been successfully used in the syntheses of C-glycosides and other sacharride derivatives.We wish to present herein our recent approaches on the synthesis of novel C-amino-glycosides,C-aminodisaccharides,spiro heterocyclic glycosides and heterocycle linked C-disaccharides,et...

  9. Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

    Directory of Open Access Journals (Sweden)

    Andreas Gansäuer

    2014-07-01

    Full Text Available An operationally simple, convenient, and mild strategy for the synthesis of triazole-substituted titanocenes via strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne has been developed. It features the first synthesis of titanocenes containing azide groups. These compounds constitute ‘second-generation’ functionalized titanocene building blocks for further synthetic elaboration. Our synthesis is modular and large numbers of the complexes can in principle be prepared in short periods of time. Some of the triazole-substituted titanocenes display high cyctotoxic activity against BJAB cells. Comparison of the most active complexes allows the identification of structural features essential for biological activity.

  10. Nitrile Oxide-Norbornene Cycloaddition as a Bioorthogonal Crosslinking Reaction for the Preparation of Hydrogels.

    Science.gov (United States)

    Truong, Vinh X; Zhou, Kun; Simon, George P; Forsythe, John S

    2015-10-01

    This communication describes the first application of cycloaddition between an in situ generated nitrile oxide with norbornene leading to a polymer crosslinking reaction for the preparation of poly(ethylene glycol) hydrogels under physiological conditions. Hydrogels with high water content and robust physical strength are readily formed within 2-5 min by a simple two-solution mixing method which allows 3D encapsulation of neuronal cells. This bioorthogonal crosslinking reaction provides a simple yet highly effective method for preparation of hydrogels to be used in bioengineering.

  11. Metal- and Protection-Free [4 + 2] Cycloadditions of Alkynes with Azadienes: Assembly of Functionalized Quinolines.

    Science.gov (United States)

    Saunthwal, Rakesh K; Patel, Monika; Verma, Akhilesh K

    2016-05-06

    A base promoted, protection-free, and regioselective synthesis of highly functionalized quinolines via [4 + 2] cycloaddition of azadienes (generated in situ from o-aminobenzyl alcohol) with internal alkynes has been discovered. The reaction tolerates a wide variety of functional groups which has been successfully extended with diynes, (2-aminopyridin-3-yl)methanol, and 1,4-bis(phenylethynyl)benzene to afford (Z)-phenyl-2-styrylquinolines, phenylnaphthyridine, and alkyne-substituted quinolines, respectively. The proposed mechanism and significant role of the solvent were well supported by isolating the azadiene intermediate and deuterium-labeling studies.

  12. 1-Azadienes in cycloaddition and multicomponent reactions towards N-heterocycles.

    Science.gov (United States)

    Groenendaal, Bas; Ruijter, Eelco; Orru, Romano V A

    2008-11-21

    1-Azadienes are versatile building blocks for the efficient construction of various N-heterocycles. Depending on the substitution pattern and reaction partner, they may participate in a range of different reactions. An overview of recent methods for the generation of 1-azadienes is presented, as well as their application in cycloaddition, electrocyclization, and multicomponent reactions. Considering the broad range of reactivities and resulting heterocyclic scaffold structures, 1-azadienes are very useful reactive intermediates for the development of modular reaction sequences in diversity-oriented synthesis.

  13. Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition.

    Science.gov (United States)

    Desbois, Nicolas; Pacquelet, Sandrine; Dubois, Adrien; Michelin, Clément; Gros, Claude P

    2015-01-01

    The Cu(I)-catalysed Huisgen cycloaddition, known as "click" reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one "cold" metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA) in MRI.

  14. Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

    Directory of Open Access Journals (Sweden)

    Nicolas Desbois

    2015-11-01

    Full Text Available The Cu(I-catalysed Huisgen cycloaddition, known as “click” reaction, has been applied to the synthesis of a range of triazole-linked porphyrin/corrole to DOTA/NOTA derivatives. Microwave irradiation significantly accelerates the reaction. The synthesis of heterobimetallic complexes was easily achieved in up to 60% isolated yield. Heterobimetallic complexes were easily prepared as potential MRI/PET (SPECT bimodal contrast agents incorporating one metal (Mn, Gd for the enhancement of contrast for MRI applications and one “cold” metal (Cu, Ga, In for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes are promising contrast agents (CA in MRI.

  15. Enantioselective Cycloaddition Reactions Catalyzed by BINOL-Derived Phosphoric Acids and N-Triflyl Phosphoramides: Recent Advances.

    Science.gov (United States)

    Held, Felix E; Grau, Dominik; Tsogoeva, Svetlana B

    2015-09-03

    Over the last several years there has been a huge increase in the development and applications of new efficient organocatalysts for enantioselective pericyclic reactions, which represent one of the most powerful types of organic transformations. Among these processes are cycloaddition reactions (e.g., [3+2]; formal [3+3]; [4+2]; vinylogous [4+2] and 1,3-dipolar cycloadditions), which belong to the most utilized reactions in organic synthesis of complex nitrogen- and oxygen-containing heterocyclic molecules. This review presents the breakthrough realized in this field using chiral BINOL-derived phosphoric acids and N-triflyl phosphoramide organocatalysts.

  16. A fluorogenic probe for the copper(I)-catalyzed azide-alkyne ligation reaction: modulation of the fluorescence emission via 3(n,pi)-1(pi,pi) inversion.

    Science.gov (United States)

    Zhou, Zhen; Fahrni, Christoph J

    2004-07-28

    Chemoselective ligation reactions represent a powerful approach for labeling of proteins or small molecules in a biological environment. We report here a fluorogenic probe that is activated by click chemistry, a highly versatile bio-orthogonal and chemoselective ligation reaction which is based on the azide moiety as the functional group. The electron-donating properties of the triazole ring that is formed in the course of the coupling reaction was effectively utilized to modulate the fluorescence output of an electronically coupled coumarin fluorophore. Under physiological conditions the probe is essentially nonfluorescent and undergoes a bright emission enhancement upon ligation with an azide. Time-resolved emission spectroscopy and semiempirical quantum-mechanical calculations suggest that the fluorescence switching is due to an inversion of the energy ordering of the emissive 1(pi,pi*) and nonemissive 3(n,pi*) excited states. The rapid kinetics of the ligation reaction render the probe attractive for a wide range of applications in biology, analytical chemistry, or material science.

  17. "Click" and Olefin Metathesis Chemistry in Water at Room Temperature Enabled by Biodegradable Micelles.

    Science.gov (United States)

    Lipshutz, Bruce H; Bošković, Zarko; Crowe, Christopher S; Davis, Victoria K; Whittemore, Hannah C; Vosburg, David A; Wenzel, Anna G

    2013-11-12

    The two laboratory reactions focus on teaching several concepts associated with green chemistry. Each uses a commercial, nontoxic, and biodegradable surfactant, TPGS-750-M, to promote organic reactions within the lipophilic cores of nanoscale micelles in water. These experiments are based on work by K. Barry Sharpless (an azide-alkyne "click" reaction) and Robert Grubbs (an olefin cross-metathesis reaction); both are suitable for an undergraduate organic laboratory. The copper-catalyzed azide-alkyne [3+2] cycloaddition of benzyl azide and 4-tolylacetylene is very rapid: the triazole product is readily isolated by filtration and is characterized by thin-layer chromatography and melting point analysis. The ruthenium-catalyzed olefin cross-metathesis reaction of benzyl acrylate with 1-hexene is readily monitored by thin-layer chromatography and gas chromatography. The metathesis experiment comparatively evaluates the efficacy of a TPGS-750-M/water medium relative to a traditional reaction performed in dichloromethane (a common solvent used for olefin metathesis).

  18. Shielding of quantum dots using diblock copolymers: implementing copper catalyzed click chemistry to fluorescent quantum dots

    Science.gov (United States)

    Merkl, Jan-Philip; Ostermann, Johannes; Schmidtke, Christian; Kloust, Hauke; Eggers, Robin; Feld, Artur; Wolter, Christopher; Kreuziger, Anna-Marlena; Flessau, Sandra; Mattoussi, Hedi; Weller, Horst

    2014-03-01

    We describe the design and optimization of an amphiphilic diblock copolymer and its use to provide surface functionalization of colloidal semiconductor nanoparticles (quantum dots, QDs). This polymer coating promotes hydrophilicity of the nanocrystals while providing numerous functional groups ideally suited for biofunctionalization of the QDs using copper-catalyzed azide alkyne Husigen 1,3-cyloaddition (i.e., cupper catalyzed "click" reaction). Copper ions are known to quench the fluorescence of QDs in solution. Thus effective shielding of the nanocrystal surface is essential to apply copper-catalyzed reactions to luminescent QDs without drastically quenching their emission. We have applied a strategy based on micellar encapsulation within poly(isoprene-block- ethylene oxide) diblock-copolymers (PI-b-PEO), where three critical factors promote and control the effectiveness of the shielding of copper ion penetration: 1) The excess of PI-b-PEO, 2) the size of PI-b-PEO and 3) insertion of an additional PS-shell grown via seeded emulsion polymerization (EP) reaction. Due to the amphiphilic character of the block-copolymer, this approach provides a shielding layer surrounding the particles, preventing metal ions from reaching the QD surfaces and maintaining high photoluminescence. The effective shielding allowed the use of copper-catalyzed azide-alkyne 1,3-cycloaddition (CuAAC) to hydrophilic and highly fluorescent QDs, opening up great possibilities for the bio functionalization of QDs.

  19. Coupling of Ligands to the Liposome Surface by Click Chemistry.

    Science.gov (United States)

    Spanedda, Maria Vittoria; De Giorgi, Marcella; Hassane, Fatouma Saïd; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

    2017-01-01

    Click chemistry represents a new bioconjugation strategy that can be used to conveniently attach various ligands to the surface of preformed liposomes. This efficient and chemoselective reaction involves a Cu(I)-catalyzed azide-alkyne cycloaddition which can be performed under mild experimental conditions in aqueous media. Here we describe the application of a model click reaction to the conjugation, in a single step, of unprotected α-1-thiomannosyl ligands, functionalized with an azide group, to liposomes containing a terminal alkyne-functionalized lipid anchor. Excellent coupling yields have been obtained in the presence of bathophenanthroline disulfonate, a water soluble copper-ion chelator, acting as a catalyst. No vesicle leakage is triggered by this conjugation reaction and the coupled mannose ligands are exposed at the surface of the liposomes. The major limitation of Cu(I)-catalyzed click reactions is that this conjugation is restricted to liposomes made of saturated (phospho)lipids. To circumvent that constraint, an example of alternative copper-free azide-alkyne click reaction has been developed. Molecular tools and results are presented here.

  20. Light-induced hetero-Diels-Alder cycloaddition: a facile and selective photoclick reaction.

    Science.gov (United States)

    Arumugam, Selvanathan; Popik, Vladimir V

    2011-04-13

    2-Napthoquinone-3-methides (oNQMs) generated by efficient photodehydration (Φ=0.2) of 3-(hydroxymethyl)-2-naphthol undergo facile hetero-Diels-Alder addition (k(D-A)∼ 4×10(4) M(-1) s(-1)) to electron-rich polarized olefins in an aqueous solution. The resulting photostable benzo[g]chromans are produced in high to quantitative yield. The unreacted oNQM is rapidly hydrated (k(H2O) ∼145 s(-1)) to regenerate the starting diol. This competition between hydration and cycloaddition makes oNQMs highly selective, since only vinyl ethers and enamines are reactive enough to form the Diels-Alder adduct in an aqueous solution; no cycloaddition was observed with other types of alkenes. To achieve photolabeling or photoligation of two substrates, one is derivatized with a vinyl ether moiety, while 3-(hydroxymethyl)-2-naphthol is attached to the other via an appropriate linker. The light-induced Diels-Alder "click" strategy permits the formation of either a permanent or hydrolytically labile linkage. Rapid kinetics of this photoclick reaction (k=4×10(4) M(-1) s(-1)) is useful for time-resolved applications. The short lifetime (τ ∼7 ms in H(2)O) of the active form of the photoclick reagent prevents its migration from the site of irradiation, thus, allowing for spatial control of the ligation or labeling.

  1. Acceleration of Enantioselective Cycloadditions Catalyzed by Second-Generation Chiral Oxazaborolidinium Triflimidates by Biscoordinating Lewis Acids.

    Science.gov (United States)

    Thirupathi, Barla; Breitler, Simon; Mahender Reddy, Karla; Corey, E J

    2016-08-31

    The activation of second-generation fluorinated oxazaborolidines by the strong acid triflimide (Tf2NH) in CH2Cl2 solution leads to highly active chiral Lewis acids that are very effective catalysts for (4 + 2) cycloaddition. We report herein that this catalytic activity can be further enhanced by the use of Tf2NH in combination with the biscoordinating Lewis acid TiCl4 or SnCl4 as a coactivator. The effective increase in acidity of an exceedingly strong protic acid is greater for biscoordinating TiCl4 and SnCl4 than for monocoordinating salts, even the strong Lewis acids AlBr3 and BBr3 in CH2Cl2 or CH2Cl2/toluene. The increase in the effective acidity of Tf2NH can be understood in terms of a stabilized cyclic anionic complex of Tf2N(-) and TiCl4, which implies a broader utility than that described here. The utility of Tf2NH-TiCl4 activation of fluorinated oxazaborolidines is documented by examples including the first enantioselective (4 + 2) cycloaddition to α,β-unsaturated acid chlorides.

  2. Stereocontrol of the Schiff Base of Substituted Benzaldehyde to Staudinger Cycloaddition Reaction

    Institute of Scientific and Technical Information of China (English)

    齐传民; 杨凌春; 孙彭利

    2003-01-01

    Syntheses of 4 novel chiral azetidin-2-one derivatives,which were characterized by 1H NMR,IR,specific rotation and elemental analysis,through Staudinger cycloaddition reaction of Schiff base of benzaldehyde with chlorine substitution at different position in benzene ring,were described.For the first time,this type of 3S,4R configuration azetidin-2-one monocrystals with many chiral centers [(3S,4R)-3-hydroxy-N-[(S)-(1-phenyl)ethyl]-4-(2''-chlorophenyl)-azetidin-2-one monocrystal]were obtained,the structures of which were determined by X-ray diffraction analysis.The effects of Schiff base of benzaldehyde with chlorine substitution at different position in benzene ring on stereoselectivity of Staudinger cycloaddition reaction products were discussed and the results are showed as below:2-chlorophenyl Schiff base favored to yield 3S,4R configuration product,but 4-chlorophenyl Schiff base favored to yield 3R,4S configuration product.The reaction orientation of 2,4-dichlorophenyl Schiff base was determined by corporate effect of 2- and 4-chlorine,and that of the 4-chlorine was more obvious.In contrast to 4-chlorophenyl,although the main product was 3R,4S configuration,3-chlorophenyl owned lower selectivity.

  3. ARTICLES: Theoretical Study on Mechanism of Cycloadditional Reaction Between Dichloro-Germylidene and Formaldehyde

    Science.gov (United States)

    Lu, Xiu-hui; Li, Yong-qing; Xu, Yue-hua; Han, Jun-feng; Shi, Le-yi

    2010-06-01

    Mechanism of the cycloadditional reaction between singlet dichloro-germylidene and formaldehyde has been investigated with MP2/6-31G* method, including geometry optimization, vibrational analysis and energies for the involved stationary points on the potential energy surface. Prom the potential energy profile, we predict that the cycloaddition reaction between singlet dichloro-germylidene and formaldehyde has two competitive dominant reaction pathways, going with the formation of two side products (INT3 and INT4), simultaneously. Both of the two competitive reactions consist of two steps, two reactants firstly form a three-membered ring intermediate INT1 and a twisted four-membered ring intermediate INT2, respectively, both of which are barrier-free exothermic reactions of 41.5 and 72.3 kJ/mol; then INT1 isomerizes to a four-membered ring product P1 via transition state TS1, and INT2 isomerizes to a chlorine-transfer product P2 via transition state TS2, with the barriers of 2.9 and 0.3 kJ/mol, respectively. Simultaneously, P1 and INT2 further react with formaldehyde to form INT3 and INT4, respectively, which are also barrier-free exothermic reaction of 74.9 and 88.1 kJ/mol.

  4. Cytotoxic conjugates of betulinic acid and substituted triazoles prepared by Huisgen Cycloaddition from 30-azidoderivatives

    Science.gov (United States)

    Sidova, Veronika; Zoufaly, Pavel; Pokorny, Jan; Dzubak, Petr; Hajduch, Marian; Popa, Igor

    2017-01-01

    In this work, we describe synthesis of conjugates of betulinic acid with substituted triazoles prepared via Huisgen 1,3-cycloaddition. All compounds contain free 28-COOH group. Allylic bromination of protected betulinic acid by NBS gave corresponding 30-bromoderivatives, their substitution with sodium azides produced 30-azidoderivatives and these azides were subjected to CuI catalysed Huisgen 1,3-cycloaddition to give the final conjugates. Reactions had moderate to high yields. All new compounds were tested for their in vitro cytotoxic activities on eight cancer and two non-cancer cell lines. The most active compounds were conjugates of 3β-O-acetylbetulinic acid and among them, conjugate with triazole substituted by benzaldehyde 9b was the best with IC50 of 3.3 μM and therapeutic index of 9.1. Five compounds in this study had IC50 below 10 μM and inhibited DNA and RNA synthesis and caused block in G0/G1 cell cycle phase which is highly similar to actinomycin D. It is unusual that here prepared 3β-O-acetates were more active than compounds with the free 3-OH group and this suggests that this set may have common mechanism of action that is different from the mechanism of action of previously known 3β-O-acetoxybetulinic acid derivatives. Benzaldehyde type conjugate 9b is the best candidate for further drug development. PMID:28158265

  5. Opioid receptor probes derived from cycloaddition of the hallucinogen natural product salvinorin A.

    Science.gov (United States)

    Lozama, Anthony; Cunningham, Christopher W; Caspers, Michael J; Douglas, Justin T; Dersch, Christina M; Rothman, Richard B; Prisinzano, Thomas E

    2011-04-25

    As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin A scaffold. This demonstrates the first reported results for both cycloaddition of the furan ring and functionalization via microwave-assisted methodology of the salvinorin A skeleton. The cycloadducts yielded herein introduce electron-withdrawing substituents and bulky aromatic groups into the C-12 position. Kappa opioid (KOP) receptor space was explored through aromatization of the bent oxanorbornadiene system possessed by the cycloadducts to a planar phenyl ring system. Although dimethyl- and diethylcarboxylate analogues 5 and 6 retain some affinity and selectivity for KOP receptors and are full agonists, their aromatized counterparts 13 and 14 have reduced affinity for KOP receptors. The methods developed herein signify a novel approach toward rapidly probing the structure-activity relationships of furan-containing natural products.

  6. Activation-strain analysis reveals unexpected origin of fast reactivity in heteroaromatic azadiene inverse-electron-demand diels-alder cycloadditions.

    Science.gov (United States)

    Talbot, Austin; Devarajan, Deepa; Gustafson, Samantha J; Fernández, Israel; Bickelhaupt, F Matthias; Ess, Daniel H

    2015-01-02

    Heteroaromatic azadienes, especially 1,2,4,5-tetrazines, are extremely reactive partners with alkenes in inverse-electron-demand Diels-Alder reactions. Azadiene cycloaddition reactions are used to construct heterocycles in synthesis and are popular as bioorthogonal reactions. The origin of fast azadiene cycloaddition reactivity is classically attributed to the inverse frontier molecular orbital (FMO) interaction between the azadiene LUMO and alkene HOMO. Here, we use a combination of ab initio, density functional theory, and activation-strain model calculations to analyze physical interactions in heteroaromatic azadiene-alkene cycloaddition transition states. We find that FMO interactions do not control reactivity because, while the inverse FMO interaction becomes more stabilizing, there is a decrease in the forward FMO interaction that is offsetting. Rather, fast cycloadditions are due to a decrease in closed-shell Pauli repulsion between cycloaddition partners. The kinetic-thermodynamic relationship found for these inverse-electron-demand cycloadditions is also due to the trend in closed-shell repulsion in the cycloadducts. Cycloaddition regioselectivity, however, is the result of differences in occupied-unoccupied orbital interactions due to orbital overlap. These results provide a new predictive model and correct physical basis for heteroaromatic azadiene reactivity and regioselectivity with alkene dieneophiles.

  7. Microwave-Enhanced Organic Syntheses for the Undergraduate Laboratory: Diels-Alder Cycloaddition, Wittig Reaction, and Williamson Ether Synthesis

    Science.gov (United States)

    Baar, Marsha R.; Falcone, Danielle; Gordon, Christopher

    2010-01-01

    Microwave heating enhanced the rate of three reactions typically performed in our undergraduate organic chemistry laboratory: a Diels-Alder cycloaddition, a Wittig salt formation, and a Williamson ether synthesis. Ninety-minute refluxes were shortened to 10 min using a laboratory-grade microwave oven. In addition, yields improved for the Wittig…

  8. Visible light-photocatalysed carbazole synthesis via a formal (4+2) cycloaddition of indole-derived bromides and alkynes.

    Science.gov (United States)

    Yuan, Zhi-Guang; Wang, Qiang; Zheng, Ang; Zhang, Kai; Lu, Liang-Qiu; Tang, Zilong; Xiao, Wen-Jing

    2016-04-14

    We successfully developed an unprecedented route to carbazole synthesis through a visible light-photocatalysed formal (4+2) cycloaddition of indole-derived bromides and alkynes. This novel protocol features extremely mild conditions, a broad substrate scope and high reaction efficiency.

  9. Synthesis of some novel fluoro isoxazolidine and isoxazoline derivatives using -benzyl fluoro nitrone via cycloaddition reaction in ionic liquid

    Indian Academy of Sciences (India)

    Bhaskar Chakraborty; Govinda Prasad Luitel

    2013-09-01

    1-Butyl-3-methylimidazolium-based ionic liquids are found to accelerate significantly the intermolecular 1,3-dipolar cycloaddition of -benzyl-fluoro nitrone derived in situ from 2,6-difluoro benzaldehyde and -benzylhydroxylamine, with activated alkenes and electron deficient alkynes to afford enhanced rates and improved yields of novel isoxazolidines and isoxazolines.

  10. Stereoselective cyclo-addition reactions of azomethine ylides catalysed by in situ generated Ag(I/bisphosphine complexes

    Directory of Open Access Journals (Sweden)

    VLADIMIR SAVIĆ

    2010-01-01

    Full Text Available Stereoselective cyclo-addition reactions of azomethine ylides promoted by in situ generated Ag(I/bisphosphine complexes were studied. Under the optimised conditions, the pyrrolidine products were isolated in up to 84 % yield and with up to 71 % e.e. The effects of various reaction variables on the stereoselectivity were also investigated.

  11. Asymmetric 1,3-Dipolar Cycloadditions to 5-(R)-Menthyloxy-2(5H)-Furanone

    NARCIS (Netherlands)

    Rispens, Minze T.; Keller, Erik; Lange, Ben de; Zijlstra, Robert W.J.; Feringa, Bernard

    Various diazo compounds, nitrile oxides, nitrones and azomethine ylides were examined in 1,3-dipolar cycloadditions to enantiomerically pure 5-(R)-menthyloxy-2(5H)-furanone 1a. Pyrazoline 9 was obtained in 100% c.y. as a mixture of 2 diastereoisomers in ratios up to 72 : 28, whereas pyrazoline 16

  12. Light-driven nitrile imine-mediated tetrazole-ene cycloaddition as a versatile platform for fullerene conjugation.

    Science.gov (United States)

    Sugawara, Yuuki; Jasinski, Nils; Kaupp, Michael; Welle, Alexander; Zydziak, Nicolas; Blasco, Eva; Barner-Kowollik, Christopher

    2015-08-21

    An efficient methodology for modular fullerene functionalization via the photo-induced nitrile imine-mediated tetrazole-ene cycloaddition (NITEC) is introduced. The versatility and platform character of the method is illustrated by the light-driven reaction of fullerenes with small molecule, polymeric and surface-immobilized tetrazoles. The efficient fullerene conjugation is evidenced via mass spectrometric techniques.

  13. Construction of the Core of Pseudolaric Acid A and Mechanistic Studies on Intramolecular [4+3] Cycloaddition

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper describes the construction of hemiacetal 2, the core of pseudolaric acid A via oxidative cleavage of acetonide 6 or 7 and enolization-hemiacetalization of aldehyde 8. A plausible general mechanism for the intramolecular [4+3] cycloaddition of sulfoxide 4 to adduct 3 is suggested.

  14. AOT-based microemulsions accelerate the 1,3-cycloaddition of benzonitrile oxide to N-ethylmaleimide

    NARCIS (Netherlands)

    Engberts, J. B. F. N.; Fernandez, E.; Garcia-Rio, L.; Leis, J. R.

    2006-01-01

    We studied the 1,3-dipolar cycloaddition of benzonitrile oxide to N-ethylmaleimide in AOT/isooctane/water microemulsions at 25.0 degrees C and found the reaction rate to be roughly 150 and 35 times greater than that in isooctane and pure water, respectively. The accelerating effect of the

  15. AOT-based microemulsions accelerate the 1,3-cycloaddition of benzonitrile oxide to N-ethylmaleimide

    NARCIS (Netherlands)

    Engberts, J. B. F. N.; Fernandez, E.; Garcia-Rio, L.; Leis, J. R.

    2006-01-01

    We studied the 1,3-dipolar cycloaddition of benzonitrile oxide to N-ethylmaleimide in AOT/isooctane/water microemulsions at 25.0 degrees C and found the reaction rate to be roughly 150 and 35 times greater than that in isooctane and pure water, respectively. The accelerating effect of the microemuls

  16. Electronic Effects versus Distortion Energies During Strain-Promoted Alkyne-Azide Cycloadditions: A Theoretical Tool to Predict Reaction Kinetics

    NARCIS (Netherlands)

    Garcia-Hartjes, J.; Dommerholt, J.; Wennekes, T.; Delft, van F.L.; Zuilhof, H.

    2013-01-01

    Second-order reaction kinetics of known strain-promoted azide–alkyne cycloaddition (SPAAC) reactions were compared with theoretical data from a range of ab initio methods. This produced both detailed insights into the factors determining the reaction rates and two straightforward theoretical tools t

  17. Fast copper-free click DNA ligation by the ring-strain promoted alkyne-azide cycloaddition reaction.

    Science.gov (United States)

    Shelbourne, Montserrat; Chen, Xiong; Brown, Tom; El-Sagheer, Afaf H

    2011-06-14

    Templated DNA strand ligation by the ring-strain promoted alkyne-azide [3+2] cycloaddition reaction is very fast; with dibenzocyclooctyne, the reaction is essentially complete in 1 min. It is inhibited by the presence of a single mismatched base pair suggesting applications in genetic analysis. This journal is © The Royal Society of Chemistry 2011

  18. Asymmetric 1,3-dipolar cycloaddition of nitrile oxides to chiral acryloyl esters bearing glucofuranose as auxiliary

    Institute of Scientific and Technical Information of China (English)

    ZHANG, Ao; KAN, Ying; JIANG, Biao

    2000-01-01

    Asymmetric 1,3-dipolar cycloaddition of nitrile oxides to an acryloyl ester (1) derived from 1,2: 5,6-di- O-isopropylidene glucose (6) was studied. Solvent and temperature effect was discussed. The single diastereoisomer was isolated with high diastereoselective excess.

  19. 1,3-Dipolar Cycloaddition of Nitrones with Electron-richAlkenes Catalyzed by Yb(OTf)3

    Institute of Scientific and Technical Information of China (English)

    QIAN, Chang-Tao; WANG, Long-Cheng; CHEN, Rui-Fang

    2001-01-01

    1,3-Dipolar cycloaddition of nitrones with ethyl vinyl ether or 2, 3-dihydrofuran proceeds smoothly in the presence of a catalytic amount (10 mol% ) of ytterbium triflate to afford isoxazolidines and dicyclic isoxazolidine respectively with good yields ahd high stereoselectivity.

  20. Protein enrichment by capture-release based on strain-promoted cycloaddition of azide with bicyclononyne (BCN).

    NARCIS (Netherlands)

    Temming, R.P.; Scherpenzeel, M. van; Brinke, E. te; Schoffelen, S.; Gloerich, J.; Lefeber, D.J.; Delft, F.L. van

    2012-01-01

    An enrichment strategy was devised for azide derivatized macromolecules, based on strain-promoted alkyne-azide cycloaddition (SPAAC) and a cleavable linker. A ring-strained alkyne, bicyclo[6.1.0]non-4-yne (BCN), was covalently attached to agarose beads via a hydrazine-sensitive linker. Benchmark

  1. Synthesis of 5-substituted 1H-tetrazoles by the copper-catalyzed [3+2] cycloaddition of nitriles and trimethylsilyl azide.

    Science.gov (United States)

    Jin, Tienan; Kitahara, Fukuzou; Kamijo, Shin; Yamamoto, Yoshinori

    2008-09-01

    The copper-catalyzed [3+2] cycloaddition between various nitriles and trimethylsilyl azide in DMF/MeOH produced the corresponding 5-substituted 1H-tetrazoles in good to high yields. It was proposed that the reaction proceeds through the formation in situ of a copper azide species and subsequent [3+2] cycloaddition with the nitriles. Furthermore, we found that a copper and triethylamine combined catalyst also promoted the cycloaddition of nitriles and trimethylsilyl azide to afford the 5-substituted 1H-tetrazoles at relatively low reaction temperatures. The copper azide species would be formed by reaction of the copper catalyst with Et(3)NHN(3) generated in situ.

  2. Functionalization of Mechanochemically Passivated Germanium Nanoparticles via "Click" Chemistry

    Science.gov (United States)

    Purkait, Tapas Kumar

    Germanium nanoparticles (Ge NPs) may be fascinating for their electronic and optoelectronic properties, as the band gap of Ge NPs can be tuned from the infrared into the visible range of solar spectru. Further functionalization of those nanoparticles may potentially lead to numerous applications ranging from surface attachment, bioimaging, drug delivery and nanoparticles based devices. Blue luminescent germanium nanoparticles were synthesized from a novel top-down mechanochemical process using high energy ball milling (HEBM) of bulk germanium. Various reactive organic molecules (such as, alkynes, nitriles, azides) were used in this process to react with fresh surface and passivate the surface through Ge-C or Ge-N bond. Various purification process, such as gel permeation chromatography (GPC), Soxhlet dailysis etc. were introduced to purify nanoparticles from molecular impurities. A size separation technique was developed using GPC. The size separated Ge NPs were characterize by TEM, small angle X-ray scattering (SAXS), UV-vis absorption and photoluminescence (PL) emission spectroscopy to investigate their size selective properties. Germanium nanoparticles with alkyne termini group were prepared by HEBM of germanium with a mixture of n-alkynes and alpha, o-diynes. Additional functionalization of those nanoparticles was achieved by copper(I) catalyzed azide-alkyne "click" reaction. A variety of organic and organometallic azides including biologically important glucals have been reacted in this manner resulting in nanopartilces adorned with ferrocenyl, trimethylsilyl, and glucal groups. Additional functionalization of those nanoparticles was achieved by reactions with various azides via a Cu(I) catalyzed azide-alkyne "click" reaction. Various azides, including PEG derivatives and cylcodextrin moiety, were grafted to the initially formed surface. Globular nanoparticle arrays were formed through interparticle linking via "click" chemistry or "host-guest" chemistry

  3. Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

    Science.gov (United States)

    Schöffler, Anne L; Makarem, Ata; Rominger, Frank

    2016-01-01

    Summary A dinuclear N-heterocyclic carbene (NHC) copper complex efficiently catalyzes azide–alkyne cycloaddition (CuAAC) “click” reactions. The ancillary ligand comprises two 4,5-dimethyl-1,3-thiazol-2-ylidene units and an ethylene linker. The three-step preparation of the complex from commercially available starting compounds is more straightforward and cost-efficient than that of the previously described 1,2,4-triazol-5-ylidene derivatives. Kinetic experiments revealed its high catalytic CuAAC activity in organic solvents at room temperature. The activity increases upon addition of acetic acid, particularly for more acidic alkyne substrates. The modular catalyst design renders possible the exchange of N-heterocyclic carbene, linker, sacrificial ligand, and counter ion. PMID:27559407

  4. Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions.

    Science.gov (United States)

    Newton, Christopher G; Drew, Samuel L; Lawrence, Andrew L; Willis, Anthony C; Paddon-Row, Michael N; Sherburn, Michael S

    2015-01-01

    The pseudopterosins are a family of diterpene marine natural products, which, by virtue of their interesting anti-inflammatory and analgesic properties, have attracted the attentions of many synthetic chemists. The most efficient syntheses reported to date are 14 and 20 steps in the longest linear sequence for chiral pool and enantioselective approaches, respectively, and all start with precursors that are easily mapped onto the natural product structure. Here, we describe an unconventional approach in which a chiral cross-conjugated hydrocarbon is used as the starting material for a series of three cycloadditions. Our approach has led to a significant reduction in the step count required to access these interesting natural products (10 steps chiral pool and 11 steps enantioselective). Furthermore it demonstrates that cross-conjugated hydrocarbons, erroneously considered by many to be too unstable and difficult to handle, are viable precursors for natural product synthesis.

  5. Functionalization of Graphene with Nitrile Groups by Cycloaddition of Tetracyanoethylene Oxide

    Directory of Open Access Journals (Sweden)

    Xiaojun Peng

    2013-01-01

    Full Text Available Graphene has got considerable attention in both experimental and theoretical fields for its extraordinary properties. Covalent functionalization is an efficient strategy to render graphene additional properties and overcome its shortcomings such as zero band gap and nondispersibility in solvents. This study reports the synthesis and characterizations of a new kind of functionalized graphene, graphene-TCNEO, obtained by 1,3-dipolar cycloaddition. The graphene-TCNEO was systematically characterized by FTIR, Raman, XPS, SEM, TEM, and EDS mapping, and the covalent linkage between graphene and tetracyanoethylene oxide was firmly verified. Considering the great diversity of nitrile chemistry, the obtained graphene-TCNEO could be further transformed into other graphene-based derivatives with interesting properties.

  6. Cycloaddition mechanism for the resin-OsO4-catalyzed of styrene: A DFT study

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The postulated intermediates in the base-free and base-assisted addition of OsO4 to styrene have been investigated at the B3LYP/6-311G** level of the theory. N(CH3)2(Ph) was chosen as the base of the resin-OsO4. According to our model calculations the [2+3] addition was found to be favorable with an activation of <45.00 Kj/mol. In contract, the reaction barriers for the [2+2] cycloaddition remain high (>155.00 Kj/mol). In addition, the electronic structure analysis of the molecules was carried out by nature bond orbital (NBO). The computational results were in reasonable agreement with experimental results.

  7. Cycloaddition mechanism for the resin-OsO4-catalyzed of styrene: A DFT study

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    The postulated intermediates in the base-free and base-assisted addition of OsO4 to styrene have been investigated at the B3LYP/6-311G** level of the theory. N(CH3)2(Ph) was chosen as the base of the resin-OsO4. According to our model calculations the [2+3] addition was found to be favorable with an activation of <45.00 kJ/mol. In contract, the reaction barriers for the [2+2] cycloaddition remain high (>155.00 kJ/mol). In addition, the electronic structure analysis of the molecules was carried out by na- ture bond orbital (NBO). The computational results were in reasonable agreement with experimental results.

  8. Bottlenecks in the prediction of regioselectivity of [4 + 2] cycloaddition reactions: An assessment of reactivity descriptors

    Indian Academy of Sciences (India)

    G Gayatri; G Narahari Sastry

    2005-09-01

    B3LYP/6-31G() calculations were performed to obtain all the transition states and products for the 128 distinct reaction channels of Diels-Alder reactions by taking all possible combinations from a series of dienes (1N-a, 1N-b, 2N, 1P-a, 1P-b, 2P, 1O, 1S) and dienophiles (NE, PE, OE, SE, AE, OHE, MeE, CNE). The predictive ability of the values to gauge the regioselectivity of the putative [4 + 2] cycloaddition reactions is analysed. No correlation is obtained between the reaction energies and activation energies. The extent of asynchronicity is measured based on the bond order analysis. DFT-based descriptors such as the local softness ($s^{+}_{k}$ and $s_{k}^{-}$), Fukui function indices ($f^{+}_{k}$ and $f_{k}^{-}$), global electrophilicity index () and local electrophilicity index () were found to be better than the conventional FMO predictions.

  9. [2+2] cycloaddition of 1,3-dienes by visible light photocatalysis.

    Science.gov (United States)

    Hurtley, Anna E; Lu, Zhan; Yoon, Tehshik P

    2014-08-18

    [2+2] photocycloadditions of 1,3-dienes represent a powerful yet synthetically underutilized class of reactions. We report that visible light absorbing transition metal complexes enable the [2+2] cycloaddition of a diverse range of 1,3-dienes. The ability to use long-wavelength visible light is attractive because these reaction conditions tolerate the presence of sensitive functional groups that might be readily decomposed by the high-energy UVC radiation required for direct photoexcitation of 1,3-dienes. The resulting vinylcyclobutane products are poised for a variety of further diversification reactions, and this method is consequently expected to be powerfully enabling in the synthesis of complex organic targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. SYNTHESIS AND CHARACTERIZATION OF TRIAZOLE CONTAINING LIQUID CRYSTALLINE POLYMERS THROUGH 1,3-DIPOLAR CYCLOADDITION POLYMERIZATION

    Institute of Scientific and Technical Information of China (English)

    Devamani Srividhya; Sundaram Manjunathan; Sivashankaran Nithyanandan; Subramanan Balamurugan; Sengodan Senthil

    2009-01-01

    Liquid crystalline polymers containing 1,2,3-triazole units as linking groups have been synthesized from the monomers containing triad ester diazide and flexible dialkyne ester by 1,3-cycloaddition reaction and were characterized. Click reaction of azide and alkyne functionals catalyzed by Cu(Ⅰ) yielded target polyesters with 1,2,3-triazole groups. The structure of the polymer was confirmed by spectral techniques. GPC analysis reveals that the polymers have moderate molecular weight with narrow distribution. Hot stage optical polarizing microscopic investigation confirms the liquid crystalline nature of the polymers with lengthy flexible spacers, while the short chain containing polymers does not show the mesomorphic properties. Differential scanning calorimetric analysis confirms the formation of mesophase in some of the polymers, and it is in accordance with the microscopic results. Thermal stabilities of the polymers were analyzed by thermogravimetric analysis.

  11. Dinuclear thiazolylidene copper complex as highly active catalyst for azid–alkyne cycloadditions

    Directory of Open Access Journals (Sweden)

    Anne L. Schöffler

    2016-07-01

    Full Text Available A dinuclear N-heterocyclic carbene (NHC copper complex efficiently catalyzes azide–alkyne cycloaddition (CuAAC “click” reactions. The ancillary ligand comprises two 4,5-dimethyl-1,3-thiazol-2-ylidene units and an ethylene linker. The three-step preparation of the complex from commercially available starting compounds is more straightforward and cost-efficient than that of the previously described 1,2,4-triazol-5-ylidene derivatives. Kinetic experiments revealed its high catalytic CuAAC activity in organic solvents at room temperature. The activity increases upon addition of acetic acid, particularly for more acidic alkyne substrates. The modular catalyst design renders possible the exchange of N-heterocyclic carbene, linker, sacrificial ligand, and counter ion.

  12. Pseudopterosin synthesis from a chiral cross-conjugated hydrocarbon through a series of cycloadditions

    Science.gov (United States)

    Newton, Christopher G.; Drew, Samuel L.; Lawrence, Andrew L.; Willis, Anthony C.; Paddon-Row, Michael N.; Sherburn, Michael S.

    2015-01-01

    The pseudopterosins are a family of diterpene marine natural products, which, by virtue of their interesting anti-inflammatory and analgesic properties, have attracted the attentions of many synthetic chemists. The most efficient syntheses reported to date are 14 and 20 steps in the longest linear sequence for chiral pool and enantioselective approaches, respectively, and all start with precursors that are easily mapped onto the natural product structure. Here, we describe an unconventional approach in which a chiral cross-conjugated hydrocarbon is used as the starting material for a series of three cycloadditions. Our approach has led to a significant reduction in the step count required to access these interesting natural products (10 steps chiral pool and 11 steps enantioselective). Furthermore it demonstrates that cross-conjugated hydrocarbons, erroneously considered by many to be too unstable and difficult to handle, are viable precursors for natural product synthesis.

  13. Solid-state polymerisation via [2+2] cycloaddition reaction involving coordination polymers.

    Science.gov (United States)

    Medishetty, Raghavender; Park, In-Hyeok; Lee, Shim Sung; Vittal, Jagadese J

    2016-03-14

    Highly crystalline metal ions containing organic polymers are potentially useful to manipulate the magnetic and optical properties to make advanced multifunctional materials. However, it is challenging to synthesise monocrystalline metal complexes of organic polymers and single-phase hybrid materials made up of both coordination and organic polymers by traditional solution crystallisation. This requires an entirely different approach in the solid-state by thermal or photo polymerisation of the ligands. Among the photochemical methods available, [2+2] cycloaddition reaction has been recently employed to generate cyclobutane based coordination polymers from the metal complexes. Cyclobutane polymers have also been integrated into coordination polymers in this way. Recent advancements in the construction of polymeric chains of cyclobutane rings through photo-dimerisation reaction in the monocrystalline solids containing metal complexes, coordination polymers and metal-organic framework structures are discussed here.

  14. Theoretical Study on the Mechanism of the Cycloaddition Reaction between Alkylidene Carbene and Ethylene

    Institute of Scientific and Technical Information of China (English)

    LU,Xiu-Hui(卢秀慧); ZHAI,Li-Min(翟利民); WU,Wei-Rong(武卫荣)

    2004-01-01

    The mechanism of cycloaddition reaction between singlet alkylidene carbene and ethylene has been investigated with second-order Moller-Plesset perturbation theory (MP2). By using 6-31G* basis , geometry optimization, vibrational analysis and energetics have been calculated for the involved stationary points on the potential energy surface. The results show that the title reaction has two major competition channels. An energy-rich intermediate (INT) is firstly formed between alkylidene carbene and ethylene through a barrier-free exothermic reaction of 63.62 kJ/mol, and the intermediate then isomerizes to a three-membered ring product (P1) and a four-memberd ring product (P2) via transition state TS1 and TS2, in which energy barriers are 47.00 and 51.02 kJ/mol, respectively. P1 is the main product.

  15. Metal-free Hydroalkoxylation-Formal [4+2] Cycloaddition Cascade for the Synthesis of Ketals.

    Science.gov (United States)

    Gharpure, Santosh J; Nanda, Santosh K; Padmaja; Shelke, Yogesh G

    2017-07-26

    A transition metal free, acid promoted cascade hydroalkoxylation-formal [4+2] cycloaddition of various alkynols with salicylaldehyde is demonstrated for the synthesis of tetrahydrofurano/pyrano-chromenes and spiroketals. In general, alkynols underwent hydroalkoxylations in an endo-dig manner when internal alkynes were used to furnish the heteroannular ketals, whereas terminal alkynes proceeded in an exo-dig fashion leading to spiroketals. The study revealed that intramolecular hydroalkoxylation of alkynols is a preferred path over a generation of oxonium ions when coupling partner is salicylaldehyde. This metal-free transformation provides a new avenue for the stereoselective synthesis of tetrahydrofurano- and pyrano-chromenes in an expeditious manner. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Rhodium-Catalyzed Acyloxy Migration of Propargylic Esters in Cycloadditions, Inspiration from Recent “Gold Rush”

    Science.gov (United States)

    Shu, Xing-Zhong; Shu, Dongxu; Schienebeck, Casi M.

    2012-01-01

    Transition metal-catalyzed acyloxy migration of propargylic esters offers versatile entries to allene and vinyl carbene intermediates for various fascinating subsequent transformations. Most π-acidic metals (e.g. gold and platinum) are capable of facilitating these acyloxy migration events. However, very few of these processes involve redox chemistry, which are well-known for most other transition metals such as rhodium. The coupling of acyloxy migration of propargylic esters with oxidative addition, migratory insertion, and reductive elimination may lead to ample new opportunities for the design of new reactions. This tutorial review summarizes recent developments in Rh-catalyzed 1,3- and 1,2-acyloxy migration of propargylic esters in a number of cycloaddition reactions. Related Au- and Pt-catalyzed cycloadditions involving acyloxy migration are also discussed. PMID:22895533

  17. Improving the tensile strength of carbon nanotube yarn via one-step double [2+1] cycloadditions

    Energy Technology Data Exchange (ETDEWEB)

    Kim, HeeJin [Kyungpook National University, Daegu (Korea, Republic of); Lee, Jaegeun; Park, Byungrak; Sa, Jeong Hoon; Jung, Alum; Kim, Teawon; Park, Junbeom; Hwang, Woonbong; Lee, Kun Hong [Pohang University of Science and Technology, Pohang (Korea, Republic of)

    2016-01-15

    The tensile strength of a CNT yarn was improved through simple one-step double [2+1] cycloaddition reactions that crosslinked the constituent CNTs using a polyethylene glycol (PEG)-diazide crosslinker. The FT-IR spectrum confirmed that the azide groups in the PEG-diazide were converted into aziridine rings, indicating that the cycloaddition reaction was successful. The generation of crosslinked CNTs was also supported by the observation of N1s peak in the XPS spectrum and the increased thermal stability of the material, as observed by TGA. The tensile strength of the CNT yarn was increased from 0.2GPa to 1.4GPa after the crosslinking reaction when twisted at 4000 twists/ meter. The appropriate selection of the crosslinker may further optimize the CNT yarn crosslinking reaction. The simplicity of this one-step crosslinking reaction provides an economical approach to the mass production of high-strength CNT yarns.

  18. Enantioselective Construction of Pyrrolidines by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition of Trimethylenemethane with Imines

    Science.gov (United States)

    Trost, Barry M.; Silverman, Steven M.

    2012-01-01

    A protocol for the enantioselective [3+2] cycloaddition of trimethylenemethane (TMM) with imines has been developed. Central to this effort were the novel phosphoramidite ligands developed in our laboratories. The conditions developed to effect an asymmetric TMM reaction using 2-trimethylsilylmethyl allyl acetate were shown to be tolerant of a wide variety of imine acceptors to provide the corresponding pyrrolidine cycloadducts with excellent yields and selectivities. Use of a bis-2-naphthyl phosphoramidite allowed the successful cycloaddition of the parent TMM with N-Boc imines, and has further permitted the reaction of substituted donors with N-tosyl aldimines and ketimines in high regio-, diastereo-, and enantioselectivity. Use of a diphenylazetidine ligand allows the complimentary synthesis of the exocyclic nitrile product shown, and we demonstrate control of the regioselectivity of the product based on manipulation of the reaction parameters. PMID:22309214

  19. A new approach to produce amino-carbon nanotubes as plasmid transfection vector by [2 + 1] cycloaddition of nitrenes

    Science.gov (United States)

    Jiang, Yongjian; Jin, Chen; Yang, Feng; Yu, Xianjun; Wang, Guojian; Cheng, Si; Di, Yang; Li, Ji; Fu, Deliang; Ni, Quanxing

    2011-01-01

    Amino-carbon nanotubes (amino-CNTs) can conjugate with the DNA by electrostatic interactions and shuttle the DNA to the cell cytoplasm or even the nucleus. Here we report a new approach to produce amino-CNTs by cycloaddition of nitrenes. Fourier transform infrared spectroscopy was used to verify the success of the functionalization, and the functionalization degree was calculated by thermal gravity analysis. Transmission electron microscope (TEM) was used to observe the solubility of the CNTs and the interactions of the amino-CNTs with the plasmids. Cell ultrathin sections were made and observed under the TEM to confirm the amino-CNTs enter the cells. Transfection experiments ultimately verify the amino-CNTs produced through cycloadditions of nitrenes can serve as plasmid vector.

  20. Growth of Fullerene Fragments Using the Diels-Alder Cycloaddition Reaction: First Step towards a C60 Synthesis by Dimerization

    Directory of Open Access Journals (Sweden)

    Julio A. Alonso

    2013-02-01

    Full Text Available Density Functional Theory has been used to model the Diels-Alder reactions of the fullerene fragments triindenetriphenilene and pentacyclopentacorannulene with ethylene and 1,3-butadiene. The purpose is to prove the feasibility of using Diels-Alder cycloaddition reactions to grow fullerene fragments step by step, and to dimerize fullerene fragments, as a way to obtain C60. The dienophile character of the fullerene fragments is dominant, and the reaction of butadiene with pentacyclopentacorannulene is favored.

  1. Remote Stereoinductive Intramolecular Nitrile Oxide Cycloaddition: Asymmetric Total Synthesis and Structure Revision of (-)-11β-Hydroxycurvularin.

    Science.gov (United States)

    Choe, Hyeonjeong; Pham, Thuy Trang; Lee, Joo Yun; Latif, Muhammad; Park, Haeil; Kang, Young Kee; Lee, Jongkook

    2016-03-18

    The first total synthesis and structure revision of (-)-11β-hydroxycurvularin (1b), a macrolide possessing a β-hydroxyketone moiety, were accomplished. The β-hydroxyketone moiety in this natural product was introduced by cleavage of the N-O bond in an isoxazoline ring that was formed diastereoselectively in a 1,5-remote stereocontrolled fashion by employing intramolecular nitrile oxide cycloaddition.

  2. Asymmetric synthesis of functionalized trifluoromethyl-substituted pyrrolidines via an organocatalytic domino Michael/Mannich [3+2] cycloaddition.

    Science.gov (United States)

    Zhi, Ying; Zhao, Kun; Liu, Qiang; Wang, Ai; Enders, Dieter

    2016-11-29

    The asymmetric synthesis of highly functionalized pyrrolidine derivatives with three contiguous stereogenic centers and bearing a trifluoromethyl group has been developed through an organocatalytic domino Michael/Mannich [3+2] cycloaddition sequence. Employing a commercially available secondary amine as the catalyst, the scalable one-pot protocol occurs with high yields and excellent stereoselectivities, providing a short entry into a series of trifluoromethylated pyrrolidines with potential medical value.

  3. Nucleophile-directed selectivity towards linear carbonates in the niobium pentaethoxide-catalysed cycloaddition of CO2 and propylene oxide

    KAUST Repository

    Dutta, Barnali

    2014-01-01

    Homoleptic Nb-complexes combined with selected organic nucleophiles generate very active catalytic systems for the cycloaddition of propylene oxide and CO2 under ambient conditions. An unprecedented reaction pathway towards an acyclic organic carbonate is observed when extending the study to [Nb(OEt)5] in combination with 4-dimethylamino-pyridine (DMAP) or tetra-n-butylammonium bromide (TBAB). Mechanistic insights of the reaction are provided based on experimental and spectroscopic evidences. This journal is © the Partner Organisations 2014.

  4. Visible-light-induced formal [3+2] cycloaddition for pyrrole synthesis under metal-free conditions.

    Science.gov (United States)

    Xuan, Jun; Xia, Xu-Dong; Zeng, Ting-Ting; Feng, Zhu-Jia; Chen, Jia-Rong; Lu, Liang-Qiu; Xiao, Wen-Jing

    2014-05-26

    A photocatalytic formal [3+2] cycloaddition of 2H-azirines with alkynes has been achieved under irradiation by visible light in the presence of organic dye photocatalysts. This transformation provides efficient access to highly functionalized pyrroles in good yields and has been applied to the synthesis of drug analogues. A primary trial of photocascade catalysis merging energy transfer and redox neutral reactions was shown to be successful. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Quarternization of 3-azido-1-propyne oligomers obtained by copper(I-catalyzed azide–alkyne cycloaddition polymerization

    Directory of Open Access Journals (Sweden)

    Shun Nakano

    2015-06-01

    Full Text Available 3-Azido-1-propyne oligomer (oligoAP samples, prepared by copper(I-catalyzed azide–alkyne cycloaddition (CuAAC polymerization, were quarternized quantitatively with methyl iodide in sulfolane at 60 °C to obtain soluble oligomers. The conformation of the quarternized oligoAP in dilute DMSO-d6 solution was examined by pulse-field-gradient spin-echo NMR based on the touched bead model.

  6. Copper(I)-catalyzed cycloaddition of silver acetylides and azides: incorporation of volatile acetylenes into the triazole core.

    Science.gov (United States)

    Proietti Silvestri, Ilaria; Andemarian, Fikre; Khairallah, George N; Yap, Su Wan; Quach, Tim; Tsegay, Sammi; Williams, Craig M; O'Hair, Richard A J; Donnelly, Paul S; Williams, Spencer J

    2011-09-07

    Silver acetylides and organic azides react under copper(I) catalysis to afford 1,4-disubstituted 1,2,3-triazoles. Mechanistic studies implicate a process involving transmetallation to copper acetylides prior to cycloaddition. This work demonstrates that silver acetylides serve as suitable precursors for entry into copper-mediated coupling reactions. This methodology allows the incorporation of volatile and difficult-to-handle acetylenes into the triazole core.

  7. [3 + 3]-Cycloaddition of Donor-Acceptor Cyclopropanes with Nitrile Imines Generated in Situ: Access to Tetrahydropyridazines.

    Science.gov (United States)

    Garve, Lennart K B; Petzold, Martin; Jones, Peter G; Werz, Daniel B

    2016-02-01

    Donor-acceptor cyclopropanes are reacted under the influence of a Lewis acid with hydrazonyl chlorides to afford tetrahydropyridazines. Formally, this transformation can be regarded as a [3 + 3]-cycloaddition of three-membered rings and nitrile imines generated in situ. This efficient method provides fast access to a variety of structurally diverse pyridazine derivatives. The structure of a typical product was confirmed by X-ray crystallography.

  8. Enantioselective formal [3+3] cycloadditions of ketones and cyclic 1-azadienes by cascade enamine-enamine catalysis.

    Science.gov (United States)

    He, Xiao-Long; Xiao, You-Cai; Du, Wei; Chen, Ying-Chun

    2015-02-16

    An asymmetric formal [3+3] cycloaddition process with diversely structured aliphatic ketones and electron-deficient cyclic 1-azadienes was developed by cascade enamine-enamine catalysis of a cinchona-based primary amine. This sequence involved a domino Michael addition-Mannich reaction to afford spirocyclic architectures in excellent diastereo- and enantioselectivity. Importantly, high regioselectivity was realized for a number of unsymmetrical aliphatic ketone substrates.

  9. DFT study on the mechanism of InBr3-catalyzed [2+2] cycloaddition of allyltrimethylsilane with alkynones

    Indian Academy of Sciences (India)

    XING HUI ZHANG

    2017-04-01

    Density functional theory calculations at the M06-2X level were done to study the reaction mechanism and regioselectivity for the [2+2] cycloaddition of allyltrimethylsilane with alkynones using InBr₃ as the catalyst. The solvent effect was described by the single-point calculations with SMD model in 1,2-dichloroethane. The calculation results prove that the InBr₃-catalyzed cycloaddition of allyltrimethylsilane to alkynones takes place through two possible pathways and get selective cyclobutenone products. The reaction involves two main steps: attack of unsaturated carbon atoms of the alkynone by the π electrons of allyltrimethylsilane and a closed-loop process. The process of forming cyclobutenone product of silicon in the 2-position of the ketone group is more favored and the barrier is 15.5 kcal/mol, while the energies for the cyclobutenone of 3-position product are relatively high of 21.2 kcal/mol. In addition, we calculated the catalytic activity of the InX₃(X=Cl, Br, I) catalyst for this cycloaddition. This is a good explanation for the experimental data thatInBr₃ and InI₃ would be the most effective catalysts.

  10. Hydrophobic Encapsulated Phosphonium Salts-Synthesis of Weakly Coordinating Cations and their Application in Wittig Reactions.

    Science.gov (United States)

    Moritz, Ralf; Wagner, Manfred; Schollmeyer, Dieter; Baumgarten, Martin; Müllen, Klaus

    2015-06-15

    Large and rigid tetraarylphosphonium tetrafluoroborate salts have been synthesized representing weakly coordinating cations with diameters of several nanometers. Divergent dendritic growth by means of thermal Diels-Alder cycloaddition was employed for the construction of the hydrophobic polyphenylene framework up to the third generation. X-ray crystal structure analysis of first-generation phosphonium tetrafluoroborate supported the rigidity of the non-collapsible shell around the phosphorus center and gave insight into solid-state packing and cation-anion distances. Copper(I)-catalyzed azide-alkyne ligation served as reliable method for the preparation of a first-generation triazolylphenyl hybrid phosphonium cation under mild reaction conditions. Furthermore, from the synthesis of triarylbenzylphosphonium bromides, Wittig precursors with unprecedented bulky substituents in the α-position were accessible. Employment of these precursors under Wittig conditions by treatment with base and subsequent reaction with aldehydes preferentially provided (Z)-olefins with bulky polyphenylene substituents.

  11. Two-step functionalization of oligosaccharides using glycosyl iodide and trimethylene oxide and its applications to multivalent glycoconjugates.

    Science.gov (United States)

    Hsieh, Hsiao-Wu; Davis, Ryan A; Hoch, Jessica A; Gervay-Hague, Jacquelyn

    2014-05-19

    Oligosaccharide conjugates, such as glycoproteins and glycolipids, are potential chemotherapeutics and also serve as useful tools for understanding the biological roles of carbohydrates. With many modern isolation and synthetic technologies providing access to a wide variety of free sugars, there is increasing need for general methodologies for carbohydrate functionalization. Herein, we report a two-step methodology for the conjugation of per-O-acetylated oligosaccharides to functionalized linkers that can be used for various displays. Oligosaccharides obtained from both synthetic and commercial sources were converted to glycosyl iodides and activated with I2 to form reactive donors that were subsequently trapped with trimethylene oxide to form iodopropyl conjugates in a single step. The terminal iodide served as a chemical handle for further modification. Conversion into the corresponding azide followed by copper-catalyzed azide-alkyne cycloaddition afforded multivalent glycoconjugates of Gb3 for further investigation as anti-cancer therapeutics.

  12. Electrochemical Rectification of Redox Mediators Using Porphyrin-Based Molecular Multilayered Films on ITO Electrodes.

    Science.gov (United States)

    Civic, Marissa R; Dinolfo, Peter H

    2016-08-10

    Electrochemical charge transfer through multilayer thin films of zinc and nickel 5,10,15,20-tetra(4-ethynylphenyl) porphyrin constructed via copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry was examined. Current rectification toward various outer-sphere redox probes is revealed with increasing numbers of layers, as these films possess insulating properties over the neutral potential range of the porphyrin, then become conductive upon reaching its oxidation potential. Interfacial electron transfer rates of mediator-dye interactions toward [Co(bpy)3](2+), [Co(dmb)3](2+), [Co(NO2-phen)3](2+), [Fe(bpy)3](2+), and ferrocene (Fc), all outer-sphere redox species, were measured by hydrodynamic methods. The ability to modify electroactive films' interfacial electron transfer rates, as well as current rectification toward redox species, has broad applicability in a number of devices, particularly photovoltaics and photogalvanics.

  13. Phenanthroline-2,9-bistriazoles as selective G-quadruplex ligands

    DEFF Research Database (Denmark)

    Nielsen, Mads Corvinius; Larsen, Anders Foller; Abdikadir, Faisal Hussein

    2014-01-01

    G-quadruplex (G4) ligands are currently receiving considerable attention as potential anticancer therapeutics. A series of phenanthroline-2,9-bistriazoles carrying tethered positive end groups has been synthesized and evaluated as G4 stabilizers. The compounds were efficiently assembled by copper......(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in CH2Cl2 and water in the presence of a complexing agent. Characterization of the target compounds on telomeric and c-KIT G4 sequences led to the identification of guanidinium-substituted compounds as potent G4 DNA ligands with high selectivity over duplex DNA....... The diisopropylguanidium ligands exhibited high selectivity for the proto-oncogenic sequence c-KIT over the human telomeric sequence in the surface plasmon resonance (SPR) assay, whereas the compounds appeared potent on both G4 structures in the FRET melting temperature assay. The phenanthroline-2,9-bistriazole ligands...

  14. Diazo transfer for azido-functional surfaces

    Directory of Open Access Journals (Sweden)

    Laura Russo

    2011-04-01

    Full Text Available Preparation of azido-functionalized polymers is gaining increasing attention. We wish to report an innovative, novel strategy for azido functionalization of polymeric materials, coupling plasma technology and solution processed diazo transfer reactions. This novel approach allows the azido group to be introduced downstream of the material preparation, thus preserving its physicochemical and mechanical characteristics, which can be tailored a priori according to the desired application. The whole process involves the surface plasma functionalization of a material with primary amino groups, followed by a diazo transfer reaction, which converts the amino functionalities into azido groups that can be exploited for further chemoselective reactions. The diazo transfer reaction is performed in a heterogeneous phase, where the azido group donor is in solution. Chemical reactivity of the azido functionalities was verified by subsequent copper-catalyzed azide-alkyne cycloaddition.

  15. A one-pot-three-step route to triazolotriazepinoindazolones from oxazolino-2H-indazoles.

    Science.gov (United States)

    Conrad, Wayne E; Rodriguez, Kevin X; Nguyen, Huy H; Fettinger, James C; Haddadin, Makhluf J; Kurth, Mark J

    2012-08-03

    A one-pot-three-step method has been developed for the conversion of oxazolino-2H-indazoles into triazolotriazepinoindazolones with three points of diversity. Step one of this process involves a propargyl bromide-initiated ring opening of the oxazolino-2H-indazole (available by the Davis-Beirut reaction) to give an N(1)-(propargyl)-N(2)-(2-bromoethyl)-disubstituted indazolone, which then undergoes -CH(2)Br → -CH(2)N(3) displacement (step two) followed by an uncatalyzed intramolecular azide-alkyne 1,3-dipolar cycloaddition (step three) to form the target heterocycle. Employing 7-bromooxazolino-2H-indazole allows for further diversification through, for example, palladium-catalyzed coupling chemistry, as reported here.

  16. The Davis-Beirut reaction: N1,N2-disubstituted-1H-indazolones via 1,6-electrophilic addition to 3-alkoxy-2H-indazoles.

    Science.gov (United States)

    Conrad, Wayne E; Fukazawa, Ryo; Haddadin, Makhluf J; Kurth, Mark J

    2011-06-17

    A variety of electrophiles (anhydrides, acid chlorides, carbonochloridates, sulfonyl chlorides, and alkyl bromides) react with 3-methoxy-2H-indazole (1a), benzoxazin[3,2-b]indazole (1d), and oxazolino[3,2-b]indazole (1e) - substrates available by the Davis-Beirut reaction - to yield a diverse set of N(1),N(2)-disubstituted-1H-indazolones. With certain electrophiles, an AERORC (Addition of the Electrophile, Ring Opening, and Ring Closure) process on indazole 1d results in indazoloindazolone formation. An intriguing aspect of these N(1),N(2)-disubstituted-1H-indazolones is that they are poised for diversification through, for example, azide-alkyne cycloaddition chemistry reported here.

  17. Synthesis and Spectroscopic Evaluation of Two Novel Glycosylated Zinc(II)-Phthalocyanines.

    Science.gov (United States)

    Bächle, Felix; Hanack, Michael; Ziegler, Thomas

    2015-10-09

    In continuation of our work on glycoconjugated phthalocyanines, two new water soluble, non-ionic zinc(II) phthalocyanines have been prepared and fully characterized by means of ¹H-NMR, 13C-NMR, MALDI-TOF, ESI-TOF, UV-Vis spectroscopy, emission spectroscopy and fluorescence lifetime measurements. The carbohydrate-containing phthalonitrile precursors were synthesized through a copper-catalyzed azide-alkyne cycloaddition (CuAAC). The 2-methoxyethoxymethyl protecting group (MEM) was used to protect the carbohydrate moieties. It resisted the harsh basic cyclotetramerization conditions and could be easily cleaved under mild acidic conditions. The glycoconjugated zinc(II) phthalocyanines described here have molar extinction coefficents εmax>10⁵ m(-1) cm(-1) and absorption maxima λ>680 nm, which make them attractive photosensitizers for photo-dynamic therapy.

  18. Synthesis and Spectroscopic Evaluation of Two Novel Glycosylated Zinc(II-Phthalocyanines

    Directory of Open Access Journals (Sweden)

    Felix Bächle

    2015-10-01

    Full Text Available In continuation of our work on glycoconjugated phthalocyanines, two new water soluble, non-ionic zinc(II phthalocyanines have been prepared and fully characterized by means of 1H-NMR, 13C-NMR, MALDI-TOF, ESI-TOF, UV-Vis spectroscopy, emission spectroscopy and fluorescence lifetime measurements. The carbohydrate-containing phthalonitrile precursors were synthesized through a copper-catalyzed azide-alkyne cycloaddition (CuAAC. The 2-methoxyethoxymethyl protecting group (MEM was used to protect the carbohydrate moieties. It resisted the harsh basic cyclotetramerization conditions and could be easily cleaved under mild acidic conditions. The glycoconjugated zinc(II phthalocyanines described here have molar extinction coefficents εmax > 105 m−1 cm−1 and absorption maxima λ > 680 nm, which make them attractive photosensitizers for photo-dynamic therapy.

  19. Super-resolution optical DNA Mapping via DNA methyltransferase-directed click chemistry

    DEFF Research Database (Denmark)

    Vranken, Charlotte; Deen, Jochem; Dirix, Lieve

    2014-01-01

    We demonstrate an approach to optical DNA mapping, which enables near single-molecule characterization of whole bacteriophage genomes. Our approach uses a DNA methyltransferase enzyme to target labelling to specific sites and copper-catalysed azide-alkyne cycloaddition to couple a fluorophore...... to the DNA. We achieve a labelling efficiency of ∼70% with an average labelling density approaching one site every 500 bp. Such labelling density bridges the gap between the output of a typical DNA sequencing experiment and the long-range information derived from traditional optical DNA mapping. We lay...... the foundations for a wider-scale adoption of DNA mapping by screening 11 methyltransferases for their ability to direct sequence-specific DNA transalkylation; the first step of the DNA labelling process and by optimizing reaction conditions for fluorophore coupling via a click reaction. Three of 11 enzymes...

  20. Design, Synthesis, and Cytotoxicity of Perbutyrylated Glycosides of 4β-Triazolopodophyllotoxin Derivatives

    Directory of Open Access Journals (Sweden)

    Cheng-Ting Zi

    2015-02-01

    Full Text Available A series of novel perbutyrylated glycosides of 4β-triazolopodophyllotoxin derivatives were synthesized by utilizing the copper-catalyzed azide-alkyne cycloaddition (CuAAC reaction. Evaluation of cytotoxicity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480 using the MTT assay shows that some of these glycosylated derivatives have good anticancer activity. Among the synthesized compounds, compound 21a shows the highest activity, with IC50 values ranging from 0.49 to 6.70 μM, which is more potent than the control drugs etoposide and cisplatin. Compound 21a is characterized by a perbutyrylated α-D(+-galactosyl residue, the absence of an additional linking spacer between the sugar residue and the triazole ring, as well as a 4'-OH group on the E ring of the podophyllotoxin scaffold.

  1. Click Chemistry Immobilization of Antibodies on Polymer Coated Gold Nanoparticles.

    Science.gov (United States)

    Finetti, Chiara; Sola, Laura; Pezzullo, Margherita; Prosperi, Davide; Colombo, Miriam; Riva, Benedetta; Avvakumova, Svetlana; Morasso, Carlo; Picciolini, Silvia; Chiari, Marcella

    2016-07-26

    The goal of this work is to develop an innovative approach for the coating of gold nanoparticles (AuNPs) with a synthetic functional copolymer. This stable coating with a thickness of few nanometers provides, at the same time, stabilization and functionalization of the particles. The polymeric coating consists of a backbone of polydimethylacrylamide (DMA) functionalized with an alkyne monomer that allows the binding of azido modified molecules by Cu(I)-catalyzed azide/alkyne 1,3-dipolar cycloaddition (CuAAC, click chemistry). The thin polymer layer on the surface stabilizes the colloidal suspension whereas the alkyne functions pending from the backbone are available for the reaction with azido-modified proteins. The reactivity of the coating is demonstrated by immobilizing an azido modified anti-mouse IgG antibody on the particle surface. This approach for the covalent binding of antibody to a gold-NPs is applied to the development of gold labels in biosensing techniques.

  2. Synthesis of double-clickable functionalised graphene oxide for biological applications.

    Science.gov (United States)

    Mei, Kuo-Ching; Rubio, Noelia; Costa, Pedro M; Kafa, Houmam; Abbate, Vincenzo; Festy, Frederic; Bansal, Sukhvinder S; Hider, Robert C; Al-Jamal, Khuloud T

    2015-10-18

    Azide- and alkyne-double functionalised graphene oxide (Click(2) GO) was synthesised and characterised with attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA) and Raman spectroscopy. Fourteen-percentage increase in azide content was found, after pre-treatment of GO with meta-chloroperoxybenzoic acid (mCPBA), determined with elemental analysis. No effect on A549 cell viability was found, up to 100 μg mL(-1) and 72 h of incubation, determined with the modified lactate dehydrogenase (mLDH) assay. Two sequential copper(i) catalysed azide-alkyne cycloaddition (CuAAC) reactions were performed to conjugate the propargyl-modified blood-brain barrier targeting peptide Angiopep-2, and a bis-azide polyethylene glycol (MW = 3500), to the Click(2) GO. The final conjugate was characterised with ATR-FTIR and TGA.

  3. Immobilization of cobalt(II) Schiff base complexes on polystyrene resin and a study of their catalytic activity for the aerobic oxidation of alcohols.

    Science.gov (United States)

    Jain, Suman; Reiser, Oliver

    2008-01-01

    The copper-catalyzed [3+2] azide-alkyne cycloaddition and the Staudinger ligation are readily applicable and highly efficient for the immobilization of cobalt Schiff base complexes onto polystyrene resins. Stepwise synthesis of polymer-bound Schiff bases followed by their subsequent complexation with metal ions were successfully carried out. Direct covalent attachment of preformed homogeneous cobalt Schiff base complexes to the resins was also possible. The catalytic efficiency of the so-prepared polystyrene-bound cobalt Schiff bases was studied for the oxidation of alcohols to carbonyl compounds using molecular oxygen as oxidant. The immobilized complexes were highly efficient and even more reactive than the corresponding homogenous analogues, thus affording better yields of oxidized products within shorter reaction times. The supported catalysts could easily be recovered from the reaction mixture by simple filtration and reused for subsequent experiments with consistent catalytic activity.

  4. Influence of azide incorporation on binding affinity by small papain inhibitors.

    Science.gov (United States)

    Wammes, Angelique E M; Hendriks, Tom G; Amatdjais-Groenen, Helene I V; Wijdeven, Marloes A; van Hest, Jan C M; van Delft, Floris L; Ritschel, Tina; Rutjes, Floris P J T

    2014-10-15

    In order to develop affinity-based biosensor platforms, appropriate ligands with a functional handle for immobilization onto a biosensor surface are required. To this end, a library of papain inhibitors was designed and synthesized, containing different azide linkers for subsequent immobilization by 'click' chemistry, in this particular case by copper-free, strain-promoted azide-alkyne cycloaddition (SPAAC). Furthermore, a molecular docking study was performed to obtain a better insight as to at which position such azide handles could be tolerated without affecting binding affinity. Although the azide moiety is small, in some cases its introduction strongly influenced the binding affinity. For one class of inhibitors a swapped binding mode was proposed to explain the results. In addition, a specific site for linker introduction was identified, which did not significantly affect the binding affinity.

  5. Synthesis and biological evaluation of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles as transforming growth factor-β type 1 receptor kinase inhibitors.

    Science.gov (United States)

    Li, Fei; Park, Yunjeong; Hah, Jung-Mi; Ryu, Jae-Sang

    2013-02-15

    A series of 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles has been synthesized and evaluated for their ALK5 inhibitory activity. The 1-(6-methylpyridin-2-yl)-1,2,3-triazoles were assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition. Following this, quinoxaline was introduced through Pd-catalyzed direct arylation. The synthesized 1-(6-methylpyridin-2-yl)-5-(quinoxalin-6-yl)-1,2,3-triazoles revealed significant selectivity differences with respect to p38α MAP kinase. In particular, 12k showed 80.8% ALK5 inhibitory activity at a concentration of 10 μM and IC(50) value of 4.69 μM, but did not show p38α MAP kinase inhibitory activity (-1.94% inhibition at a concentration of 10 μM).

  6. Synthesis of 2-(4-Aminomethyl-1H-1,2,3-Triazole-1-yl-1,4-Naphthoquinone Derivatives

    Directory of Open Access Journals (Sweden)

    Wagner O. Valença

    2012-06-01

    Full Text Available In this work, were synthesized 18 new compounds based on 1H-1,2,3-triazole-1,4-naphthoquinones via Cu-AAC (Cu-catalyzed Azide Alkyne Cycloaddition reaction. The compounds (2-7(a-c were obtained in moderate-to-good yields (43-99%. Two methodologies were employed to obtain 2-(4-aminomethyl-1H-1,2,3-triazol-1-yl-1,4-naphthoquinone derivatives. Firstly, we using the Method A (CH3CN/CuI/r.t./20h, but some compounds presented moderate yields of 43-60%. Fortunately, when we applied the Method B (DMF/Et3N/ultrasound, were obtained yields between 78 and 92%.

  7. Synthesis of 1,2,3-Triazole Derivatives and in Vitro Antifungal Evaluation on Candida Strains

    Directory of Open Access Journals (Sweden)

    Almir G. Wanderley

    2012-05-01

    Full Text Available 1,2,3-Triazoles have been extensively studied as compounds possessing important biological activities. In this work, we describe the synthesis of ten 2-(1-aryl-1H-1,2,3-triazol-4-ylpropan-2-ols via copper catalyzed azide alkyne cycloaddition (CuAAc or click chemistry. Next the in vitro antifungal activity of these ten compounds was evaluated using the microdilution broth method against 42 isolates of four different Candida species. Among all tested compounds, the halogen substituted triazole 2-[1-(4-chlorophenyl-1H-(1,2,3triazol-4-yl]propan-2-ol, revealed the best antifungal profile, showing that further modifications could be done in the structure to obtain a better drug candidate in the future.

  8. Preparation of fluorescent organometallic porphyrin complex nanogels of controlled molecular structure via reverse-emulsion click chemistry.

    Science.gov (United States)

    Fu, Guo-Dong; Jiang, Hua; Yao, Fang; Xu, Li-Qun; Ling, Jun; Kang, En-Tang

    2012-09-26

    Here, we are the first to report a novel approach to preparing well-defined poly(ethylene glycol) (PEG) fluorescent nanogels, with well-defined molecular structures and desired functionalities via reverse (mini)emulsion copper(I)-catalyzed azide-alkyne cycloaddition (REM-CuAAC). Nanogels with hydroxyl groups and Ga-porphyrin complex (Ga-porphyrin-OH nanogels), as well as with Ga-porphyrin complex and folate functional groups (Ga-porphyrin-FA), are successfully prepared. Nanogels of 30 and 120 nm in diameter are obtained and they exhibit an emission maxima within the wavelength range 700-800 nm. The nanogels could find uses in near infrared (NIR) imaging attributable to their fluorescence and their functionality for cell affinity.

  9. Carbohydrate CuAAC click chemistry for therapy and diagnosis.

    Science.gov (United States)

    He, Xiao-Peng; Zeng, Ya-Li; Zang, Yi; Li, Jia; Field, Robert A; Chen, Guo-Rong

    2016-06-24

    Carbohydrates are important as signaling molecules and for cellular recognition events, therefore offering scope for the development of carbohydrate-mimetic diagnostics and drug candidates. As a consequence, the construction of carbohydrate-based bioactive compounds and sensors has become an active research area. While the advent of click chemistry has greatly accelerated the progress of medicinal chemistry and chemical biology, recent literature has seen an extensive use of such approaches to construct functionally diverse carbohydrate derivatives. Here we summarize some of the progress, covering the period 2010 to mid-2015, in Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition CuAAC "click chemistry" of carbohydrate derivatives, in the context of potential therapeutic and diagnostic tool development.

  10. Synthesis of novel 1H-1,2,3-triazole tethered C-5 substituted uracil-isatin conjugates and their cytotoxic evaluation

    KAUST Repository

    Kumar, Kewal

    2012-12-01

    The present manuscript describes the synthesis of uracil-isatin hybrids via azide-alkyne cycloadditions and their cytotoxic evaluation against three human cancer cell lines viz. HeLa (cervix), MCF-7 (breast) and DU145 (prostate) using MTT assay. The evaluation studies revealed the dependence of cytotoxicity on C-5 substituents of both uracil and isatin as well as the alkyl chain length with compounds 6g and 6k showing IC50 values 18.21 and 13.90 μM respectively against DU145 cell lines. Most of the synthesized conjugates exhibited considerable selectivity against MCF-7 and DU145 cell lines. © 2012 Elsevier Masson SAS. All rights reserved.

  11. Conjugating folate on superparamagnetic Fe3O4@Au nanoparticles using click chemistry

    Science.gov (United States)

    Shen, Xiaofang; Ge, Zhaoqiang; Pang, Yuehong

    2015-02-01

    Gold-coated magnetic core@shell nanoparticles, which exhibit magneto-optical properties, not only enhance the chemical stability of core and biocompatibility of surface, but also provide a combination of multimodal imaging and therapeutics. The conjugation of these tiny nanoparticles with specific biomolecules allows researchers to target the desired location. In this paper, superparamagnetic Fe3O4@Au nanoparticles were synthesized and functionalized with the azide group on the surface by formation of self-assembled monolayers. Folate (FA) molecules, non-immunogenic target ligands for cancer cells, are conjugated with alkyne and then immobilized on the azide-terminated Fe3O4@Au nanoparticles through copper(I)-catalyzed azide-alkyne cycloaddition (click reaction). Myelogenous leukemia K562 cells were used as a folate receptor (FR) model, which can be targeted and extracted by magnetic field after interaction with the Fe3O4@Au-FA nanoparticles.

  12. A versatile approach for the site-specific modification of recombinant antibodies using a combination of enzyme-mediated bioconjugation and click chemistry.

    Science.gov (United States)

    Alt, Karen; Paterson, Brett M; Westein, Erik; Rudd, Stacey E; Poniger, Stan S; Jagdale, Shweta; Ardipradja, Katie; Connell, Timothy U; Krippner, Guy Y; Nair, Ashish K N; Wang, Xiaowei; Tochon-Danguy, Henri J; Donnelly, Paul S; Peter, Karlheinz; Hagemeyer, Christoph E

    2015-06-22

    A unique two-step modular system for site-specific antibody modification and conjugation is reported. The first step of this approach uses enzymatic bioconjugation with the transpeptidase Sortase A for incorporation of strained cyclooctyne functional groups. The second step of this modular approach involves the azide-alkyne cycloaddition click reaction. The versatility of the two-step approach has been exemplified by the selective incorporation of fluorescent dyes and a positron-emitting copper-64 radiotracer for fluorescence and positron-emission tomography imaging of activated platelets, platelet aggregates, and thrombi, respectively. This flexible and versatile approach could be readily adapted to incorporate a large array of tailor-made functional groups using reliable click chemistry whilst preserving the activity of the antibody or other sensitive biological macromolecules.

  13. Click chemistry for rapid labeling and ligation of RNA.

    Science.gov (United States)

    Paredes, Eduardo; Das, Subha R

    2011-01-03

    The copper(I)-promoted azide-alkyne cycloaddition reaction (click chemistry) is shown to be compatible with RNA (with free 2'-hydroxyl groups) in spite of the intrinsic lability of RNA. RNA degradation is minimized through stabilization of the Cu(I) in aqueous buffer with acetonitrile as cosolvent and no other ligand; this suggests the general possibility of "ligandless" click chemistry. With the viability of click chemistry validated on synthetic RNA bearing "click"-reactive alkynes, the scope of the reaction is extended to in-vitro-transcribed or, indeed, any RNA, as a click-reactive azide is incorporated enzymatically. Once clickable groups are installed on RNA, they can be rapidly click labeled or conjugated together in click ligations, which may be either templated or nontemplated. In click ligations the resultant unnatural triazole-linked RNA backbone is not detrimental to RNA function, thus suggesting a broad applicability of click chemistry in RNA biological studies.

  14. Copper-free click-chemistry platform to functionalize cisplatin prodrugs.

    Science.gov (United States)

    Pathak, Rakesh K; McNitt, Christopher D; Popik, Vladimir V; Dhar, Shanta

    2014-06-02

    The ability to rationally design and construct a platform technology to develop new platinum(IV) [Pt(IV)] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities considering the sensitivity of Pt(IV) centers, we used a strain-promoted azide-alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single Pt(IV) precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated.

  15. Spatially Directional Resorcin[4]arene Cavitand Glycoconjugates for Organic Catalysis.

    Science.gov (United States)

    Husain, Ali A; Maknenko, Arthur M; Bisht, Kirpal S

    2016-04-25

    The synthesis of novel spatially directional multivalent resorcin[4]arene cavitand glycoconjugates (RCGs) and their ability to catalyze organic reactions is reported. The β-d-glucopyranoside moieties on the upper rim of the "bowl"-shaped resorcin[4]arene cavitand core are capable of multiple hydrogen-bond interactions resulting in a pseudo-cavity, which has been investigated for organic transformations in aqueous media. The RCGs have been demonstrated to catalyze thiazole formation, thiocyanation, copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), and Mannich reactions; they impart stereoselectivity in the three-component Mannich reaction. Thermodynamic values obtained from (1) H diffusion-ordered spectroscopy (DOSY) experiments suggest that the upper saccharide cavity of the RCG and not the resorcin[4]arene cavity is the site of the complexation event.

  16. Functional Biomimetic Architectures

    Science.gov (United States)

    Levine, Paul M.

    N-substituted glycine oligomers, or 'peptoids,' are a class of sequence--specific foldamers composed of tertiary amide linkages, engendering proteolytic stability and enhanced cellular permeability. Peptoids are notable for their facile synthesis, sequence diversity, and ability to fold into distinct secondary structures. In an effort to establish new functional peptoid architectures, we utilize the copper-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) reaction to generate peptidomimetic assemblies bearing bioactive ligands that specifically target and modulate Androgen Receptor (AR) activity, a major therapeutic target for prostate cancer. Additionally, we explore chemical ligation protocols to generate semi-synthetic hybrid biomacromolecules capable of exhibiting novel structures and functions not accessible to fully biosynthesized proteins.

  17. Poly(Ethylene Glycol-Based Backbones with High Peptide Loading Capacities

    Directory of Open Access Journals (Sweden)

    Aoife O'Connor

    2014-10-01

    Full Text Available Polymer-peptide conjugates are a promising class of compounds, where polymers can be used to overcome some of the limitations associated with peptides intended for therapeutic and/or diagnostic applications. Linear polymers such as poly(ethylene glycol can be conjugated through terminal moieties and have therefore limited loading capacities. In this research, functionalised linear poly(ethylene glycols are utilised for peptide conjugation, to increase their potential loading capacities. These poly(ethylene glycol derivatives are conjugated to peptide sequences containing representative side-chain functionalised amino acids, using different conjugation chemistries, including copper-catalysed azide-alkyne cycloaddition, amide coupling and thiol-ene reactions. Conjugation of a sequence containing the RGD motif to poly(allyl glycidyl ether by the thiol-ene reaction, provided a conjugate which could be used in platelet adhesion studies.

  18. Labeling Live Cells by Copper-Catalyzed Alkyne-Azide Click Chemistry

    Science.gov (United States)

    Hong, Vu; Steinmetz, Nicole F.; Manchester, Marianne

    2010-01-01

    The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, optimized for biological molecules in aqueous buffers, has been shown to rapidly label mammalian cells in culture with no loss in cell viability. Metabolic uptake and display of the azide derivative of N-acetylmannosamine developed by Bertozzi, followed by CuAAC ligation using sodium ascorbate and the ligand tris(hydroxypropyltriazolyl)methylamine (THPTA), gave rise to abundant covalent attachment of dye-alkyne reactants. THPTA serves both to accelerate the CuAAC reaction and to protect the cells from damage by oxidative agents produced by the Cu-catalyzed reduction of oxygen by ascorbate, which is required to maintain the metal in the active +1 oxidation state. This procedure extends the application of this fastest of azide-based bioorthogonal reactions to the exterior of living cells. PMID:20886827

  19. Synthesis and luminescence properties of iridium(III) azide- and triazole-bisterpyridine complexes.

    Science.gov (United States)

    Goldstein, Daniel C; Peterson, Joshua R; Cheng, Yuen Yap; Clady, Raphael G C; Schmidt, Timothy W; Thordarson, Pall

    2013-07-26

    We describe here the synthesis of azide-functionalised iridium(III) bisterpyridines using the "chemistry on the complex" strategy. The resulting azide-complexes are then used in the copper(I)-catalysed azide-alkyne Huisgen 1,3-dipolar cycloaddition "click chemistry" reaction to from the corresponding triazole-functionalised iridium(III) bisterpyridines. The photophysical characteristics, including lifetimes, of these compounds were also investigated. Interestingly, oxygen appears to have very little effect on the lifetime of these complexes in aqueous solutions. Unexpectedly, sodium ascorbate acid appears to quench the luminescence of triazole-functionalised iridium(III) bisterpyridines, but this effect can be reversed by the addition of copper(II) sulfate, which is known to oxidize ascorbate under aerobic conditions. The results demonstrate that iridium(III) bisterpyridines can be functionalized for use in "click chemistry" facilitating the use of these photophysically interesting complexes in the modification of polymers or surfaces, to highlight just two possible applications.

  20. Copper-chelating azides for efficient click conjugation reactions in complex media.

    Science.gov (United States)

    Bevilacqua, Valentina; King, Mathias; Chaumontet, Manon; Nothisen, Marc; Gabillet, Sandra; Buisson, David; Puente, Céline; Wagner, Alain; Taran, Frédéric

    2014-06-02

    The concept of chelation-assisted copper catalysis was employed for the development of new azides that display unprecedented reactivity in the copper(I)-catalyzed azide-alkyne [3+2] cycloaddition (CuAAC) reaction. Azides that bear strong copper-chelating moieties were synthesized; these functional groups allow the formation of azide copper complexes that react almost instantaneously with alkynes under diluted conditions. Efficient ligation occurred at low concentration and in complex media with only one equivalent of copper, which improves the biocompatibility of the CuAAC reaction. Furthermore, such a click reaction allowed the localization of a bioactive compound inside living cells by fluorescence measurements. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Resin-Supported Catalysts for CuAAC Click Reactions in Aqueous or Organic Solvents

    Science.gov (United States)

    Presolski, Stanislav I.; Mamidyala, Sreeman K.; Manzenrieder, Florian

    2012-01-01

    The copper-catalyzed azide-alkyne cycloaddition click reaction is a valuable process for the synthesis of libraries of drug candidates, derivatized polymers and materials, and a wide variety of other functional molecules. In some circumstances, the removal of the copper catalyst is both necessary and inconvenient. We describe here two immobilized forms of a Cu-binding ligand that has been shown to accelerate triazole formation under many different conditions, using different resin supports that are appropriate for aqueous or organic solvents. Copper leaching from these resins was modest, allowing them to be reused in many reaction/filtration cycles without recharging with metal ion. The utility of this catalyst form was demonstrated in the convenient synthesis of 20 N-acetylgalactosamine derivatives for biological testing. PMID:22946559

  2. Labeling live cells by copper-catalyzed alkyne--azide click chemistry.

    Science.gov (United States)

    Hong, Vu; Steinmetz, Nicole F; Manchester, Marianne; Finn, M G

    2010-10-20

    The copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, optimized for biological molecules in aqueous buffers, has been shown to rapidly label mammalian cells in culture with no loss in cell viability. Metabolic uptake and display of the azide derivative of N-acetylmannosamine developed by Bertozzi, followed by CuAAC ligation using sodium ascorbate and the ligand tris(hydroxypropyltriazolyl)methylamine (THPTA), gave rise to abundant covalent attachment of dye-alkyne reactants. THPTA serves both to accelerate the CuAAC reaction and to protect the cells from damage by oxidative agents produced by the Cu-catalyzed reduction of oxygen by ascorbate, which is required to maintain the metal in the active +1 oxidation state. This procedure extends the application of this fastest of azide-based bioorthogonal reactions to the exterior of living cells.

  3. Stepwise, Protecting Group Free Synthesis of [4]Rotaxanes

    Directory of Open Access Journals (Sweden)

    James E. M. Lewis

    2017-01-01

    Full Text Available Despite significant advances in the last three decades towards high yielding syntheses of rotaxanes, the preparation of systems constructed from more than two components remains a challenge. Herein we build upon our previous report of an active template copper-catalyzed azide-alkyne cycloaddition (CuAAC rotaxane synthesis with a diyne in which, following the formation of the first mechanical bond, the steric bulk of the macrocycle tempers the reactivity of the second alkyne unit. We have now extended this approach to the use of 1,3,5-triethynylbenzene in order to successively prepare [2]-, [3]- and [4]rotaxanes without the need for protecting group chemistry. Whilst the first two iterations proceeded in good yield, the steric shielding that affords this selectivity also significantly reduces the efficacy of the active template (AT-CuAAC reaction of the third alkyne towards the preparation of [4]rotaxanes, resulting in severely diminished yields.

  4. Synthesis of novel 1H-1,2,3-triazole tethered C-5 substituted uracil-isatin conjugates and their cytotoxic evaluation.

    Science.gov (United States)

    Kumar, Kewal; Sagar, Sunil; Esau, Luke; Kaur, Mandeep; Kumar, Vipan

    2012-12-01

    The present manuscript describes the synthesis of uracil-isatin hybrids via azide-alkyne cycloadditions and their cytotoxic evaluation against three human cancer cell lines viz. HeLa (cervix), MCF-7 (breast) and DU145 (prostate) using MTT assay. The evaluation studies revealed the dependence of cytotoxicity on C-5 substituents of both uracil and isatin as well as the alkyl chain length with compounds 6g and 6k showing IC(50) values 18.21 and 13.90 μM respectively against DU145 cell lines. Most of the synthesized conjugates exhibited considerable selectivity against MCF-7 and DU145 cell lines. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  5. Peptide-LNA oligonucleotide conjugates

    DEFF Research Database (Denmark)

    Astakhova, I Kira; Hansen, Lykke Haastrup; Vester, Birte

    2013-01-01

    properties, peptides were introduced into oligonucleotides via a 2'-alkyne-2'-amino-LNA scaffold. Derivatives of methionine- and leucine-enkephalins were chosen as model peptides of mixed amino acid content, which were singly and doubly incorporated into LNA/DNA strands using highly efficient copper......Although peptide-oligonucleotide conjugates (POCs) are well-known for nucleic acids delivery and therapy, reports on internal attachment of peptides to oligonucleotides are limited in number. To develop a convenient route for preparation of internally labeled POCs with improved biomedical......(i)-catalyzed azide-alkyne cycloaddition (CuAAC) "click" chemistry. DNA/RNA target binding affinity and selectivity of the resulting POCs were improved in comparison to LNA/DNA mixmers and unmodified DNA controls. This clearly demonstrates that internal attachment of peptides to oligonucleotides can significantly...

  6. Novel peptide-based protease inhibitors

    DEFF Research Database (Denmark)

    Roodbeen, Renée

    This thesis describes the design and synthesis of peptide-based serine protease inhibitors. The targeted protease, urokinase-type plasminogen activator (uPA) activates plasminogen, which plays a major role in cancer metastasis. The peptide upain-2 (S 1 ,S 12-cyclo-AcCSWRGLENHAAC-NH2) is a highly......, the disulfide bridge was replaced with amide bonds of various lengths. The novel peptides did not retain their inhibitory activity, but formed the basis for another strategy. Second, bicyclic peptides were obtained by creating head-to-tail cyclized peptides that were made bicyclic by the addition of a covalent...... increased. Finally, the effect of multivalent display of upain-2 was investigated. Several dimers of upain-2 were made and the attachment of upain-2 via the Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) onto an alkyne functionalized carbohydrate scaffold was investigated. Besides the synthesis...

  7. Sequence-selective DNA recognition and enhanced cellular up-take by peptide-steroid conjugates.

    Science.gov (United States)

    Ruiz García, Yara; Iyer, Abhishek; Van Lysebetten, Dorien; Pabon, Y Vladimir; Louage, Benoit; Honcharenko, Malgorzata; De Geest, Bruno G; Smith, C I Edvard; Strömberg, Roger; Madder, Annemieke

    2015-12-25

    Several GCN4 bZIP TF models have previously been designed and synthesized. However, the synthetic routes towards these constructs are typically tedious and difficult. We here describe the substitution of the Leucine zipper domain of the protein by a deoxycholic acid derivative appending the two GCN4 binding region peptides through an optimized double azide-alkyne cycloaddition click reaction. In addition to achieving sequence specific dsDNA binding, we have investigated the potential of these compounds to enter cells. Confocal microscopy and flow cytometry show the beneficial influence of the steroid on cell uptake. This unique synthetic model of the bZIP TF thus combines sequence specific dsDNA binding properties with enhanced cell-uptake. Given the unique properties of deoxycholic acid and the convergent nature of the synthesis, we believe this work represents a key achievement in the field of TF mimicry.

  8. Synthesis of Phospholipid-Protein Conjugates as New Antigens for Autoimmune Antibodies

    Directory of Open Access Journals (Sweden)

    Arindam Maity

    2015-06-01

    Full Text Available Copper(I-catalyzed azide-alkyne cycloaddition, or CuAAC click chemistry, is an efficient method for bioconjugation aiming at chemical and biological applications. Herein, we demonstrate how the CuAAC method can provide novel phospholipid-protein conjugates with a high potential for the diagnostics and therapy of autoimmune conditions. In doing this, we, for the first time, covalently bind via 1,2,3-triazole linker biologically complementary molecules, namely phosphoethanol amine with human β2-glycoprotein I and prothrombin. The resulting phospholipid-protein conjugates show high binding affinity and specificity for the autoimmune antibodies against autoimmune complexes. Thus, the development of this work might become a milestone in further diagnostics and therapy of autoimmune diseases that involve the production of autoantibodies against the aforementioned phospholipids and proteins, such as antiphospholipid syndrome and systemic lupus erythematosus.

  9. Boron Drug Delivery via Encapsulated Magnetic Nanocomposites: A New Approach for BNCT in Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Yinghuai Zhu

    2010-01-01

    Full Text Available Ortho-carborane cages have been successfully attached to modified magnetic nanoparticles via catalytic azide-alkyne cycloadditions between 1-R-2-butyl-Ortho-C2B10H10(R=Me,3;Ph,4 and propargyl group-enriched magnetic nanoparticles. A loading amount of 9.83 mmol boron atom/g starch-matrixed magnetic nanoparticles has been reached. The resulting nanocomposites have been found to be highly tumor-targeted vehicles under the influence of an external magnetic field (1.14T, yielding a high boron concentration of 51.4 μg/g tumor and ratios of around 10 : 1 tumor to normal tissues.

  10. Soluble organic nanotubes for catalytic systems

    Science.gov (United States)

    Xiong, Linfeng; Yang, Kunran; Zhang, Hui; Liao, Xiaojuan; Huang, Kun

    2016-03-01

    In this paper, we report a novel method for constructing a soluble organic nanotube supported catalyst system based on single-molecule templating of core-shell bottlebrush copolymers. Various organic or metal catalysts, such as sodium prop-2-yne-1-sulfonate (SPS), 1-(2-(prop-2-yn-1-yloxy)ethyl)-1H-imidazole (PEI) and Pd(OAc)2 were anchored onto the tube walls to functionalize the organic nanotubes via copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction. Depending on the ‘confined effect’ and the accessible cavity microenvironments of tubular structures, the organic nanotube catalysts showed high catalytic efficiency and site-isolation features. We believe that the soluble organic nanotubes will be very useful for the development of high performance catalyst systems due to their high stability of support, facile functionalization and attractive textural properties.

  11. A Peptoid-Based Fluorescent Sensor for Cyanide Detection

    Directory of Open Access Journals (Sweden)

    Bumhee Lim

    2016-03-01

    Full Text Available Peptoids, N-substituted glycine oligomers, are versatile peptidomimetics with diverse biomedical applications. However, strategies to the development of novel fluorescent peptoids as chemical sensors have not been extensively explored, yet. Here, we synthesized a novel peptoid-based fluorescent probe in which a coumarin moiety was incorporated via copper(I-catalyzed azide-alkyne cycloaddition reaction. Fluorescence of the newly generated coumarin-peptoid was dramatically quenched upon coordination of the Cu2+ ion, and the resulting peptoid-Cu2+ complex exhibited significant Turn-ON fluorescence following the addition of CN−. The rapid and reversible response, combined with cyanide selectivity of the synthesized peptoid, reflects a multistep photo-process and supports its utility as a new type of CN− sensor.

  12. Determination of flumioxazin residue in food samples through a sensitive fluorescent sensor based on click chemistry.

    Science.gov (United States)

    Lu, Lijun; Yang, Linlin; Cai, Huijian; Zhang, Lan; Lin, Zhenyu; Guo, Longhua; Qiu, Bin; Chen, Guonan

    2014-11-01

    A sensitive and selective fluorescent sensor for flumioxazin was designed based on the formation of strong fluorescence compound (1,2,3-triazole compounds) via the reaction of the alkynyl group in flumioxazin with 3-azido-7-hydroxycoumarin, a weak-fluorescent compound, through the Cu(+)-catalysed azide-alkyne cycloaddition (CuAAC) reaction. The fluorescence increase factor (represented by F/F0) of the system exhibited a good linear relationship with the concentrations of flumioxazin in the range of 0.25-6.0 μg/L with a detection limit of 0.18 μg/L (S/N=3). Also, the proposed fluorescent sensor demonstrated good selectivity for flumioxazin assay even in the presence of high concentration of other pesticides. Based on such high sensitivity and selectivity, the proposed fluorescent sensor has been applied to test the flumioxazin residue in some vegetable and water samples with satisfied results.

  13. Synthesis and phytotoxic activity of 1,2,3-triazole derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Borgati, Thiago F.; Alves, Rosemeire B., E-mail: thfborgati@gmail.com, E-mail: rosebrondi@yahoo.com.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Quimica; Teixeira, Robson R.; Freitas, Rossimiriam P. de; Perdigao, Thays G.; Silva, Silma F. da; Santos, Aline Aparecida dos [Universidade Federal de Vicosa, MG (Brazil). Departamento de Quimica; Bastidas, Alberto de Jesus O. [Laboratorio de Quimica Ecologica, Departamento de Quimica, Universidad de Los Andes, Nucleo Universitario Pedro Rincon Gutierrez, Merida (Viet Nam)

    2013-06-15

    Thirteen triazole derivatives bearing halogenated benzyl substituents were synthesized using the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), a leading example of the click chemistry approach, as the key step. The biological activity of the compounds was evaluated, and it was found that these compounds interfere with the germination and radicle growth (shoots and roots) of two dicotyledonous species, Lactuca sativa and Cucumis sativus, and one monocotyledonous species, Allium cepa. The compounds showed predominantly inhibitory activity related to the evaluated species mainly at the concentration of 10{sup -4} mol L{sup -1}. Some of them presented inhibitory activity comparable to 2,4-D (2,4-dichlorophenoxyacetic acid), used as positive control. (author)

  14. Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors

    DEFF Research Database (Denmark)

    Ek, Pramod Kumar; Jølck, Rasmus Irming; Andresen, Thomas Lars

    2015-01-01

    at the micelle shell using CuAAC results in a stabilized micelle pH nanosensor. Compared to the postmicelle modification strategy, the mixed-micellization approach increases the control of the overall composition of the nanosensors.Both approaches provide stable nanosensors with similar pKa profiles and thereby......The design flexibility that polymeric micelles offer in the fabrication of optical nanosensors for ratiometric pH measurements is investigated. pH nanosensors based on polymeric micelles are synthesized either by a mixed-micellization approach or by a postmicelle modification strategy. In the mixed......-micellization approach, self-assembly of functionalized unimers followed by shell cross-linking by copper-catalyzed azide-alkyne cycloaddition (CuAAC) results in stabilized cRGD-functionalized micelle pH nanosensors. In the postmicelle modification strategy, simultaneous cross-linking and fluorophore conjugation...

  15. EdU Incorporation for FACS and Microscopy Analysis of DNA Replication in Budding Yeast.

    Science.gov (United States)

    Talarek, Nicolas; Petit, Julie; Gueydon, Elisabeth; Schwob, Etienne

    2015-01-01

    DNA replication is a key determinant of chromosome segregation and stability in eukaryotes. The yeast Saccharomyces cerevisiae has been extensively used for cell cycle studies, yet simple but key parameters such as the fraction of cells in S phase in a population or the subnuclear localization of DNA synthesis have been difficult to gather for this organism. 5-ethynyl-2'-deoxyuridine (EdU) is a thymidine analogue that can be incorporated in vivo and later detected using copper-catalyzed azide alkyne cycloaddition (Click reaction) without prior DNA denaturation. This chapter describes a budding yeast strain and conditions that allow rapid EdU incorporation at moderate extracellular concentrations, followed by its efficient detection for the analysis of DNA replication in single cells by flow cytometry and fluorescence microscopy.

  16. Azide-derivatized gold nanosphere "clicked" to indium and zinc phthalocyanines for improved nonlinear optical limiting

    Science.gov (United States)

    Bankole, Owolabi M.; Nyokong, Tebello

    2017-05-01

    We report on the conjugation of azide-derivatized gold nanoparticles (AuNPs) to alkyne moieties of ZnPc and InPc via azide-alkyne Huisgen cycloaddition reaction to form phthalocyanines-AuNPs (MPc-AuNPs) conjugates. The detailed structural characterizations of the composites were in good agreement with the expected results. The nonlinear absorption coefficients and other nonlinear optical limiting parameters were almost two times larger for the conjugates compared to free phthalocyanines. We established direct relationship between improved photophysical characterizations and enhanced nonlinear effects of reverse saturable absorption mechanisms favoured by excited triplet absorption of the phthalocyanines in the presence of AuNPs. The combination of InPc with AuNPs resulted in the lowest limiting intensity value of 0.06 J/cm2, hence the best performance in terms of optical limiting.

  17. Click-to-Chelate: Development of Technetium and Rhenium-Tricarbonyl Labeled Radiopharmaceuticals

    Directory of Open Access Journals (Sweden)

    Thomas L. Mindt

    2013-03-01

    Full Text Available The Click-to-Chelate approach is a highly efficient strategy for the radiolabeling of molecules of medicinal interest with technetium and rhenium-tricarbonyl cores. Reaction of azide-functionalized molecules with alkyne prochelators by the Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC; click reaction enables the simultaneous synthesis and conjugation of tridentate chelating systems for the stable complexation of the radiometals. In many cases, the functionalization of (biomolecules with the ligand system and radiolabeling can be achieved by convenient one-pot procedures. Since its first report in 2006, Click-to-Chelate has been applied to the development of numerous novel radiotracers with promising potential for translation into the clinic. This review summarizes the use of the Click-to-Chelate approach in radiopharmaceutical sciences and provides a perspective for future applications.

  18. The Click Reaction as an Efficient Tool for the Construction of Macrocyclic Structures

    Directory of Open Access Journals (Sweden)

    Dario Pasini

    2013-08-01

    Full Text Available The Cu(I-catalyzed azide-alkyne cycloaddition (CuAAC, known as the click reaction is an established tool used for the construction of complex molecular architectures. Given its efficiency it has been widely applied for bioconjugation, polymer and dendrimer synthesis. More recently, this reaction has been utilized for the efficient formation of rigid or shape-persistent, preorganized macrocyclic species. This strategy also allows the installment of useful functionalities, in the form of polar and function-rich 1,2,3-triazole moieties, directly embedded in the macrocyclic structures. This review analyzes the state of the art in this context, and provides some elements of perspective for future applications.

  19. Computational studies on the regioselectivity of metal-catalyzed synthesis of 1,2,3 triazoles via click reaction: a review.

    Science.gov (United States)

    Hosseinnejad, Tayebeh; Fattahi, Bahareh; Heravi, Majid M

    2015-10-01

    Recently, the experimental and computational chemists have been attracted widely to the click synthesis of 1,2,3 triazoles and their derivatives, mainly due to the fact that they are interesting from structural and mechanistic points of view. Moreover, catalyzed click have been well established as a successful strategy showing high regioselectivity and high yield for the synthesis of 1,2,3-triazoles. In this review, we try to highlight the recently reported computational assessments on the origins and predection of regioselectivity in the catalyzed click synthesis of triazoles from the mechanistic and thermodynamical points of view. In this light, density functional theory (DFT) calculations on the free energy profiles of azide-alkyne cycloaddition reactions have been underscored. The stereoelectronic features for the role of copper, ruthenium, and iridium as catalyst on regioselectivity of click reactions have also be discussed. Graphical Abstract Computational origins for the regioselective behavior of 1,2,3 triazoles click synthesis.

  20. A reação "click" na síntese de 1,2,3-triazóis: aspectos químicos e aplicações

    Directory of Open Access Journals (Sweden)

    Luiza Baptista de Oliveira Freitas

    2011-01-01

    Full Text Available The Copper-catalyzed azide-alkyne cycloaddition (CuAAC, often referred to as "click" reaction, has become a very popular reaction in the last years. It affords exclusively 1,4-disubstituted 1,2,3-triazoles and has been widely used to connect readily accessible building blocks containing various functional groups. The great success of this reaction is based on the fact that it is general, virtually quantitative and very robuste. The scope of this copper-catalyzed synthesis is extraordinary and the reaction has found numerous applications in many research fields, including biological chemistry and materials science. In this review, the main chemical aspects and applications of the "click" reaction in the synthesis of 1,2,3-triazoles are presented.

  1. The cobalt-mediated [2+2+2]cycloaddition of thiophenes and benzofurans to alkynes

    Energy Technology Data Exchange (ETDEWEB)

    Malaska, M.J.

    1991-01-01

    The cobalt-mediated [2+2+2]cycloaddition of thiophenes and benzofurans to alkynes was investigated. The cocyclization of 2-propynyloxymethylthiophenes provided two types of cyclohexadiene complexes. It was found that one of these complexes could be converted to the other by a thermal rearrangement. This novel transformation was investigated by deuterium-labelling and kinetic studies, and a mechanism was proposed. The complexes could be oxidatively demetallated to provide the liberated organic framework. Further reorganization of these dienes were observed during the decomplexation process and in the presence of CpCo(C[sub 2]H[sub 4])[sub 2]. In this manner several new heterocyclic ring systems could be constructed from 2-substituted thiophenes. Following the success of the thiophene cyclizations, the cocyclization of the benzofuran nucleus was examined. Reagents and conditions were developed that provide an efficient synthesis of alkynols from carboxylic acids; other functional group interconversions of the alkynols were briefly studied. The synthesis and cyclization of 1-[7-methoxy-4-benzofuranyl]-3-butyn-2-ol produced a cobalt complex containing the A,B,C, and D rings of the morphine skeleton. A synthetic advantage of this methodology would be the ease of substitution at pharmaco-logically relevant C-6 and C-7 positions of the morphine framework. Synthetic routes using a cobalt cyclization strategy were proposed.

  2. Synthesis of linear and cyclic peptide-PEG-lipids for stabilization and targeting of cationic liposome-DNA complexes.

    Science.gov (United States)

    Ewert, Kai K; Kotamraju, Venkata Ramana; Majzoub, Ramsey N; Steffes, Victoria M; Wonder, Emily A; Teesalu, Tambet; Ruoslahti, Erkki; Safinya, Cyrus R

    2016-03-15

    Because nucleic acids (NAs) have immense potential value as therapeutics, the development of safe and effective synthetic NA vectors continues to attract much attention. In vivo applications of NA vectors require stabilized, nanometer-scale particles, but the commonly used approaches of steric stabilization with a polymer coat (e.g., PEGylation; PEG=poly(ethylene glycol)) interfere with attachment to cells, uptake, and endosomal escape. Conjugation of peptides to PEG-lipids can improve cell attachment and uptake for cationic liposome-DNA (CL-DNA) complexes. We present several synthetic approaches to peptide-PEG-lipids and discuss their merits and drawbacks. A lipid-PEG-amine building block served as the common key intermediate in all synthetic routes. Assembling the entire peptide-PEG-lipid by manual solid phase peptide synthesis (employing a lipid-PEG-carboxylic acid) allowed gram-scale synthesis but is mostly applicable to linear peptides connected via their N-terminus. Conjugation via thiol-maleimide or strain-promoted (copper-free) azide-alkyne cycloaddition chemistry is highly amenable to on-demand preparation of peptide-PEG-lipids, and the appropriate PEG-lipid precursors are available in a single chemical step from the lipid-PEG-amine building block. Azide-alkyne cycloaddition is especially suitable for disulfide-bridged peptides such as iRGD (cyclic CRGDKGPDC). Added at 10 mol% of a cationic/neutral lipid mixture, the peptide-PEG-lipids stabilize the size of CL-DNA complexes. They also affect cell attachment and uptake of nanoparticles in a peptide-dependent manner, thereby providing a platform for preparing stabilized, affinity-targeted CL-DNA nanoparticles.

  3. Click Chemistry and Radiochemistry: The First 10 Years.

    Science.gov (United States)

    Meyer, Jan-Philip; Adumeau, Pierre; Lewis, Jason S; Zeglis, Brian M

    2016-12-21

    The advent of click chemistry has had a profound influence on almost all branches of chemical science. This is particularly true of radiochemistry and the synthesis of agents for positron emission tomography (PET), single photon emission computed tomography (SPECT), and targeted radiotherapy. The selectivity, ease, rapidity, and modularity of click ligations make them nearly ideally suited for the construction of radiotracers, a process that often involves working with biomolecules in aqueous conditions with inexorably decaying radioisotopes. In the following pages, our goal is to provide a broad overview of the first 10 years of research at the intersection of click chemistry and radiochemistry. The discussion will focus on four areas that we believe underscore the critical advantages provided by click chemistry: (i) the use of prosthetic groups for radiolabeling reactions, (ii) the creation of coordination scaffolds for radiometals, (iii) the site-specific radiolabeling of proteins and peptides, and (iv) the development of strategies for in vivo pretargeting. Particular emphasis will be placed on the four most prevalent click reactions-the Cu-catalyzed azide-alkyne cycloaddition (CuAAC), the strain-promoted azide-alkyne cycloaddition (SPAAC), the inverse electron demand Diels-Alder reaction (IEDDA), and the Staudinger ligation-although less well-known click ligations will be discussed as well. Ultimately, it is our hope that this review will not only serve to educate readers but will also act as a springboard, inspiring synthetic chemists and radiochemists alike to harness click chemistry in even more innovative and ambitious ways as we embark upon the second decade of this fruitful collaboration.

  4. Conjugating folate on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles using click chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Xiaofang, E-mail: xfshen@jiangnan.edu.cn; Ge, Zhaoqiang; Pang, Yuehong

    2015-02-15

    Gold-coated magnetic core@shell nanoparticles, which exhibit magneto-optical properties, not only enhance the chemical stability of core and biocompatibility of surface, but also provide a combination of multimodal imaging and therapeutics. The conjugation of these tiny nanoparticles with specific biomolecules allows researchers to target the desired location. In this paper, superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles were synthesized and functionalized with the azide group on the surface by formation of self-assembled monolayers. Folate (FA) molecules, non-immunogenic target ligands for cancer cells, are conjugated with alkyne and then immobilized on the azide-terminated Fe{sub 3}O{sub 4}@Au nanoparticles through copper(I)-catalyzed azide-alkyne cycloaddition (click reaction). Myelogenous leukemia K562 cells were used as a folate receptor (FR) model, which can be targeted and extracted by magnetic field after interaction with the Fe{sub 3}O{sub 4}@Au–FA nanoparticles. - Graphical abstract: Self-assembled azide-terminated group on superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles followed by click reaction with alkyne-functionalized folate, allowing the nanoparticles target folate receptor of cancer cells. - Highlights: • Azidoundecanethiol was coated on the superparamagnetic Fe{sub 3}O{sub 4}@Au nanoparticles by forming self-assembled monolayers. • Alkyne-terminated folate was synthesized from a reaction between the amine and the carboxylic acid. • Conjugation of Fe{sub 3}O{sub 4}@Au nanoparticles with folate was made by copper-catalyzed azide-alkyne cycloaddition click chemistry.

  5. Cicloadições [3+4] via cátions oxialílicos: aplicações em sínteses orgânicas [3+4]Cycloadditions via oxyallyl cations: applications in organic synthesis

    Directory of Open Access Journals (Sweden)

    Antônio Jacinto Demuner

    1997-02-01

    Full Text Available Several methodologies for the generation of oxyallyl cations from polybromoketones and other substrates are discussed. The mechanistic aspect of the [3+4] cycloaddition reaction between these cations and dienes leading to the formation of seven membered ring carbocyclic compounds is presented. Finally, some synthetic applications of the [3+4] cycloaddition are shown.

  6. Highly Regio- and Stereoselective Diels-Alder Cycloadditions via Two-Step and Multicomponent Reactions Promoted by Infrared Irradiation under Solvent-Free Conditions

    Directory of Open Access Journals (Sweden)

    Francisco Delgado

    2012-02-01

    Full Text Available Infrared irradiation promoted the Diels-Alder cycloadditions of exo-2-oxazolidinone dienes 1–3 with the Knoevenagel adducts 4–6, as dienophiles, leading to the synthesis of new 3,5-diphenyltetrahydrobenzo[d]oxazol-2-one derivatives (7, 9, 11 and 13–17, under solvent-free conditions. These cycloadditions were performed with good regio- and stereoselectivity, favoring the para-endo cycloadducts. We also evaluated the one-pot three-component reaction of active methylene compounds 20, benzaldehydes 21 and exo-2-oxazolidinone diene 2 under the same reaction conditions. A cascade Knoevenagel condensation/Diels-Alder cycloaddition reaction was observed, resulting in the final adducts 13–16 in similar yields. These procedures are environmentally benign, because no solvent and no catalyst were employed in these processes. The regioselectivity of these reactions was rationalized by Frontier Molecular Orbital (FMO calculations.

  7. Copper-catalyzed Huisgen 1,3-dipolar cycloaddition under oxidative conditions: polymer-assisted assembly of 4-acyl-1-substituted-1,2,3-triazoles.

    Science.gov (United States)

    Diz, Paula M; Coelho, Alberto; El Maatougui, Abdelaziz; Azuaje, Jhonny; Caamaño, Olga; Gil, Álvaro; Sotelo, Eddy

    2013-07-05

    We herein document the first example of a reliable copper-catalyzed Huisgen 1,3-dipolar cycloaddition under oxidative conditions. The combined use of two polymer-supported reagents (polystyrene-1,5,7-triazabicyclo[4,4,0]dec-5-ene/Cu and polystyrene-2-iodoxybenzamide) overcomes the thermodynamic instability of copper(I) species toward oxidation, enabling the reliable Cu-catalyzed Huisgen 1,3-dipolar cycloadditions in the presence of an oxidant agent. This polymer-assisted pathway, not feasible under conventional homogeneous conditions, provides a direct assembly of 4-acyl-1-substituted-1,2,3-triazoles, contributing to expand the reliability and scope of Cu(I)-catalyzed alkyne-azide cycloaddition.

  8. Benzofurans as efficient dienophiles in normal electron demand [4 + 2] cycloadditions.

    Science.gov (United States)

    Chopin, Nathalie; Gérard, Hélène; Chataigner, Isabelle; Piettre, Serge R

    2009-02-06

    Dearomatization of electron-poor benzofurans is possible through involvement of the aromatic 2,3-carbon-carbon double bond as dienophile in normal electron demand [4 + 2] cycloadditions. The tricyclic heterocycles thereby produced bear a quaternary center at the cis ring junction, a feature of many alkaloids such as morphine, galanthamine, or lunaridine. The products arising from the reaction have been shown to depend on different factors among which the type of the electron-withdrawing substituent of the benzofuran, the nature of the reacting diene, and the method of activation. In the presence of all-carbon dienes, the reaction yields the expected Diels-Alder adducts. When thermal activation is insufficient, a biactivation associating zinc chloride catalysis and high pressure is required to generate the cycloadducts in good yields and high stereoselectivities, for instance, when cyclohexadiene is involved in the process. The use of more functionalized dienes, such as those bearing alkoxy or silyloxy substituents, also shows the limits of the thermal activation, and hyperbaric conditions are, in this case, well-suited. The involvement of Danishefsky's diene induces a competition in the site of reactivity. The aromatic 2,3-carbon-carbon double bond is unambiguously the most reactive dienophile, and the 3-carbonyl unit becomes a competitive site of reactivity with benzofurans bearing substituents prone to heterocyloaddition, in particular under Lewis acid activation. The sequential involvement of both the aromatic double bond and the carbonyl moiety as dienophiles is then possible by using an excess of diene under high-pressure activation. In line with the experimental results, DFT computations suggest that the Diels-Alder process involving the aromatic double bond is preferred over the hetero-Diels-Alder route through an asynchronous concerted transition state. However, Lewis acid catalysis appears to favor the heterocycloaddition pathway through a stepwise

  9. Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

    Directory of Open Access Journals (Sweden)

    Regina Berg

    2013-12-01

    Full Text Available The copper-catalyzed azide–alkyne cycloaddition (CuAAC is one of the most broadly applicable and easy-to-handle reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species itself has remained subject to speculation, which can be attributed to the multifaceted aggregation chemistry of copper(I alkyne and acetylide complexes. Following an introductory section on common catalyst systems in CuAAC reactions, this review will highlight experimental and computational studies from early proposals to very recent and more sophisticated investigations, which deliver more detailed insights into the CuAAC’s catalytic cycle and the species involved. As diverging mechanistic views are presented in articles, books and online resources, we intend to present the research efforts in this field during the past decade and finally give an up-to-date picture of the currently accepted dinuclear mechanism of CuAAC. Additionally, we hope to inspire research efforts on the development of molecularly defined copper(I catalysts with defined structural characteristics, whose main advantage in contrast to the regularly used precatalyst reagent mixtures is twofold: on the one hand, the characteristics of molecularly defined, well soluble catalysts can be tuned according to the particular requirements of the experiment; on the other hand, the understanding of the CuAAC reaction mechanism can be further advanced by kinetic studies and the isolation and characterization of key intermediates.

  10. CO2 Conversion: The Potential of Porous–Organic Polymers (POPs) for the cycloaddition of CO2 and epoxides

    KAUST Repository

    Alkordi, Mohamed Helmi

    2016-03-30

    Novel porous organic polymers (POPs) have been synthesized using functionalized Cr and Co-salen complexes as molecular building blocks. The integration of metalosalen catalysts into the porous polymers backbone permits the successful utilization of the materials as solid-state catalysts for CO2-epoxide cycloadditions reactions with excellent catalytic performance under mild conditions of temperature and pressure. The catalyst proved to be fully recyclable and robust thus showing the potential of POPs as smart functional materials for the heterogenization of key catalytic elements.

  11. A modular approach for the construction and modification of glyco-SAMs utilizing 1,3-dipolar cycloaddition.

    Science.gov (United States)

    Kleinert, Mike; Winkler, Tobias; Terfort, Andreas; Lindhorst, Thisbe K

    2008-06-21

    We report the synthesis of a broad variety of functionalized molecules for assembly on gold, allowing the formation of biologically relevant SAMs by a modular approach: either utilizing 1,3-dipolar cycloaddition of alkynes and azides in solution or by 'click on SAM'. Extensive studies into the various parameters of SAM formation and stability have been carried out, leading us to deduce reliable conditions under which glyco-decorated self-assembled monolayers can be formed and studied such as in SPR-supported binding assays.

  12. Synthesis of indazoles by the [3+2] cycloaddition of diazo compounds with arynes and subsequent acyl migration.

    Science.gov (United States)

    Liu, Zhijian; Shi, Feng; Martinez, Pablo D G; Raminelli, Cristiano; Larock, Richard C

    2008-01-04

    The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions. Simple diazomethane derivatives afford N-unsubstituted indazoles or 1-arylated indazoles, depending upon the stoichiometry of the reagents and the reaction conditions, while dicarbonyl-containing diazo compounds undergo carbonyl migration to afford 1-acyl or 1-alkoxycarbonyl indazoles selectively.

  13. Sequential One-Pot Ruthenium-Catalyzed Azide−Alkyne Cycloaddition from Primary Alkyl Halides and Sodium Azide

    KAUST Repository

    Johansson, Johan R.

    2011-04-01

    An experimentally simple sequential one-pot RuAAC reaction, affording 1,5-disubstituted 1H-1,2,3-triazoles in good to excellent yields starting from an alkyl halide, sodium azide, and an alkyne, is reported. The organic azide is formed in situ by treating the primary alkyl halide with sodium azide in DMA under microwave heating. Subsequent addition of [RuClCp*(PPh 3) 2] and the alkyne yielded the desired cycloaddition product after further microwave irradiation. © 2011 American Chemical Society.

  14. Enantioselective Synthesis of N-PMP-1,2-dihydropyridines via Formal [4 + 2] Cycloaddition between Aqueous Glutaraldehyde and Imines.

    Science.gov (United States)

    Ramaraju, Panduga; Mir, Nisar A; Singh, Deepika; Gupta, Vivek K; Kant, Rajni; Kumar, Indresh

    2015-11-20

    A simple and highly practical one-pot formal [4 + 2] cycloaddition approach for the enantioselective synthesis of N-PMP-1,2-dihydropyridines (DHPs) is described. This chemistry involves an amino-catalytic direct Mannich reaction/cyclization followed by IBX-mediated chemo- and regioselective oxidation sequence between readily available aqueous glutaraldehyde and imines under very mild conditions. A series of N-PMP-1,2-DHPs have been prepared in high yields and excellent enantioselectivity. This method also gives access to both enantiomers of 1,2-DHPs in surplus amount by shifting the catalyst configuration.

  15. End-labeled amino terminated monotelechelic glycopolymers generated by ROMP and Cu(I-catalyzed azide–alkyne cycloaddition

    Directory of Open Access Journals (Sweden)

    Ronald Okoth

    2013-03-01

    Full Text Available Functionalizable monotelechelic polymers are useful materials for chemical biology and materials science. We report here the synthesis of a capping agent that can be used to terminate polymers prepared by ring-opening metathesis polymerization of norbornenes bearing an activated ester. The terminating agent is a cis-butene derivative bearing a Teoc (2-trimethylsilylethyl carbamate protected primary amine. Post-polymerization modification of the polymer was accomplished by amidation with an azido-amine linker followed by Cu(I-catalyzed azide–alkyne cycloaddition with propargyl sugars. Subsequent Teoc deprotection and conjugation with pyrenyl isothiocyanates afforded well-defined end-labeled glycopolymers.

  16. Tricyclohexylphosphine-Catalyzed Cycloaddition of Enynoates with [60]Fullerene and the Application of Cyclopentenofullerenes as n-Type Materials in Organic Photovoltaics.

    Science.gov (United States)

    Wu, An-Ju; Tseng, Po-Yen; Hsu, Wei-Hsin; Chuang, Shih-Ching

    2016-01-15

    The tricyclohexylphosphine-catalyzed [3 + 2] cycloaddition of (E)-alkyl 5-substituted phenylpent-4-en-2-ynoates with [60]fullerene was studied. This reaction undergoes an initial 1,3-addition of phosphines toward the α-carbons of enynoates. Subsequent cycloaddition of the generated 1,3-dipoles with [60]fullerene and elimination of tricyclohexylphosphines resulted in cyclopentenofullerenes in 20-43% yields. The isolated cyclopentenofullerenes were observed to serve as n-type materials in organic photovoltaics, providing a maximum average power conversion efficiency of 3.79 ± 0.29% upon embedding with P3HT in the active layer.

  17. Parallel Synthesis of Tetraaryl-4,5-dihydro-1,2,4-triazoles via 1,3-Dipolar Cycloaddition on Soluble Polymer Support

    Institute of Scientific and Technical Information of China (English)

    SHOU,Wang-Ge; WANG,Yan-Guang

    2004-01-01

    @@ The polymer-supported liquid-phase synthesis of small organic molecules has been a subject of intense research activity. 1,2,4-Triazoles are well known for their antifungal[1] and antibacterial[2] activities. This moiety was also found in potent agonist or antagonist receptor lingands. The synthesis of substituted 1,2,4-triazoles via 1,3-dipolar cycloaddition of imines with nitrilimines is well documented.[3] Herein, we would like to report the first liquid-phase synthesis of 1,3,4,5-tetraaryl-4,5-dihydro-1,2,4-triazoles through a 1,3-dipolar cycloaddition of imines with nitrilimines on PEG support.

  18. Efficient microwave assisted synthesis of novel 1,2,3-triazole-sucrose derivatives by cycloaddition reaction of sucrose azides and terminal alkynes.

    Science.gov (United States)

    Potewar, Taterao M; Petrova, Krasimira T; Barros, M Teresa

    2013-09-20

    Novel 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-substituted-1,2,3-triazoles were synthesized by microwave assisted copper catalyzed 1,3-dipolar cycloaddition of sucrose derived azides with terminal alkynes in excellent yields and in short reaction times. The compound 1',2,3,3',4,4',6-hepta-O-acetyl-6'-azido-6'-deoxy-sucrose was regioselectively synthesized from sucrose by improved procedure and used for the cycloadditions. By combining carbohydrate and 1,2,3-triazole structural motifs, a library of 1,2,3-triazole-sucrose conjugates have been obtained.

  19. Diastereoselective synthesis of potent antimalarial cis-β-lactam agents through a [2 + 2] cycloaddition of chiral imines with a chiral ketene.

    Science.gov (United States)

    Jarrahpour, Aliasghar; Ebrahimi, Edris; Sinou, Véronique; Latour, Christine; Brunel, Jean Michel

    2014-11-24

    The effect of double asymmetric induction for the synthesis of new cis-β-lactams by [2 + 2] cycloaddition reactions of chiral imines with a chiral ketene was investigated. The cycloaddition reaction was found to be totally diastereoselective leading exclusively to the formation of the cis-β-lactam derivatives. The newly synthesized cycloadducts were evaluated for their antimalarial activities against Plasmodium falciparum K14 resistant strain with moderate to excellent IC50 values varying from 8 to 50 μM. Of the fifteen β-lactams tested, four showed IC50 ≤ 11 μM. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Total facial selectivity of a D-erythrosyl aromatic imine in [4π + 2π] cycloadditions; synthesis of 2-alkylpolyol 1,2,3,4-tetrahydroquinolines.

    Science.gov (United States)

    Ferreira, Juliana; Duarte, Vera C M; Noro, Jennifer; Gil Fortes, António; Alves, Maria J

    2016-03-14

    Different electron-rich dienophiles were combined with the imine obtained from 2,4-O-benzylidene-d-erythrose and p-anisidine furnishing enantiomerically pure tetrahydroquinolines, by inverse electron-demand [4π + 2π] cycloaddition. The imine was also reacted with 2-substituted electron-rich 1,3-butadienes giving the diastereomeric pure product, resulting from the normal electron demand cycloaddition. The facial selectivity of both processes is proposed on the basis of a 1,4-relationship between the hydroxyl group and the nitrogen atom in the chiral N-(p-methoxyphenyl)imine derivative.

  1. A Cycloaddition Strategy for Use toward Berkelic Acid, an MMP Inhibitor and Potent Anticancer Agent Displaying a Unique Chroman Spiroketal Motif.

    Science.gov (United States)

    Huang, Yaodong; Pettus, Thomas R R

    2008-05-11

    A kinetically controlled diastereoselective cycloaddition between a chiral enol ether and an ortho-quinone methide (o-QM) produces a chroman spiroketal motif that is found in the core of berkelic acid, a novel matrix metalloproteinase (MMP) inhibitor and potent anticancer agent. The transformation lays the groundwork for preparation of future inhibitors aimed at distinguishing among the active sites of the twenty-three known MMP. Experimental findings suggest that the stereochemistry that emerges from cycloaddition is opposite that which results from thermodynamic ketalization.

  2. Cobalt-Catalyzed [2π + 2π] Cycloadditions of Alkenes: Scope, Mechanism, and Elucidation of Electronic Structure of Catalytic Intermediates.

    Science.gov (United States)

    Schmidt, Valerie A; Hoyt, Jordan M; Margulieux, Grant W; Chirik, Paul J

    2015-06-24

    Aryl-substituted bis(imino)pyridine cobalt dinitrogen compounds, ((R)PDI)CoN2, are effective precatalysts for the intramolecular [2π + 2π] cycloaddition of α,ω-dienes to yield the corresponding bicyclo[3.2.0]heptane derivatives. The reactions proceed under mild thermal conditions with unactivated alkenes, tolerating both amine and ether functional groups. The overall second order rate law for the reaction, first order with respect to both the cobalt precatalyst and the substrate, in combination with electron paramagnetic resonance (EPR) spectroscopic studies established the catalyst resting state as dependent on the identity of the precatalyst and diene substrate. Planar S = ½ κ(3)-bis(imino)pyridine cobalt alkene and tetrahedral κ(2)-bis(imino)pyridine cobalt diene complexes were observed by EPR spectroscopy and in the latter case structurally characterized. The hemilabile chelate facilitates conversion of a principally ligand-based singly occupied molecular orbital (SOMO) in the cobalt dinitrogen and alkene compounds to a metal-based SOMO in the diene intermediates, promoting C-C bond-forming oxidative cyclization. Structure-activity relationships on bis(imino)pyridine substitution were also established with 2,4,6-tricyclopentyl-substituted aryl groups, resulting in optimized catalytic [2π + 2π] cycloaddition. The cyclopentyl groups provide a sufficiently open metal coordination sphere that encourages substrate coordination while remaining large enough to promote a challenging, turnover-limiting C(sp(3))-C(sp(3)) reductive elimination.

  3. SPECTRAL AND CHEMICAL MONITORING OF CYCLO-ADDITION REACTION OF CO2 WITH POLY(MMA-co-GMA) COPOLYMERS

    Institute of Scientific and Technical Information of China (English)

    M.Yadollahi; H.Bouhendi; M.J.Zohuriaan-Mehr; K.Kabiri

    2012-01-01

    This paper deals with the monitoring cyclo-addition of CO2 to methyl methacrylate (MMA)-glycidyl methacrylate (GMA) copolymers using spectral (1H-NMR and FTIR) and chemical (elemental analysis and titration) methods.Thus,poly(MMA-co-GMA),was first prepared via solution polymerization.The copolymer was then treated with CO2 gas flow in the presence of cetyltrimethyl ammoniumbromide as a catalyst.In terms of the carbonation reaction time,the terpolymer poly(MMA-co-GMA-co-2-oxo-l,3-dioxolane-4-yl-methyl methacrylate) was prepared in various yield of CO2 fixation (> 90%).The peak intensity changes in the 1H-NMR and FTIR spectra provided excellent demonstrative techniques to monitor the carbonation reaction progression.In a comparative analytical viewpoint,the NMR and elemental analysis were recognized to be the most accurate ways to follow the cyclo-addition reaction progression.However,titration was recognized to be the most preferred method,because it is a very inexpensive,facile and available method with a reasonable costaccuracy balance.

  4. Adhesion of Photon-Driven Molecular Motors to Surfaces via 1,3-Dipolar Cycloadditions : Effect of Interfacial Interactions on Molecular Motion

    NARCIS (Netherlands)

    Carroll, Gregory T.; London, Gabor; Fernández Landaluce, Tatiana; Rudolf, Petra; Feringa, Ben L.

    2011-01-01

    We report the attachment of altitudinal light-driven molecular motors to surfaces using 1,3-dipolar cycloaddition reactions. Molecular motors were designed containing azide or alkyne groups for attachment to alkyne- or azide-modified surfaces. Surface attachment was characterized by UV-vis, IR, XPS,

  5. Synthesis of [F-18]RGD-K5 by catalyzed [3+2] cycloaddition for imaging integrin alpha(v)beta(3) expression in vivo

    NARCIS (Netherlands)

    Mirfeizi, Leila; Walsh, Joe; Kolb, Hartmuth; Campbell-Verduyn, Lachlan; Dierckx, Rudi A.; Feringa, Ben L.; Elsinga, Philip H.; de Groot, Tjibbe; Sannen, Ivan; Bormans, Guy; Celen, Sofie

    2013-01-01

    In the last few years click chemistry reactions, and in particular copper-catalyzed cycloadditions have been used extensively for the preparation of new bioconjugated molecules such as F-18-radiolabeled radiopharmaceuticals for positron emission tomography (PET). This study is focused on the synthes

  6. Synthesis of isofagomine-pyrrolidine hybrid sugars and analogues of (-)-steviamine and (+)-hyacinthacine C5 using 1,3-dipolar cycloaddition reactions.

    Science.gov (United States)

    Lahiri, Rima; Palanivel, Ashokkumar; Kulkarni, Sudhir A; Vankar, Yashwant D

    2014-11-21

    Highly regioselective 1,3-dipolar cycloadditions between d-arabinose-derived nitrones and d-mannitol-derived trans-olefins have been utilized to synthesize isofagomine-pyrrolidine hybrid sugars, hydroxymethylated analogues of (-)-steviamine and analogues of (+)-hyacinthacine C5. All of the new compounds were subsequently tested against several commercially available glycosidases, and some of them showed good and selective glycosidase inhibition.

  7. Regioselective [2 + 2] cycloaddition of a fullerene dimer with an alkyne triggered by thermolysis of an interfullerene C-C bond.

    Science.gov (United States)

    Xiao, Zuo; Matsuo, Yutaka; Maruyama, Masashi; Nakamura, Eiichi

    2013-05-03

    Heating of a singly bonded fullerene dimer in the presence of an alkyne forms a cyclobutene structure on only one of the two fullerene moieties, through a stereo- and regioselective [2 + 2] cycloaddition. Experimental and theoretical data suggest that the reaction is triggered by cleavage of the interfullerene C-C bond and formation of a monomeric fullerene radical.

  8. New synthesis of 1-substituted-1H-indazoles via 1,3-dipolar cycloaddition of in situ generated nitrile imines and benzyne.

    Science.gov (United States)

    Spiteri, Christian; Keeling, Steve; Moses, John E

    2010-08-06

    A new synthesis of 1-substituted-1H-indazoles via 1,3-dipolar cycloaddition of nitrile imines to benzyne is described. The reaction is completed within 5 min, affording the corresponding N(1)-C(3) disubstituted indazoles in moderate to excellent yields.

  9. One-pot synthesis of new series 3,4,5-trisubstituted-dihydroisoxazoline derivatives via 1,3-dipolar cycloaddition of nitrile oxides with chalcones

    Indian Academy of Sciences (India)

    Raad Kasim Yhya; K M Lokanatha Rai; Ebraheem Abdu Musad

    2013-07-01

    We have synthesized a series of novel isoxazolines via 1,3-dipolar cycloaddition reaction. Aromatic aldoximes undergo oxidative-dehydrogenation with chloramine-T to give nitrile oxides, which were reacted with chalcones to afford of 3,4,5-trisubstituted 4,5-dihydroisoxazolines in a good yield.

  10. A highly active and reusable copper(I)-tren catalyst for the "click" 1,3-dipolar cycloaddition of azides and alkynes.

    Science.gov (United States)

    Candelon, Nicolas; Lastécouères, Dominique; Diallo, Abdou Khadri; Aranzaes, Jaime Ruiz; Astruc, Didier; Vincent, Jean-Marc

    2008-02-14

    The copper(I) complex [Cu(C18(6)tren)]Br 1 (C18(6)tren = tris(2-dioctadecylaminoethyl)amine) which exhibits a good stability towards aerobic conditions is a versatile, highly reactive and recyclable catalyst for the Huisgen cycloaddition of azides with terminal or internal alkynes and is a useful catalyst for the preparation of "click" dendrimers.

  11. Improved Synthesis of 5-Substituted 1H-Tetrazoles via the [3+2] Cycloaddition of Nitriles and Sodium Azide Catalyzed by Silica Sulfuric Acid

    Science.gov (United States)

    Du, Zhenting; Si, Changmei; Li, Youqiang; Wang, Yin; Lu, Jing

    2012-01-01

    A silica supported sulfuric acid catalyzed [3+2] cycloaddition of nitriles and sodium azide to form 5-substituted 1H-tetrazoles is described. The protocol can provide a series of 5-substituted 1H-tetrazoles using silica sulfuric acid from nitriles and sodium azide in DMF in 72%–95% yield. PMID:22606004

  12. Improved Synthesis of 5-Substituted 1H-Tetrazoles via the [3+2] Cycloaddition of Nitriles and Sodium Azide Catalyzed by Silica Sulfuric Acid

    Directory of Open Access Journals (Sweden)

    Jing Lu

    2012-04-01

    Full Text Available A silica supported sulfuric acid catalyzed [3+2] cycloaddition of nitriles and sodium azide to form 5-substituted 1H-tetrazoles is described. The protocol can provide a series of 5-substituted 1H-tetrazoles using silica sulfuric acid from nitriles and sodium azide in DMF in 72%–95% yield.

  13. In-depth evaluation of the cycloaddition--retro-Diels--Alder reaction for in vivo targeting with [(111)In]-DTPA-RGD conjugates.

    NARCIS (Netherlands)

    Laverman, P.; Meeuwissen, S.A.; Berkel, S.S. van; Oyen, W.J.G.; Delft, F.L. van; Rutjes, F.P.J.T.; Boerman, O.C.

    2009-01-01

    INTRODUCTION: The spontaneous copper-free tandem 1,3-dipolar cycloaddition-retro-Diels-Alder (tandem crDA) reaction between cyclic Arg-Gly-Asp-d-Phe-Orn(N(3)) [c(RGDfX)] and oxanorbornadiene-DTPA (o-DTPA) or methyloxanorbornadiene-DTPA (mo-DTPA) into two DTPA-c(RGDfX) regioisomers is characterized.

  14. Rapid access to spirocylic oxindoles: application of asymmetric N-heterocyclic carbene-catalyzed [3 + 3] cycloaddition of imines to oxindole-derived enals.

    Science.gov (United States)

    Xie, Danbo; Yang, Limin; Lin, Youqiang; Zhang, Zhiming; Chen, Dongdong; Zeng, Xiaofei; Zhong, Guofu

    2015-05-15

    A chiral N-heterocyclic carbene (NHC)-catalyzed [3 + 3] cycloaddition reaction of imines and oxindole-derived enals was developed for rapid access to spirocylic oxindoles. In most cases, the desired spirocylic oxindole products were obtained in high yields and excellent enantioselectivities with less than 1 h of reaction time.

  15. Understanding the domino retro [3+2] cycloaddition/cyclization reaction of bicyclic isoxazolidines in the synthesis of spirocyclic alkaloids. A DFT study.

    Science.gov (United States)

    Layeb, Hatem; Nacereddine, Abdelmalek Khorief; Djerourou, Abdelhafid; Domingo, Luis R

    2014-07-01

    The domino retro [3+2] cycloaddition/cyclization reaction of bicyclic isoxazolidines 4 yielding [6.6.5]-tricyclic isoxazolidines 7 and [6.5.5]-tricyclic isoxazolidines 8, experimentally reported by Holmes et al., has been studied in toluene using DFT methods at the MPWB1K/6-311G** level. This domino reaction begins by a reto [3+2] cycloaddition reaction of the bicyclic isoxazolidines 4 forming the cyclic nitrones 5, which undergo a subsequent cyclization reaction yielding [6.6.5]-tricyclic isoxazolidines 7 or [6.5.5]-tricyclic isoxazolidines 8. The [3+2] cycloaddition reactions of cyclic nitrone 12 with ethylene 13, and with (Z)-but-2-enenitrile 15 were also studied in order to explain the role of the tether in the cyclization step. The present study shows that, unlike the [3+2] cycloaddition reaction of cyanoalkene 15, the cyano group in the cyclization step does not have any effect on the selectivity. The present study suggests that the presence of the BF3 catalyst in the domino reaction can change the formation of the [6.5.5]-tricyclic isoxazolidine 7 to the [6.6.5]-tricyclic isoxazolidine 8.

  16. Total synthesis of gracilioether F. Development and application of Lewis acid promoted ketene–alkene [2+2] cycloadditions and late-stage C—H oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Rasik, Christopher M. [Indiana Univ., Bloomington, IN (United States); Brown, M. Kevin [Indiana Univ., Bloomington, IN (United States)

    2014-12-22

    The first synthesis of gracilioether F, a polyketide natural product with an unusual tricyclic core and five contiguous stereocenters, is described. Key steps of the synthesis include a Lewis acid promoted ketene–alkene [2+2] cycloaddition and a late-stage carboxylic acid directed C(sp³)—H oxidation. The synthesis requires only eight steps from norbornadiene.

  17. A Straightforward Route to Enantiopure Pyrrolizidines and Indolizidines by Cycloaddition to Pyrroline N-Oxides Derived from the Chiral Pool

    Directory of Open Access Journals (Sweden)

    Alberto Brandi

    1998-12-01

    Full Text Available Enantiomerically pure, five membered cyclic nitrones, easily obtained in large amounts from protected hydroxyacids and aminoacids such as D- and L-tartaric, L-malic, and L-aspartic acids, give cycloaddition reactions with a good diastereocontrol. The adducts of L-malic and L-aspartic acids derived from addition of nitrones to dimethyl maleate and g-crotonolactone were easily converted into enantiopure pyrrolizidinones, which can be transformed into polyhydroxypyrrolidines or polyhydroxypyrrolizidines, both interesting compounds as potential glycosidase inhibitors. The method is suitable for natural products synthesis as exemplified by a straightforward and convenient access to the pyrrolizidine alkaloid necine base (–-hastanecine, as well as to indolizidine alkaloids, i.e. (+- lentiginosine.

  18. The chemistry of simple alkene molecules on Si(100)c(4 × 2): The mechanism of cycloaddition and their selectivities

    Science.gov (United States)

    Akagi, Kazuto; Yoshinobu, Jun

    2016-10-01

    The chemistry of simple alkene molecules on the Si(100) surface is reviewed with the newly-produced visual presentation by theoretical calculations. The early pioneering studies by the Kyoto Group and Pittsburgh group reported the di-σ bond formation and the precursor-mediated chemisorption for acetylene and ethylene on Si(100), respectively. Thereafter, these studies have been stimulating various studies of organic molecules on Si surfaces. Our recent studies have observed the precursor states for alkene chemisorption and elucidated the microscopic mechanisms of the di-σ bond formation (cycloaddition) with the help of theoretical calculations; the site-, stereo- and regio-selective chemisorption of simple alkene molecules on Si(100)c(4 × 2) has been established.

  19. Synthesis with Perfect Atom Economy: Generation of Furan Derivatives by 1,3-Dipolar Cycloaddition of Acetylenedicarboxylates at Cyclooctynes

    Directory of Open Access Journals (Sweden)

    Klaus Banert

    2014-09-01

    Full Text Available Cyclooctyne and cycloocten-5-yne undergo, at room temperature, a 1,3-dipolar cycloaddition with dialkyl acetylenedicarboxylates 1a,b to generate furan-derived short-lived intermediates 2, which can be trapped by two additional equivalents of 1a,b or alternatively by methanol, phenol, water or aldehydes to yield polycyclic products 3b–d, orthoesters 4a–c, ketones 5 or epoxides 6a,b, respectively. Treatment of bis(trimethylsilyl acetylenedicarboxylate (1c with cyclooctyne leads to the ketone 7 via retro-Brook rearrangement of the dipolar intermediate 2c. In all cases, the products are formed with perfect atom economy.

  20. Donor/Acceptor-Stabilized 1-Silaketene: Reversible [2+2] Cycloaddition with Pyridine and Evolution by an Olefin Metathesis Reaction.

    Science.gov (United States)

    Reyes, Morelia Lopez; Troadec, Thibault; Rodriguez, Ricardo; Baceiredo, Antoine; Saffon-Merceron, Nathalie; Branchadell, Vicenç; Kato, Tsuyoshi

    2016-07-11

    The reaction of silacyclopropylidene 1 with benzaldehyde generates a 1-silaketene complex 2 by a formal atomic silicon insertion into the C=O bond of the aldehyde. The highly reactive 1-silaketene 2 undergoes a reversible [2+2] cycloaddition with pyridine to give sila-β-lactam 3. Of particular interest, in the presence of 4-dimethylaminopyridine (DMAP), 1-silaketene complex 2 evolves through an intramolecular olefin metathesis reaction, generating a new 1-silaketene complex 8 and cis-stilbene. Theoretical studies suggest that the reaction proceeds through the formation of a transient silacyclobutanone, a four-membered-ring intermediate, similar to that proposed by Chauvin and co-workers for the transition-metal-based olefin metathesis.

  1. The 1,3-dipolar cycloaddition reaction of chiral carbohydrate-derived nitrone and olefin: towards long-chain sugars.

    Science.gov (United States)

    Oukani, Hassan; Pellegrini-Moïse, Nadia; Jackowski, Olivier; Chrétien, Françoise; Chapleur, Yves

    2013-11-15

    The thermal and microwave-activated 1,3-dipolar cycloadditions of several α,β-unsaturated esters derived from d-mannose and chiral nitrones derived from threitol have been studied as a model reaction en route to eleven carbon long chain carbohydrates. Very high facial selectivity is observed for the chiral nitrones whereas the olefin facial selectivity varies with the substrate. The presence of a dioxolane ring α to the olefinic bond is beneficial to the facial selectivity of the olefin whereas a pyranose ring is not. The combination of a d-mannose derivative and a l-threitol-derived nitrone is a matched pair suitable for the synthesis of long chain sugars with nine contiguous chiral centres. Finally complete facial selectivity was observed with exo-glycals which gave a single cycloadduct.

  2. Ligand-enabled multiple absolute stereocontrol in metal-catalysed cycloaddition for construction of contiguous all-carbon quaternary stereocentres.

    Science.gov (United States)

    Ohmatsu, Kohsuke; Imagawa, Naomichi; Ooi, Takashi

    2014-01-01

    The development of a general catalytic method for the direct and stereoselective construction of contiguous all-carbon quaternary stereocentres remains a formidable challenge in chemical synthesis. Here, we report a highly enantio- and diastereoselective [3+2] annulation reaction of 5-vinyloxazolidinones and activated trisubstituted alkenes catalysed by a palladium complex bearing a newly devised phosphine ligand with a chiral ammonium salt component, which enables the single-step construction of three contiguous stereocentres, including vicinal all-carbon quaternary stereocentres, in a five-membered heterocyclic framework. This stereoselective cycloaddition protocol relies on the remarkable ability of the chiral ligand to rigorously control the absolute stereochemistry of each chiral centre associated with the multiple bond-forming events, and provides a reliable catalytic process for the asymmetric synthesis of densely functionalized pyrrolidines.

  3. Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(i) acetylides†

    Science.gov (United States)

    Hein, Jason E.

    2011-01-01

    Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(i) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science. PMID:20309487

  4. Chemical reactivity in nucleophilic cycloaddition to C70: vibronic coupling density and vibronic coupling constants as reactivity indices.

    Science.gov (United States)

    Haruta, Naoki; Sato, Tohru; Tanaka, Kazuyoshi

    2012-11-02

    The chemical reactivity in nucleophilic cycloaddition to C70 is investigated on the basis of vibronic (electron-vibration) coupling density and vibronic coupling constants. Because the e1″ LUMOs of C70 are doubly degenerate and delocalized throughout the molecule, it is difficult to predict the regioselectivity by frontier orbital theory. It is found that vibronic coupling density analysis for the effective mode as a reaction mode illustrates the idea of a functional group embedded in the reactive sites. Furthermore, the vibronic coupling constants for localized stretching vibrational modes enable us to estimate the quantitative reactivity. These calculated results agree well with the experimental findings. The principle of chemical reactivity proposed by Parr and Yang is modified as follows: the preferred direction is the one for which the initial vibronic coupling density for a reaction mode of the isolated reactant is a minimum.

  5. Aprotic Heterocyclic Anion Triazolide Ionic Liquids - A New Class of Ionic Liquid Anion Accessed by the Huisgen Cycloaddition Reaction

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, Robert [National Energy Technology Laboratory; Damodaran, Krishnan [Department of Chemistry, University of Pittsburgh; Luebke, David [National Energy Technology Laboratory; Nulwala, Hunaid [National Energy Technology Laboratory

    2013-04-18

    The triazole core is a highly versatile heterocyclic ring which can be accessed easily with the Cu(I)-catalyzed Huisgen cycloaddition reaction. Herein we present the preparation of ionic liquids that incorporate a 1,2,3-triazolide anion. These ionic liquids were prepared by a facile procedure utilizing a base-labile pivaloylmethyl group at the 1-position, which can act as precursors to 1H- 4-substituted 1,2,3-triazole. These triazoles were then subsequently converted into ionic liquids after deprotonation using an appropriate ionic liquid cation hydroxide. The densities and thermal decompositions of these ionic liquids were measured. These novel ionic liquids have potential applications in gas separations and in metal-free catalysis.

  6. Regioselective Synthesis of C-3-Functionalized Quinolines via Hetero-Diels-Alder Cycloaddition of Azadienes with Terminal Alkynes.

    Science.gov (United States)

    Saunthwal, Rakesh K; Patel, Monika; Verma, Akhilesh K

    2016-08-05

    A highly efficient metal and protection-free approach for the regioselective synthesis of C-3-functionalized quinolines from azadienes (in situ generated from 2-aminobenzyl alcohol) and terminal alkynes through [4 + 2] cycloaddition has been developed. An unprecedented reaction of 2-aminobenzyl alcohol with 1,3- and 1,4-diethynylbenzene provided the C-3 tolylquinolines via [4 + 2] HDA and oxidative decarboxylation. The -NH2 group directed mechanistic approach was well supported by the control experiments and deuterium-labeling studies and by isolating the azadiene intermediate. The reactivity and selectivity of unprotected azadiene in metal-free base-assisted hetero-Diels-Alder reaction is exploited to quickly assemble an important class of C-3-functionalized quinolines, which are difficult to access.

  7. Discovery of TNF inhibitors from a DNA-encoded chemical library based on diels-alder cycloaddition.

    Science.gov (United States)

    Buller, Fabian; Zhang, Yixin; Scheuermann, Jörg; Schäfer, Juliane; Bühlmann, Peter; Neri, Dario

    2009-10-30

    DNA-encoded chemical libraries are promising tools for the discovery of ligands toward protein targets of pharmaceutical relevance. DNA-encoded small molecules can be enriched in affinity-based selections and their unique DNA "barcode" allows the amplification and identification by high-throughput sequencing. We describe selection experiments using a DNA-encoded 4000-compound library generated by Diels-Alder cycloadditions. High-throughput sequencing enabled the identification and relative quantification of library members before and after selection. Sequence enrichment profiles corresponding to the "bar-coded" library members were validated by affinity measurements of single compounds. We were able to affinity mature trypsin inhibitors and identify a series of albumin binders for the conjugation of pharmaceuticals. Furthermore, we discovered a ligand for the antiapoptotic Bcl-xL protein and a class of tumor necrosis factor (TNF) binders that completely inhibited TNF-mediated killing of L-M fibroblasts in vitro.

  8. Covalently crosslinked diels-alder polymer networks.

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, Christopher (University of Colorado, Boulder, CO); Adzima, Brian J. (University of Colorado, Boulder, CO); Anderson, Benjamin John

    2011-09-01

    This project examines the utility of cycloaddition reactions for the synthesis of polymer networks. Cycloaddition reactions are desirable because they produce no unwanted side reactions or small molecules, allowing for the formation of high molecular weight species and glassy crosslinked networks. Both the Diels-Alder reaction and the copper-catalyzed azide-alkyne cycloaddition (CuAAC) were studied. Accomplishments include externally triggered healing of a thermoreversible covalent network via self-limited hysteresis heating, the creation of Diels-Alder based photoresists, and the successful photochemical catalysis of CuAAC as an alternative to the use of ascorbic acid for the generation of Cu(I) in click reactions. An analysis of the results reveals that these new methods offer the promise of efficiently creating robust, high molecular weight species and delicate three dimensional structures that incorporate chemical functionality in the patterned material. This work was performed under a Strategic Partnerships LDRD during FY10 and FY11 as part of a Sandia National Laboratories/University of Colorado-Boulder Excellence in Science and Engineering Fellowship awarded to Brian J. Adzima, a graduate student at UC-Boulder. Benjamin J. Anderson (Org. 1833) was the Sandia National Laboratories point-of-contact for this fellowship.

  9. Imino [4+4] cycloaddition products as exclusive and biologically relevant acrolein-amine conjugates are intermediates of 3-formyl-3,4-dehydropiperidine (FDP), an acrolein biomarker.

    Science.gov (United States)

    Takamatsu, Masayuki; Fukase, Koichi; Kurbangalieva, Almira; Tanaka, Katsunori

    2014-11-15

    We demonstrated synthetically that the eight-membered heterocycles 2,6,9-triazabicyclo[3.3.1]nonanes and 1,5-diazacyclooctanes are the initial and exclusive products of the reaction, through an imino [4+4] cycloaddition, of biologically relevant amines with acrolein. The stabilities of the aminoacetals within the eight-membered heterocycles determined whether the product was subsequently transformed gradually into the 3-formyl-3,4-dehydropiperidine (FDP), which is widely used as an oxidative stress marker. The reactivity profiles discovered in this study suggested that some of the imino [4+4] cycloaddition products are reactive intermediates of FDP and contribute to the mechanisms underlying the oxidative stress response to acrolein.

  10. Mechanism and regioselectivity of 1,3-dipolar cycloaddition reactions of sulphur-centred dipoles with furan-2,3-dione: A theoretical study using DFT

    Indian Academy of Sciences (India)

    Saeed Reza Emamian; Safa Ali-Asgari; Ehsan Zahedi

    2014-01-01

    The mechanism and regioselectivity of 1,3-dipolar cycloaddition reactions of sulphur-centred 1,3-dipoles including thiocarbonyl S-imide (D1), thiocarbonyl S-oxide (D2) and thiocarbonyl S-sulphide (D3) with an electron-deficient dipolarophile, furan-2,3-dione (DPh), were studied in the light of some theoretical approaches, namely, activation energy, density functional theory (DFT) reactivity indices and Houk’s rule based on the frontier molecular orbital (FMO) theory at the B3LYP/6-311++G∗∗ level. The present analysis reveals that the cycloaddition reactions under study can be classified in the normal electron demand category. An excellent agreement was observed between the kinetic results and the electronic approaches; in fact, maximum hardness principle (MHP), Chattaraj’s polar model, Houk’s rule and the Gazquez-Mendez rule confirm the resultant regioselectivity based on the calculated activation energies.

  11. Zn-catalyzed enantio- and diastereoselective formal [4 + 2] cycloaddition involving two electron-deficient partners: asymmetric synthesis of piperidines from 1-azadienes and nitro-alkenes.

    Science.gov (United States)

    Chu, John C K; Dalton, Derek M; Rovis, Tomislav

    2015-04-08

    We report a catalytic asymmetric synthesis of piperidines through [4 + 2] cycloaddition of 1-azadienes and nitro-alkenes. The reaction uses earth abundant Zn as catalyst and is highly diastereo- and regioselective. A novel BOPA ligand (F-BOPA) confers high reactivity and enantioselectivity in the process. The presence of ortho substitution on the arenes adjacent to the bis(oxazolines) was found to be particularly impactful, due to limiting the undesired coordination of 1-azadiene to the Lewis acid and thus allowing the reaction to be carried out at lower temperature. A series of secondary kinetic isotope effect studies using a range of ligands implicates a stepwise mechanism for the transformation, involving an initial Michael-type addition of the imine to the nitro-alkene followed by a cyclization event. The stepwise mechanism obviates the electronic requirement inherent to a concerted mechanism, explaining the successful cycloaddition between two electron-deficient partners.

  12. Chemoselective Switch in the Asymmetric Organocatalysis of 5 H -Oxazol-4-ones and N -Itaconimides: Addition-Protonation or [4+2] Cycloaddition

    KAUST Repository

    Zhu, Bo

    2015-12-09

    © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. We report a synthetic strategy for a chemoselective switch and a diastereo-divergent approach for the asymmetric reaction of 5H-oxazol-4-ones and N-itaconimides catalyzed by L-tert-leucine-derived tertiary amine-urea compounds. The reaction was modulated to harness either tandem conjugate addition-protonation or [4+2] cycloaddition as major product with excellent enantio- and diastereoselectivities. Subjecting the enantio-enriched cycloaddition products to a basic silica gel reagent yields the diastereomer vis-à-vis the product directly obtained under conditions for addition-protonation, thus opening a diastereo-divergent route for creating 1,3-tertiary-hetero-quaternary stereocenters. Quantum chemical studies further provide stereochemical analysis for the [4+2] process and a plausible mechanism for this chemoselective switch is proposed.

  13. Rh(II) Catalyzed High Order Cycloadditions of 8-Azaheptafulvenes with N-Sulfonyl 1,2,3-Triazloes or α-Oxo Diazocompounds.

    Science.gov (United States)

    Chen, Wei; Bai, Ya-Li; Luo, Yong-Chun; Xu, Peng-Fei

    2017-01-20

    A novel strategy was developed for the application of Rh carbenes generated from readily accessible N-sulfonyl 1,2,3,-triazoles or diazocompouds in the high order cycloadditions, which offered an efficient route to a variety of N-containing medium-sized rings. The process provided a wide range of cyclohepta[b]pyrazine and cyclohepta[b]pyrrolone derivatives with high yields.

  14. Synthesis of Bis-pyrrolizidine-Fused Dispiro-oxindole Analogues of Curcumin via One-Pot Azomethine Ylide Cycloaddition: Experimental and Computational Approach toward Regio- and Diastereoselection.

    Science.gov (United States)

    Bharitkar, Yogesh P; Das, Mohua; Kumari, Neha; Kumari, M Padma; Hazra, Abhijit; Bhayye, Sagar S; Natarajan, Ramalingam; Shah, Siddharth; Chatterjee, Sourav; Mondal, Nirup B

    2015-09-18

    Curcumin has been transformed to racemic curcuminoids via an azomethine ylide cycloaddition reaction using isatin/acenaphthoquinone and proline as the reagents. The products were characterized by extensive 1D/2D NMR analysis and single-crystal X-ray crystallographic studies. The enantiomers of one racemic product were separated by HPLC on a Chiralcel OD-H column and were indeed confirmed by the CD spectra of the separated enantiomers.

  15. Synthesis of novel isatin-type 5'-(4-Alkyl/Aryl-1H-1,2,3-triazoles) via 1,3-dipolar cycloaddition reactions

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Bianca N. M.; Silva, Barbara V.; Pinto, Angelo C., E-mail: biancanascimento@iq.ufrj.br [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Quimica; Silva, Fernando C.; Gonzaga, Daniel T. G.; Ferreira, Vitor F. [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Instituto de Quimica

    2013-02-15

    Isatin and 1H-1,2,3-triazoles are two classes of compounds with great prominence in organic synthesis and medicinal chemistry as they are heterocycle nuclei with a high reactivity allowing to obtain several compounds with important biological properties. Herein, the synthesis of novel 5'-(4-alquil/aril-1H-1,2,3-triazole)-isatin via reaction of 1,3-dipolar cycloaddition catalyzed by acetic acid is reported. (author)

  16. 1,3-Dipolar Cycloaddition Reactions of 1-(4-Phenylphenacyl-1,10-phenanthrolinium N-Ylide with Activated Alkynes and Alkenes

    Directory of Open Access Journals (Sweden)

    A. Badoiu

    2005-02-01

    Full Text Available The 3 2 cycloaddition reaction of 1-(4-phenylphenacyl-1,10-phenanthrolinium ylide with activated alkynes gave pyrrolo[1,2- 4a][1,10]phenanthrolines 6a-d. The "one pot" synthesis of 6a,b,d from 4, activatedalkenes, Et3N and tetrakis-pyridine cobalt (II dichromate (TPCD is described. Thehelical chirality of pyrrolophenanthrolines 6b-d was put in evidence by NMRspectroscopy.

  17. A Facile Access to Fluorinated Pyrrolidines via Catalytic Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Ylides with Methyl a-Fluoroacrylate

    Institute of Scientific and Technical Information of China (English)

    严定策; 李清华; 王春江

    2012-01-01

    Asymmetric 1,3-dipolar cycloaddition of methyl a-fluoroacrylate with azomethine ylides for the construction of optically active fluorinated pyrrolidines bearing one unique fluorinated quaternary and two tertiary stereogenic cen- ters has been achieved with Cu(CH3CN)4BF4/TF-BiphamPhos complexes for the first time. This catalytic system performs well over a broad scope of substrates, providing the synthetically useful adducts in good yields and excel- lent diastereoselectivities and good to high enantioselectivities.

  18. Lewis acid-catalyzed intramolecular [3+2] cycloaddition of cyclopropane 1,1-diesters with alkynes for the synthesis of cyclopenta[c]chromene skeletons.

    Science.gov (United States)

    Xia, Xiao-Feng; Song, Xian-Rong; Liu, Xue-Yuan; Liang, Yong-Min

    2012-06-01

    An efficient method to construct cyclopenta[c]chromene skeletons by Lewis acid-catalyzed intramolecular [3+2] cycloaddition of cyclopropane 1,1-diesters with alkynes is presented. Two new fused cycles can be formed in one step in moderate to excellent yields (up to 94 %), and the products can be converted into bioactive barbituric acid derivatives (1) under simple reaction conditions. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Synthetic Studies on Bioactive Natural Polyketides: Intramolecular Nitrile Oxide-Olefin Cycloaddition Approach for Construction of a Macrolactone Skeleton of Macrosphelide B

    Directory of Open Access Journals (Sweden)

    Seung-Mann Paek

    2011-06-01

    Full Text Available Studies on the synthesis of macrosphelide B via an intramolecular nitrile oxide-olefin cycloaddition (INOC is described. In particular, an asymmetric INOC approach using phase transfer catalysts seems to be a potentially efficient and versatile procedure for the construction of the macrolactone skeleton of macrosphelide B in terms of facial selectivity. Our preliminary and unprecedented stereoselective procedure is anticipated to be usefully applied through further studies for the synthesis of the macrosphelide family.

  20. A novel protocol for the facile construction of tetrahydroquinoline fused tricyclic frameworks via an intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction.

    Science.gov (United States)

    Bakthadoss, Manickam; Vinayagam, Varathan

    2015-10-21

    An efficient method towards the synthesis of quinoline fused tricyclic compounds involving an intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction utilizing Baylis-Hillman derivatives in good yields has been described for the first time. A highly functionalized tricyclic framework was created by forming two rings and two adjacent stereocentres through the formation of two N-C bonds, one C-C bond and one O-C bond in a highly regio and diastereoselective manner.

  1. N-Heterocyclic Carbene Catalyzed [3+2] Cycloaddition of Enals with Masked Cinnamates for the Asymmetric One-Pot Synthesis of Adipic Acid Derivatives.

    Science.gov (United States)

    Chen, Xiang-Yu; Li, Sun; Sheng, He; Liu, Qiang; Jafari, Ehsan; von Essen, Carolina; Rissanen, Kari; Enders, Dieter

    2017-09-21

    A novel short entry to 3,4-disubstituted adipic acids has been developed by employing an asymmetric NHC-catalyzed [3+2] cycloaddition of enals with masked cinnammates in moderate to good yields and high stereoselectivities. The synthetic utility of the protocol was demonstrated by the basic conversion of the masked cyclopentanone intermediates to 3S,4S-disubstituted adipic acid precursors of pharmaceutically important gababutins. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Development of a tailor-made bis(oxazolidine)pyridine-metal catalyst for the [3+2] cycloaddition of azomethine imines with propiolates.

    Science.gov (United States)

    Arai, Takayoshi; Ogino, Yuta; Sato, Toru

    2013-09-14

    A series of bis(oxazolidine)pyridine ligands (the PyBodines) were newly designed and synthesized for the development of a highly efficient, tailor-made catalyst for the [3+2] cycloaddition of azomethine imines with propiolates. The PyBodine(l-Ala)-Cu(OAc)2 catalyst was selected on the basis of solid-phase catalysis/CD-HTS and exhibited high efficiency, producing the (R)-adducts with excellent enantioselectivity.

  3. Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6.

    Science.gov (United States)

    Kozikowski, Alan P; Tapadar, Subhasish; Luchini, Doris N; Kim, Ki Hwan; Billadeau, Daniel D

    2008-08-14

    A series of hydroxamate based HDAC inhibitors containing a phenylisoxazole as the CAP group has been synthesized using nitrile oxide cycloaddition chemistry. An HDAC6 selective inhibitor having a potency of approximately 2 picomolar was identified. Some of the compounds were examined for their ability to block pancreatic cancer cell growth and found to be about 10-fold more potent than SAHA. This research provides valuable, new molecular probes for use in exploring HDAC biology.

  4. Exploiting the Distal Reactivity of Indolyl Methylenemalononitriles: An Asymmetric Organocatalyzed [4+2] Cycloaddition with Enals Enables the Assembly of Elusive Dihydrocarbazoles.

    Science.gov (United States)

    Rassu, Gloria; Curti, Claudio; Zambrano, Vincenzo; Pinna, Luigi; Brindani, Nicoletta; Pelosi, Giorgio; Zanardi, Franca

    2016-08-26

    An unprecedented technique for the in situ generation of indolyl ortho-quinodimethanes from 2-methylindole-based methylenemalononitriles by amine-mediated remote C(sp(3) )-H deprotonation was developed. These intermediates were efficiently trapped by diverse enals to provide a rapid entry to 2,9-dihydro-1H-carbazole-3-carboxyaldehyde structures through a formal asymmetric [4+2] eliminative cycloaddition governed by a α,α-diphenylprolinol trimethylsilyl ether catalyst.

  5. Phosphine-catalyzed [3+2] cycloaddition reactions of azomethine imines with electron-deficient alkenes: a facile access to dinitrogen-fused heterocycles.

    Science.gov (United States)

    Li, Zhen; Yu, Hao; Liu, Honglei; Zhang, Lei; Jiang, Hui; Wang, Bo; Guo, Hongchao

    2014-02-03

    An efficient method for the phosphine-catalyzed [3+2] cycloaddition reaction of azomethine imines with diphenylsulfonyl alkenes to give dinitrogen-fused bi- or tricyclic heterocyclic compounds in high yields has been described. Moreover, two phenylsulfonyl groups installed on the heterocyclic products could be conveniently removed or transformed to other functional groups, making the reaction more useful. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. DMAP-catalyzed [3 + 2] and [4 + 2] cycloaddition reactions between [60]fullerene and unmodified Morita-Baylis-Hillman adducts in the presence of Ac2O.

    Science.gov (United States)

    Yang, Hai-Tao; Ren, Wen-Long; Miao, Chun-Bao; Dong, Chun-Ping; Yang, Yang; Xi, Hai-Tao; Meng, Qi; Jiang, Yan; Sun, Xiao-Qiang

    2013-02-01

    One-step DMAP-catalyzed [3 + 2] and [4 + 2] cycloaddition reactions between C(60) and unmodified Morita-Baylis-Hillman adducts in the presence of Ac(2)O have been developed for the easy preparation of cyclopentene- and cyclohexene-fused [60]fullerene derivatives. When the MBH adducts bear an alkyl group, two different reaction pathways could be controlled selectively depending on the conditions.

  7. Scaffold oriented synthesis. Part 3: design, synthesis and biological evaluation of novel 5-substituted indazoles as potent and selective kinase inhibitors employing [2+3] cycloadditions.

    Science.gov (United States)

    Akritopoulou-Zanze, Irini; Wakefield, Brian D; Gasiecki, Alan; Kalvin, Douglas; Johnson, Eric F; Kovar, Peter; Djuric, Stevan W

    2011-03-01

    We report the synthesis and biological evaluation of 5-substituted indazoles and amino indazoles as kinase inhibitors. The compounds were synthesized in a parallel synthesis fashion from readily available starting materials employing [2+3] cycloaddition reactions and were evaluated against a panel of kinase assays. Potent inhibitors were identified for numerous kinases such as Rock2, Gsk3β, Aurora2 and Jak2.

  8. Zn-catalyzed Enantio- and Diastereoselective Formal [4+2] Cycloaddition Involving Two Electron-Deficient Partners: Asymmetric Synthesis of Piperidines from 1-Azadienes and Nitroalkenes

    OpenAIRE

    Chu, John C. K.; Dalton, Derek M.; Rovis, Tomislav

    2015-01-01

    We report a catalytic asymmetric synthesis of piperidines through [4+2] cycloaddition of 1-azadienes and nitroalkenes. The reaction uses earth abundant Zn as catalyst, and is highly diastereo- and regio-selective. A novel BOPA ligand (F-BOPA) confers high reactivity and enantioselectivity in the process. The presence of ortho substitution on the arenes adjacent to the bis(oxazolines) was found to be particularly impactful, due to limiting the undesired coordination of 1-azadiene to the Lewis ...

  9. Rhodium-catalyzed [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes and CO: reaction design, development, application in natural product synthesis, and inspiration for developing new reactions for synthesis of eight-membered carbocycles.

    Science.gov (United States)

    Wang, Yi; Yu, Zhi-Xiang

    2015-08-18

    Practical syntheses of natural products and their analogues with eight-membered carbocyclic skeletons are important for medicinal and biological investigations. However, methods and strategies to construct the eight-membered carbocycles are limited. Therefore, developing new methods to synthesize the eight-membered carbocycles is highly desired. In this Account, we describe our development of three rhodium-catalyzed cycloadditions for the construction of the eight-membered carbocycles, which have great potential in addressing the challenges in the synthesis of medium-sized ring systems. The first reaction described in this Account is our computationally designed rhodium-catalyzed two-component [5 + 2 + 1] cycloaddition of ene-vinylcyclopropanes (ene-VCPs) and CO for the diastereoselective construction of bi- and tricyclic cyclooctenones. The design of this reaction is based on the hypothesis that the C(sp(3))-C(sp(3)) reductive elimination of the eight-membered rhodacycle intermediate generated from the rhodium-catalyzed cyclopropane cleavage and alkene insertion, giving Wender's [5 + 2] cycloadduct, is not easy. Under CO atmosphere, CO insertion may occur rapidly, converting the eight-membered rhodacycle into a nine-membered rhodacycle, which then undergoes an easy C(sp(2))-C(sp(3)) reductive elimination process and furnishes the [5 + 2 + 1] product. This hypothesis was supported by our preliminary DFT studies and also served as inspiration for the development of two [7 + 1] cycloadditions: the [7 + 1] cycloaddition of buta-1,3-dienylcyclopropanes (BDCPs) and CO for the construction of cyclooctadienones, and the benzo/[7 + 1] cycloaddition of cyclopropyl-benzocyclobutenes (CP-BCBs) and CO to synthesize the benzocyclooctenones. The efficiency of these rhodium-catalyzed cycloadditions can be revealed by the application in natural product synthesis. Two eight-membered ring-containing natural products, (±)-asterisca-3(15),6-diene and (+)-asteriscanolide, have been

  10. Inverse electron-demand 1,3-dipolar cycloaddition of nitrile oxide with common nitriles leading to 3-functionalized 1,2,4-oxadiazoles.

    Science.gov (United States)

    Nishiwaki, Nagatoshi; Kobiro, Kazuya; Hirao, Shotaro; Sawayama, Jun; Saigo, Kazuhiko; Ise, Yumiko; Okajima, Yoshikazu; Ariga, Masahiro

    2011-10-07

    A carbamoyl-substituted nitrile oxide was generated upon treatment of easily available 2-methyl-4-nitro-3-isoxazolin-5(2H)-one with THF (not dried); the reaction proceeded efficiently even in the absence of any special reagents and reaction conditions. The nitrile oxide caused 1,3-dipolar cycloaddition with common aliphatic nitriles or electron-rich aromatic nitriles to afford 3-functionalized 1,2,4-oxadiazoles, which are expected to serve as precursors for the preparation of a variety of functional materials by the chemical transformation of the carbamoyl group. While conventional preparative methods for 1,2,4-oxadiazoles involve the cycloaddition of an electron-rich nitrile oxide with an electron-deficient nitrile or a nitrile activated by a Lewis acid, our method employs the complementary combination of an electron-rich nitrile and an electron-deficient nitrile oxide- the inverse electron-demand 1,3-cycloaddition. The DFT calculations using B3LYP 6-31G* supported the abovementioned inverse reactivity, and also suggested the presence of an accelerating effect by the carbamoyl group as a result of hydrogen bond formation with a dipolarophilic nitrile.

  11. Control of light-promoted [2+2] cycloaddition reactions by a remote ancillary regulatory group that is covalently attached to rhenium rectangles.

    Science.gov (United States)

    Lu, Zong-Zhan; Lee, Chung-Chou; Velayudham, Murugesan; Lee, Li-Wei; Wu, Jing-Yun; Kuo, Ting-Shen; Lu, Kuang-Lieh

    2012-12-03

    The high-yielding self-assembly of three neutral rhenium(I) rectangles, [Re(2)(CO)(6)(L)(bpe)](2) (1 a, L=2,2'-biimidazolate (biim); 1 b, L=2,2'-bisbenzimidazolate (bbim); 1 c, L=2,2'-bis(4,5-dimethylimidazolate) (bdmim); bpe=trans-1,2-bis(4-pyridyl)ethylene), under hydrothermal conditions is described. The rectangles were structurally characterized by spectroscopic techniques and further confirmed by single-crystal X-ray diffraction. Upon irradiation with a Hg lamp at 365 nm, the bpe ligands of rectangles 1 a and 1 b underwent [2+2] photocycloaddition reactions to produce [{(Re(CO)(3))(2)L}(2)(4,4'-tpcb)(2)] (2 a, L=biim; 2 b, L=bbim; 4,4'-tpcb=1,2,3,4-tetrakis(4-pyridyl)cyclobutane) through a single-crystal-to-single-crystal (SCSC) transformation. However, rectangle 1 c, which contained methyl groups on the 2,2'-biimidazolate ligand, failed to undergo cycloaddition, even after prolonged irradiation. This result indicates that the light-induced cycloaddition reaction can be preferentially controlled by the remote regulatory substituents, which are attached onto the same backbone of the rectangle complex. This transformation is the first reported utilization of a remote ancillary regulatory ligand that is covalently attached onto a coordination compound to control the [2+2] cycloaddition reaction. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Inverse Electron Demand Diels–Alder Reactions of 1,2,3-Triazines: Pronounced Substituent Effects on Reactivity and Cycloaddition Scope

    Science.gov (United States)

    Anderson, Erin D.; Boger, Dale L.

    2011-01-01

    A systematic study of the inverse electron demand Diels–Alder reactions of 1,2,3-triazines is disclosed, including an examination of the impact of a C5 substituent. Such substituents were found to exhibit a remarkable impact on the cycloaddition reactivity of the 1,2,3-triazine without altering, and perhaps even enhancing, the intrinsic cycloaddition regioselectivity. The study revealed that not only may the reactivity be predictably modulated by a C5 substituent (R = CO2Me > Ph > H), but that the impact is of a magnitude to convert 1,2,3-triazine (1) and its modest cycloaddition scope into a heterocyclic azadiene system with a reaction scope that portends extensive synthetic utility, expanding the range of participating dienophiles. Significantly, the studies define a now powerful additional heterocyclic azadiene, complementary to the isomeric 1,2,4-triazines and 1,3,5-triazines, capable of dependable participation in inverse electron demand Diels–Alder reactions, extending the number of complementary heterocyclic ring systems accessible with implementation of the methodology. PMID:21736324

  13. Novel carbamoyl type quinine and quinidine based chiral anion exchangers implementing alkyne-azide cycloaddition immobilization chemistry.

    Science.gov (United States)

    Hettegger, Hubert; Kohout, Michal; Mimini, Vebi; Lindner, Wolfgang

    2014-04-11

    The synthesis and chromatographic evaluation of a series of new Cinchona derived chiral weak anion exchangers is presented. Huisgen Cu(I) mediated alkyne-azide cycloaddition, so-called click chemistry, was used as an immobilization strategy. In this way it was possible to immobilize about 90% of offered selector via 1,2,3-triazole linker, which displays a more efficient way of binding the selector to modified silica compared to common radical mediated thiol-ene addition. Problems associated with potential radical scavenging properties of chiral selectors thereby could be circumvented. The evaluation of the synthesized chiral stationary phases regarding chromatographic behavior was carried out using polar organic mode mobile phase composition and a set of representative chiral organic acids. Different loading densities revealed an optimum selector density of about 310μmol/g chiral stationary phase with respect to resolution and selectivity. A decrease of performance was observed for higher loading, indicating mutual spatial influence of selector units leading to sterical hindrance. In addition, we observed that the effect of free azide groups on retention is negligible and the overall chromatographic behavior is comparable to other Cinchona derived chiral stationary phases.

  14. Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes.

    Science.gov (United States)

    Mlostoń, Grzegorz; Pipiak, Paulina; Heimgartner, Heinz

    2016-01-01

    Reactions of dihetaryl and aryl/hetaryl thioketones with 2-diazopropane, diazoethane, and (trimethylsilyl)diazomethane were studied at variable temperature. The experiments showed that reactions with 2-diazopropane carried out at -75 °C occur mainly via the initially formed, relatively stable 1,3,4-thiadiazolines as products of the [3 + 2]-cycloaddition of the diazo dipole onto the C=S bond. The latter decompose only at higher temperature (ca. -40 °C) to generate thiocarbonyl S-isopropanide. In the absence of the starting thioketone, the corresponding thiiranes and/or ethene derivatives, formed from them via spontaneous desulfurization, are the main products. In contrast, reactions with diazoethane occurred predominantly via initially formed diradicals, which in cascade processes gave sterically crowded 4,4,5,5-tetrahetaryl-1,3-dithiolanes as major products. Finally, the reaction of dihetaryl thioketones with (trimethylsilyl)diazomethane occur smoothly at -75 °C leading to the corresponding 4,4,5,5-tetrahetaryl-1,3-dithiolanes as the exclusive [3 + 2]-cycloadducts formed via a cascade of postulated diradicals. The presence of S or Se atoms in the hetaryl rings is of importance for stabilizing diradical intermediates. Remarkably, in no single case, the 'head-to-head dimerization' of aryl/hetaryl and dihetaryl substituted thiocarbonyl ylides was observed.

  15. Lateral extension of π conjugation along the bay regions of bisanthene through a diels-alder cycloaddition reaction

    KAUST Repository

    Li, Jinling

    2011-11-14

    Diels-Alder cycloaddition reactions at the bay regions of bisanthene (1) with dienophiles such as 1,4-naphthoquinone have been investigated. The products were submitted to nucleophilic addition followed by reductive aromatization reactions to afford the laterally extended bisanthene derivatives 2 and 3. Attempted synthesis of a larger expanded bisanthene 4 revealed an unexpected hydrogenation reaction at the last reductive aromatization step. Unusual Michael addition was observed on quinone 14, which was obtained by Diels-Alder reaction between 1 and 1,4-anthraquinone. Compounds 1-3 exhibited near-infrared (NIR) absorption and emission with high-to-moderate fluorescent quantum yields. Their structures and absorption spectra were studied by density function theory and non-planar twisted structures were calculated for 2 and 3. All compounds showed amphoteric redox behavior with multiple oxidation/reduction waves. Oxidative titration with SbCl 5 gave stable radical cations, and the process was followed by UV/Vis/NIR spectroscopic measurements. Their photostability was measured and correlated to their different geometries and electronic structures. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. One-pot sequential alkynylation and cycloaddition: regioselective construction and biological evaluation of novel benzoxazole-triazole derivatives.

    Science.gov (United States)

    Srivastava, Ananya; Aggarwal, Leena; Jain, Nidhi

    2015-01-12

    Individually, benzoxazole and triazole moieties are of significant biological interest owing to their importance in drugs and pharmaceuticals. To assess their combined biological impact when woven into one molecule, we designed a novel, regioselective, multicomponent, one-pot (MCOP) approach for the construction of benzoxazole-linked triazoles. The synthesis has been achieved in two sequential steps involving copper-catalyzed alkynylation of benzoxazole followed by a 1,3-dipolar cycloaddition reaction. By combination of these two bioactive units into one core, a series of new benzoxazole-triazole scaffolds has been synthesized and subjected to in vitro antibacterial and anticancer evaluation. Tests against clinical isolates of Staphylococcus aureus and Escherichia coli showed potent Gram-negative activity for compounds 4{1,1,1}, 4{1,1,4}, and 4{1,2,1}. The cytotoxicity of the synthesized library was determined against three cancer cell lines: HeLa, SKBr3, and Hep G2. Compound 4{2,2,2} showed significant cytotoxicity against all the cell lines. These preliminary bioassay evaluations strongly suggest the promise and scope of these novel molecules as therapeutic agents in medical science.

  17. Organic functionalization of the Si (100) and Ge (100) surfaces by cycloadditions of carbenes and nitrenes: a theoretical prediction.

    Science.gov (United States)

    Xu, Yi-Jun; Zhang, Yong-Fan; Li, Jun-Qian

    2006-02-23

    By means of density functional theory (B3LYP/6-31G*) coupled with effective cluster models, we predict that the well-known cycloaddition reactions of carbenes and nitrenes to alkenes in organic chemistry can be employed as a new type of surface reaction to organically functionalize the Si (100) and Ge (100) surfaces at low temperature. The well-established abundance of carbenes and nitrenes addition chemistry in organic chemistry provides versatile flexibility of functionalizing the surfaces of Si (100) and Ge (100), which can potentially impart new organic functionalities to the semiconductors surface for novel applications in a diversity of fields. Our predictions strongly advance the concept of using organic reactions to modify the solid surface in a controlled manner and quite intriguing chemistry can lie in the material featuring the analogous bonding motif. In further perspective, implications for other theoretical work, regarding disilenes, digermenes, silenes, and germenes that all feature the bonding motif similar to alkenes, are also discussed.

  18. Silver-catalysed azide–alkyne cycloaddition (AgAAC): assessing the mechanism by density functional theory calculations

    Science.gov (United States)

    Chandrasekhar, K.; Killi, Sunil Kumar; Pramanik, Sumit Kumar; Uttam, Pal; Sen, Sudeshna; Maiti, Nakul Chandra

    2016-01-01

    ‘Click reactions’ are the copper catalysed dipolar cycloaddition reaction of azides and alkynes to incorporate nitrogens into a cyclic hydrocarbon scaffold forming a triazole ring. Owing to its efficiency and versatility, this reaction and the products, triazole-containing heterocycles, have immense importance in medicinal chemistry. Copper is the only known catalyst to carry out this reaction, the mechanism of which remains unclear. We report here that the ‘click reactions’ can also be catalysed by silver halides in non-aqueous medium. It constitutes an alternative to the well-known CuAAC click reaction. The yield of the reaction varies on the type of counter ion present in the silver salt. This reaction exhibits significant features, such as high regioselectivity, mild reaction conditions, easy availability of substrates and reasonably good yields. In this communication, the findings of a new catalyst along with the effect of solvent and counter ions will help to decipher the still obscure mechanism of this important reaction. PMID:27703683

  19. Properties of Poly(ethylene glycol) Hydrogels Cross-Linked via Strain-Promoted Alkyne-Azide Cycloaddition (SPAAC).

    Science.gov (United States)

    Hodgson, Sabrina M; Bakaic, Emilia; Stewart, S Alison; Hoare, Todd; Adronov, Alex

    2016-03-14

    A series of poly(ethylene glycol) (PEG) hydrogels was synthesized using strain-promoted alkyne-azide cycloaddition (SPAAC) between PEG chains terminated with either aza-dibenzocyclooctynes or azide functionalities. The gelation process was found to occur rapidly upon mixing the two components in aqueous solution without the need for external stimuli or catalysts, making the system a candidate for use as an injectable hydrogel. The mechanical and rheological properties of these hydrogels were found to be tunable by varying the polymer molecular weight and the number of cross-linking groups per chain. The gelation times of these hydrogels ranged from 10 to 60 s at room temperature. The mass-based swelling ratios varied from 45 to 76 at maximum swelling (relative to the dry state), while the weight percent of polymer in these hydrogels ranged from 1.31 to 2.05%, demonstrating the variations in amount of polymer required to maintain the structural integrity of the gel. Each hydrogel degraded at a different rate in PBS at pH = 7.4, with degradation times ranging from 1 to 35 days. By changing the composition of the two starting components, it was found that the Young's modulus of each hydrogel could be varied from 1 to 18 kPa. Hydrogel incubation with bovine serum albumin showed minimal protein adsorption. Finally, a cell cytotoxicity study of the precursor polymers with 3T3 fibroblasts demonstrated that the azide- and strained alkyne-functionalized PEGs are noncytotoxic.

  20. N-(furfural) chitosan hydrogels based on Diels-Alder cycloadditions and application as microspheres for controlled drug release.

    Science.gov (United States)

    Montiel-Herrera, Marcelino; Gandini, Alessandro; Goycoolea, Francisco M; Jacobsen, Neil E; Lizardi-Mendoza, Jaime; Recillas-Mota, Maricarmen; Argüelles-Monal, Waldo M

    2015-09-01

    In this study, chitosan was chemically modified by reductive amination in a two-step process. The synthesis of N-(furfural) chitosan (FC) was confirmed by FT-IR and (1)H NMR analysis, and the degrees of substitution were estimated as 8.3 and 23.8%. The cross-linkable system of bismaleimide (BM) and FC shows that FC shared properties of furan-maleimide chemistry. This system produced non-reversible hydrogel networks by Diels-Alder cycloadditions at 85 °C. The system composed of BM and FC (23.8% substitution) generated stronger hydrogel networks than those of FC with an 8.3% degree of substitution. Moreover, the FC-BM system was able to produce hydrogel microspheres. Environmental scanning electron microscopy revealed the surface of the microspheres to be non-porous with small protuberances. In water, the microspheres swelled, increasing their volume by 30%. Finally, microspheres loaded with methylene blue were able to release the dye gradually, obeying second-order kinetics for times less than 600 min. This behavior suggests that diffusion is governed by the relaxation of polymer chains in the swelled state, thus facilitating drug release outside the microspheres.

  1. Supramolecular chemistry of pillar[n]arenes functionalised by a copper(i)-catalysed alkyne-azide cycloaddition "click" reaction.

    Science.gov (United States)

    Kakuta, T; Yamagishi, T; Ogoshi, T

    2017-05-09

    Since we discovered pillar[n]arenes in 2008, many chemists have developed a strong interest in pillar[n]arene chemistry because of the many advantages associated with these materials, including their facile and high yielding synthesis, versatile functionality, planar chirality and unique host-guest properties. In this feature article, we discuss recent advances in the field of supramolecular chemistry based on the use of pillar[n]arenes as substrates for copper(i)-catalysed alkyne-azide cycloaddition (CuAAC) "click" chemistry. The CuAAC reaction provides facile access to 1,4-disubstituted triazoles by a reaction between alkyne and azido substrates in the presence of a Cu(i) catalyst. Pillar[n]arenes bearing alkyne or azido groups can therefore be used as substrates for this reaction. Herein, we discuss not only the synthesis of pillar[n]arenes bearing alkyne or azido groups but also the application of these functionalised systems to the CuAAC reaction to construct supramolecular assemblies. We also discuss the rational molecular design and synthesis of guest compounds using the CuAAC reaction because linear alkanes sandwiched between 1,2,3-triazole moieties are good guests for cyclic pentamer pillar[5]arenes.

  2. Ab initio Study of Mechanism of Cycloaddition Reaction be- tween Germylene Silylene (H2Ge=Si:) and Acetone%Ab initio Study of Mechanism of Cycloaddition Reaction be- tween Germylene Silylene (H2Ge=Si:) and Acetone

    Institute of Scientific and Technical Information of China (English)

    Lu, Xiuhui; Han, Junfeng; Li, Yongqing; Wang, Zhina

    2011-01-01

    The mechanism of the cycloaddition reaction between singlet germylene silylene (H2Ge =Si:) and acetone has been investigated with CCSD(T)/6-31G*//MP2/6-31 G* method. From the potential energy profile, we could predict that the reaction has two competitive dominant reaction channels. The present rule of this reaction is that the [2 +2] cycloaddition reaction of the two π-bonds in germylene silylene and acetone generates a four-membered ring silylene with Ge. Because of the unsaturated property of Si atom in the four-membered ring silylene with Ge, it could further react with acetone, resulting in the generation of a bis-heterocyclic compound with Si and Ge. Simul- taneously, the ring strain of the four-membered ring silylene with Ge makes it isomerize to a twisted four-membered ring product.

  3. Theoretical Evaluation of the Global and Local Electrophilicity Patterns to Characterize Hetero Diels-Alder Cycloaddition in the Synthesis of Isoxazolo[4,5-e](1,2,3,4-tetrazine)

    Institute of Scientific and Technical Information of China (English)

    SHARMA,Pratibha; KUMAR,Ashok; SINGH,Jitendra; SAHU,Vinita

    2009-01-01

    A series of substituted dienophiles 1-10 and three 1,2-diazadienes namely D-1, D-2, D-3 were chosen to understand the reactivity and selectivity of Diels-Alder cycloaddition. The global and local electrophilicity patterns have been evaluated on a series of cycloaddition reactions to assess the reaction pathways (NDAC/IEDDAC) using the absolute scale of electrophilicity proposed by Parr et aL Regional electrophilicity at the active sites of the re-agents involved in Diels-Alder processes has been described on a quantitative basis using local or regional electro-philicity index I.e. Fukui function. Good qualitative/quantitative comparison was found between molecular energy gaps and global electronic parameters, which has been employed to assess the cycloaddition pathways successfully.

  4. A supported copper hydroxide on titanium oxide as an efficient reusable heterogeneous catalyst for 1,3-dipolar cycloaddition of organic azides to terminal alkynes.

    Science.gov (United States)

    Yamaguchi, Kazuya; Oishi, Takamichi; Katayama, Tatsuyori; Mizuno, Noritaka

    2009-10-12

    An easily prepared supported copper hydroxide on titanium oxide (Cu(OH)(x)/TiO(2)) showed high catalytic performance for the 1,3-dipolar cycloaddition of organic azides to terminal alkynes in non-polar solvents under anaerobic conditions. The reactions of various combinations of organic azides (four examples, including aromatic and aliphatic ones) and terminal alkynes (eleven examples, including aromatic, aliphatic, and double bond-containing ones) exclusively proceeded to give the corresponding 1,4-disubstituted-1,2,3-triazole derivatives in a completely regioselective manner. For the transformation of benzyl azide and ethynylbenzene with 0.12 mol % of Cu(OH)(x)/TiO(2), the turnover frequency was 505 h(-1) and the turnover number reached up to 800. These values were the highest among those with previously reported heterogeneous catalysts including Cu(OH)(x)/Al(2)O(3). The observed catalysis was truly heterogeneous and the retrieved catalyst after the reaction could be reused at least three times with retention of its high catalytic performance. It was confirmed by the UV/Vis spectrum of Cu(OH)(x)/TiO(2) and the amount of diyne formed that the Cu(II) species in Cu(OH)(x)/TiO(2) were reduced to Cu(I) species by the alkyne-alkyne homocoupling at the initial stage of the reaction (during the pretreatment of Cu(OH)(x)/TiO(2) with an alkyne). The catalytic reaction rate for the 1,3-dipolar cycloaddition linearly increased with an increase in the amount of in situ generated Cu(I) species. Therefore, the in situ generated Cu(I) species would be the catalytically active species for the present 1,3-dipolar cycloaddition.

  5. Synthesis of unsymmetrical substituted 1,4-dihydropyridines through thermal and microwave assisted [4+2] cycloadditions of 1-azadienes and allenic esters.

    Science.gov (United States)

    Singh, Lakhwinder; Ishar, M P Singh; Elango, Munusamy; Subramanian, Venkatesan; Gupta, Vivek; Kanwal, Priyanka

    2008-03-21

    Thermal and microwave assisted [4+2] cycloadditions of 1,4-diaryl-1-aza-1,3-butadienes with allenic esters lead to cycloadducts, which after a 1,3-H shift afford variedly substituted unsymmetrical 2-alkyl-1,4-diaryl-3-ethoxycarbonyl-1,4-dihydropyridines in high yields. Reactions carried out under microwave irradiation are cleaner and give higher yields with much shortened reaction times. Density functional theory (DFT) at the B3LYP/6-31G* level has been used to calculate geometric features of the reactants, barrier for s-trans to s-cis and reverse isomerization of azadienes (5a-d, 10a-e), dihedral angles between N(1), C(2), C(3), and C(4) atoms of azadienes along with various indices such as chemical hardness (eta), chemical potential (micro), global electrophilicity (omega), and the difference in global electrophilicity (Deltaomega) between the reacting pairs and Fukui functions (f (+) and f(-)). The results revealed that s-trans is the predominant conformation of azadienes at ambient temperature and the barrier for conversion of the s-trans rotamer of 1-azadienes to s-cis may be the major factor influencing the chemoselectivity, i.e., [4+2] verses [2+2] cycloaddition. The regiochemistry of the observed cycloadditions is collated with the obtained local electrophilicity indices (Fukui functions). Transition states for the formation of both [4+2] and [2+2] cycloadducts as located at the PM3 level indicate that the transition state for the formation of [4+2] cycloadducts has lower energy, again supporting the earlier conclusion that preferred formation of [4+2] cycloaaducts at higher temperature may be a consequence of barrier for s-trans to s-cis transformation of 1-azadienes.

  6. Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

    Science.gov (United States)

    Filichev, Vyacheslav V; Boutorine, Alexandre S

    2016-01-01

    Summary Efficient protocols based on Cu(I)-catalyzed azide–alkyne cycloaddition were developed for the synthesis of conjugates of pyrrole–imidazole polyamide minor groove binders (MGB) with fluorophores and with triplex-forming oligonucleotides (TFOs). Diverse bifunctional linkers were synthesized and used for the insertion of terminal azides or alkynes into TFOs and MGBs. The formation of stable triple helices by TFO-MGB conjugates was evaluated by gel-shift experiments. The presence of MGB in these conjugates did not affect the binding parameters (affinity and triplex stability) of the parent TFOs. PMID:27559384

  7. KF/Al2O3 as a Recyclable Basic Catalyst for 1,3-Dipolar Cycloaddition Reaction: Synthesis of Indolizine-1-Carbonitrile Derivatives

    Directory of Open Access Journals (Sweden)

    Abaszadeh Mehdi

    2017-07-01

    Full Text Available KF/Al2O3 as a green and efficient catalyst has been used for synthesis of indolizine-1-carbonitrile derivatives. It can be proceeded by using 1,3-dipolar cycloaddition reaction of 1-alkyl-2-chloropyridinium bromides, malononitrile and benzaldehyde in ethanol, at reflux. The great advantage of this catalyst is the ease of handling. KF/Al2O3 can be used and removed by filtration, avoiding cumbersome aqueous workups and decreasing solvent waste handling issues. High conversions, short reaction times and a cleaner reaction profiles are some of the outstanding advantages of this method.

  8. Mono and dinuclear arene ruthenium(II) triazoles by 1,3-dipolar cycloadditions to a coordinated azide in ruthenium(II) compounds

    Digital Repository Service at National Institute of Oceanography (India)

    Singh; Svitlyk, V.; Mozharivskyj, Y.

    : Dalton Trans., vol.40(5); 2011; 1020-1023 Mono and dinuclear arene ruthenium (II) triazoles by 1,3-dipolar cycloadditions to a coordinated azide in ruthenium(II) compounds Keisham Sarjit Singh a* , Volodymyr Svitlyk b , Yurij Mozharivskyj b a.... Kauffmann, Angew. Chem., Int. Ed. Engl., 1974, 13, 627-639. 7 Z.- X. Wang, H.- L. Qin, Chem. Commun., 2003, 2450-2451. 10 8 Z. Dori, R. F. Ziolo, Chem. Rev., 1973, 73, 247-254. 9 (a) K. S. Singh, K. A. Kreisel, G. P. Yap, M. R. Kollipara, J. Organomet...

  9. Ultrasound-promoted organocatalytic enamine–azide [3 + 2] cycloaddition reactions for the synthesis of ((arylselanylphenyl-1H-1,2,3-triazol-4-ylketones

    Directory of Open Access Journals (Sweden)

    Gabriel P. Costa

    2017-04-01

    Full Text Available The use of sonochemistry is described in the organocatalytic enamine–azide [3 + 2] cycloaddition between 1,3-diketones and aryl azidophenyl selenides. These sonochemically promoted reactions were found to be amenable to a range of 1,3-diketones or aryl azidophenyl selenides, providing an efficient access to new ((arylselanylphenyl-1H-1,2,3-triazol-4-ylketones in good to excellent yields and short reaction times. In addition, this protocol was extended to β-keto esters, β-keto amides and α-cyano ketones. Selanyltriazoyl carboxylates, carboxamides and carbonitriles were synthesized in high yields at short times of reaction under very mild reaction conditions.

  10. Gold-Catalyzed β-Regioselective Formal [3 + 2] Cycloaddition of Ynamides with Pyrido[1,2-b]indazoles: Reaction Development and Mechanistic Insights.

    Science.gov (United States)

    Yu, Yinghua; Chen, Gui; Zhu, Lei; Liao, Yun; Wu, Yufeng; Huang, Xueliang

    2016-09-16

    Here, we report an unprecedented gold(I)-induced β-site regioselective formal [3 + 2] cycloaddition of ynamides with pyrido[1,2-b]indazoles, giving 3-amido-7-(pyrid-2'-yl)indoles in good to excellent yields. A complex of gold(I) catalyst with ynamide was isolated and characterized by X-ray diffraction analysis for the first time. Mechanistic investigations suggest the reaction pathway involves a gold-stabilized carbocation intermediate, which in turn participated in sequential C-H bond functionalization of the ortho-position of the phenyl ring.

  11. A conceptual DFT approach towards analysing feasibility of the intramolecular cycloaddition Diels-Alder reaction of triene amide in Lewis acid catalyst

    Indian Academy of Sciences (India)

    ABDELILAH BENALLOU; HABIB EL ALAOUI EL ABDALLAOUI; HOCINE GARMES

    2016-09-01

    The effect of Lewis acid catalysts, TiCl₄ and Et₂AlCl on the intramolecular cycloaddition Diels- Alder (IMDA) reaction of triene-amide have been studied theoretically using the DFT (Density Functional Theory) at the 6-31G(d,p) level of theory. The results obtained using the polar model of Domingo, electrophilicity, nucleophilicity indices and thermochemistry computations, demonstrate that these catalysts are coordinated with more nucleophilic atoms of diene fragment (nitrogen and oxygen of amide group). These catalysts affect negatively the feasibility of the reaction as well as the physico-chemical parameters of the IMDA reaction of triene-amide.

  12. Bifunctional Imidazolium-Based Ionic Liquid Decorated UiO-67 Type MOF for Selective CO2 Adsorption and Catalytic Property for CO2 Cycloaddition with Epoxides.

    Science.gov (United States)

    Ding, Luo-Gang; Yao, Bing-Jian; Jiang, Wei-Ling; Li, Jiang-Tao; Fu, Qi-Juan; Li, Yan-An; Liu, Zhen-Hua; Ma, Jian-Ping; Dong, Yu-Bin

    2017-02-20

    A bifunctional robust and highly porous imidazolium-based ionic liquid decorated UiO-67 type MOF (UiO-67-IL, 1) was successfully constructed via solvothermal assembly of the imidazolium-based ligand and Zr(IV) ions. It exhibits a highly selective adsorption for CO2 over CH4 and N2. Furthermore, 1 herein can be used as a highly active heterogeneous catalyst for CO2 cycloaddition with epoxides under atmospheric pressure with or without cocatalyst TBAB (n-Bu4NBr).

  13. Novel Synthesis of 1,2,3-Triazoles via 1,3-Dipolar Cycloadditions of Alkynes to Azides in Ionic Liquid

    Institute of Scientific and Technical Information of China (English)

    ZHONG,Ping(钟平); GUO,Sheng-Rong(郭圣荣)

    2004-01-01

    2-Azido-3,5-dichloropyridine and 2-azido-5-chloro-3-fluoropyridine were given by reaction of sodium azide with 2,3,5-trichloropyridine, 3,5-dichloro-2-fluoropyridine or 5-chloro-2,3-difiuoropyridine in ionic liquids.1,3-Dipolar cycloaddition of 2-azido-3,5-dichloropyridine or 2-azido-5-chloro-3-fluoropyridine to alkynes in ionic liquids afforded the corresponding 1,4,5-trisubstituted [1,2,3]-triazoles in good yields and regioselectivities.

  14. Azide-enolate 1,3-dipolar cycloaddition in the synthesis of novel triazole-based miconazole analogues as promising antifungal agents.

    Science.gov (United States)

    González-Calderón, Davir; Mejía-Dionicio, María G; Morales-Reza, Marco A; Ramírez-Villalva, Alejandra; Morales-Rodríguez, Macario; Jauregui-Rodríguez, Bertha; Díaz-Torres, Eduardo; González-Romero, Carlos; Fuentes-Benítes, Aydeé

    2016-04-13

    Seven miconazole analogs involving 1,4,5-tri and 1,5-disubstituted triazole moieties were synthesized by azide-enolate 1,3-dipolar cycloaddition. The antifungal activity of these compounds was evaluated in vitro against four filamentous fungi, including Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae, and Mucor hiemalis as well as three species of Candida spp. as yeast specimens. These pre-clinical studies suggest that compounds 4b, 4d and 7b can be considered as drug candidates for future complementary biological studies due to their good/excellent antifungal activities.

  15. On the regioselectivity of the mononuclear copper-catalyzed cycloaddition of azide and alkynes (CuAAC). A quantum chemical topological study.

    Science.gov (United States)

    Calvo-Losada, Saturnino; Pino, María Soledad; Quirante, José Joaquín

    2014-04-01

    New density functional theory (DFT) calculations show that the nature of the mechanism for the classical copper-catalyzed cycloaddition of azide to terminal alkynes--widely known as the CuAAC reaction--also depends on the ligands attached to Cu(I). Further, the topological evolution of the charge density, ρ (r), the laplacian of ρ (r), ∇²ρ(r), and its gradient field along the reaction coordinate shed light on the regioselectivity of the process. The performance of most suitable functionals for DFT calculations in this kind of system was tested.

  16. 1,3-Dipolar cycloaddition of a cyclic nitrone derived from 2-deoxy-D-ribose to α,β-unsaturated lactones: An entry to carbapenem antibiotics.

    Science.gov (United States)

    Pieczykolan, Michał; Staszewska-Krajewska, Olga; Furman, Bartłomiej; Chmielewski, Marek

    2016-10-04

    1,3-Dipolar cycloadditions of 2-deoxy-D-ribose-derived L-threo five-membered cyclic nitrone to α,β-unsaturated γ- and δ-lactones were investigated. Cycloadducts obtained from δ-lactones, after NO bond cleavage, opening of the lactone ring, and protection of hydroxyl groups were subjected to β-lactam ring formation by using Mukaiyama's salt. Cycloadducts from γ-lactones subjected to the same reaction sequence undergo β-elimination of a water molecule to provide pyrrolidine-substituted unsaturated γ-lactones. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Periselectivity switch of acylketenes in cycloadditions with 1-azadienes: microwave-assisted diastereoselective domino three-component synthesis of α-spiro-δ-lactams.

    Science.gov (United States)

    Presset, Marc; Coquerel, Yoann; Rodriguez, Jean

    2010-09-17

    The microwave-assisted Wolff rearrangement of cyclic 2-diazo-1,3-diketones in the presence of primary amines and α,β-unsaturated aldehydes provides a straightforward three-component stereoselective access to a variety of α-spiro-δ-lactams following an imination/Wolff rearrangement/[2 + 4] cycloaddition domino sequence. With aniline derivatives, a complementary aza-Wittig/Wolff rearrangement/[2 + 4] sequence was developed. These reactions feature an unprecedented reactivity of acylketenes as dienophiles in 6π electrocyclic processes.

  18. Carbonic anhydrase inhibitors developed through 'click tailing'.

    Science.gov (United States)

    Lopez, Marie; Salmon, Adam J; Supuran, Claudiu T; Poulsen, Sally-Ann

    2010-01-01

    In recent years there has been renewed activity in the literature concerning the 1,3-dipolar cycloaddition reaction (1,3-DCR) of organic azides (R-N₃) with alkynes (R'-C≡CH) to form 1,2,3-triazoles, i.e. the Huisgen synthesis. The use of catalytic Cu(I) leads to a dramatic rate enhancement (up to 10(7)-fold) and exclusive synthesis of the 1,4-disubstituted 1,2,3-triazole product. The reaction, now referred to as the copper-catalyzed azide-alkyne cycloaddition (CuAAC), meets the stringent criteria of a click-reaction in that it is modular, wide in scope, high yielding, has no byproducts, operates in water at ambient temperature, product purification is simple and the starting materials are readily available. The 1,3-DCR reaction has rapidly become the premier click chemistry reaction with applications spanning modern chemistry disciplines, including medicinal chemistry. Recently the 'tail' approach initiative for the development of carbonic anhydrase inhibitors (CAIs) has been combined with the synthetic versatility of click chemistry. This has proven a powerful combination leading to the synthesis of CAIs with useful biopharmaceutical properties and activities. This review will discuss complementary and contrasting applications that have utilized 'click tailing' for the development of CAIs. Applications encompass i) medicinal chemistry and drug discovery; ii) radiopharmaceutical development of positron emission topography (PET) chemical probes; and iii) in situ click chemistry.

  19. Alkyne-azide click reaction catalyzed by metallic copper under ultrasound.

    Science.gov (United States)

    Cintas, Pedro; Barge, Alessandro; Tagliapietra, Silvia; Boffa, Luisa; Cravotto, Giancarlo

    2010-03-01

    This protocol is for the ultrasound (US)-assisted 1,3-dipolar cycloaddition reaction of azides and alkynes using metallic copper (Cu) as the catalyst. The azido group is a willing participant in this kind of organic reaction and its coupling with alkynes is substantially improved in the presence of Cu(I). This protocol does not require additional ligands and proceeds with excellent yields. The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) is generally recognized as the most striking example of 'click chemistry'. Reactions involving metals represent the favorite domain of sonochemistry because US favors mechanical depassivation and enhances both mass transfer and electron transfer from the metal to the organic acceptor. The reaction rate increases still further when simultaneous US and microwave irradiation are applied. The US-assisted click synthesis has been applied for the preparation of a wide range of 1,4-disubstituted 1,2,3-triazole derivatives starting both from small molecules and oligomers such as cyclodextrins (CDs). Using this efficient and greener protocol, all the adducts can be synthesized in 2-4 h (including work-up and excluding characterization). Click chemistry has been shown to be able to directly link chemistry to biology, thus becoming a true interdisciplinary reaction with extremely wide applicability.

  20. The Diels-Alder Cycloaddition Reaction of Substituted Hemifullerenes with 1,3-Butadiene: Effect of Electron-Donating and Electron-Withdrawing Substituents

    Directory of Open Access Journals (Sweden)

    Martha Mojica

    2016-02-01

    Full Text Available The Diels-Alder (DA reaction provides an attractive route to increase the number of six member rings in substituted Polycyclic Aromatic Hydrocarbons (PAHs. The density functional theory (DFT B3LYP method has been used in this work to inquire if the substitution of H over the edge of triindenetriphenylene (pristine hemifullerene 1 and pentacyclopentacorannulene (pristine hemifullerene 2, could improve the DA cycloaddition reaction with 1,3-butadiene. The substituents tested include electron-donating (NH2, OMe, OH, Me, i-Pr and electron-withdrawing groups (F, COOH, CF3, CHO, CN, NO2. The electronic, kinetic and thermodynamic parameters of the DA reactions of the substituted hemifullerenes with 1,3-butadiene have been analyzed. The most promising results were obtained for the NO2 substituent; the activation energy barriers for reactions using this substituent were lower than the barriers for the pristine hemifullerenes. This leads us to expect that the cycloadditions to a starting fullerene fragment will be possible.

  1. Synthesis of Isoxazole and 1,2,3-Triazole Isoindole Derivatives via Silver- and Copper-Catalyzed 1,3-Dipolar Cycloaddition Reaction.

    Science.gov (United States)

    Rammah, Mohamed Mehdi; Gati, Wafa; Mtiraoui, Hasan; Rammah, Mohamed El Baker; Ciamala, Kabula; Knorr, Michael; Rousselin, Yoann; Kubicki, Marek M

    2016-03-04

    The CuI- or Ag₂CO₃-catalyzed [3+2] cycloaddition of propargyl-substituted dihydroisoindolin-1-one (3) with arylnitrile oxides 1a-d (Ar = Ph, p-MeC₆H₄, p-MeOC₆H₄, p-ClC₆H₄) produces in good yields novel 3,5-disubstituted isoxazoles 4 of the ethyl-2-benzyl-3-oxo-1-((3-arylisoxazol-5yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylate type. With aryl azides 2a-d (Ar = Ph, p-MeC₆H₄, p-OMeC₆H₄, p-ClC₆H₄), a series of 1,4-disubstituted 1,2,3-triazoles 6 (ethyl-2-benzyl-3-oxo-1-((1-aryl-1H-1,2,3-triazol-4-yl)methyl)-2,3-dihydro-1H-isoindole-1-carboxylates) was obtained. The reactions proceed in a regioselective manner affording exclusively racemic adducts 4 and 6. Compared to the uncatalyzed cycloaddition, the yields are significantly improved in the presence of CuI as catalyst, without alteration of the selectivity. The regio- and stereochemistry of the cycloadducts has been corroborated by an X-ray diffraction study of 4a, and in the case of 6a by XH-correlation and HMBC spectra.

  2. Theoretical Study of the Mechanism of Cycloaddition Reaction between Silylene Silylene (H2Si=Si:) and Acetone

    Institute of Scientific and Technical Information of China (English)

    汪智娜; 时乐义; 李永庆; 卢秀慧

    2012-01-01

    The mechanism of the cycloaddition reaction between singlet silylene silylene (H2Si = Si:) and acetone has been investigated with the CCSD (T)//MP2/6-31 G* method, According to the potential energy profile, it can be predicted that the reaction has two competitive dominant reaction channels. The present rule of this reaction is that the [2 + 2] cycloaddition reaction of the two ~-bonds in silylene silylene (H2Si=Si:) and acetone leads to the formation of a four-membered ring silylene (E3). Because of the unsaturated property of Si: atom in E3, it further reacts with ace- tone to form a silicic bis-heterocyclic compound (P7). Simultaneously, the ring strain of the four-membered ring silylene (E3) makes it isomerize to a twisted four-membered ring product (P4).

  3. A theoretical investigation on the regioselectivity of the intramolecular hetero Diels-Alder and 1,3-dipolar cycloaddition of 2-vinyloxybenzaldehyde derivatives

    Directory of Open Access Journals (Sweden)

    Hamzehloueian Mahshid

    2014-01-01

    Full Text Available The present study reports a systematic computational analysis of the two possible pathways, fused and bridged, for an intramolecular hetero Diels-Alder (IMHDA and an intramolecular 1,3-dipolar cycloaddition (IMDCA of 2-vinyloxybenzaldehyde derivatives. The potential energy surface analysis for both reactions is in agreement with experimental observations. The activation energies associated with the two regioisomeric channels in IMHDA reaction show that the bridged product is favored, although in IMDCA, the most stable TS results the fused product. The global electronic properties of fragments within each molecule were studied to discuss the reactivity patterns and charge transfer direction in the intramolecular processes. The asynchronicity of the bond formation and aromaticity of the optimized TSs in the Diels-Alder reaction as well as cycloaddition reaction were evaluated. Finally, 1H NMR chemical shifts of the possible regioisomers have been calculated using the GIAO method which of the most stable products are in agreement with the experimental data in the both reaction.

  4. A theoretical study on the reaction pathways and the mechanism of 1,3- dipolar cycloaddition of vinyl acetylene and methyl azide.

    Science.gov (United States)

    Siadati, Seyyed Amir; Mahboobifar, Ali; Nasiri, Ramin

    2014-01-01

    1,3-dipolar cycloaddition procedure is one of the most widely practiced methods in order to synthesize heterocyclic compounds. Although, it seems very simple, but, there are numerous precursors of heterocyclic molecules who have more than one positions to react with a 1,3-dipole species. As a result, while using a precursor with more than one position for reaction, it is probable to synthesize several products with different structures. This paper studies all possible interactions of vinyl acetylene, which has two positions for reaction, with methyl azide. This reaction could lead to the emergence of any 1,3-dipolar cycloaddition products. Our ultimate goal is to help researchers to find out how precursors containing both carbon-carbon double, and the triple bonds interact with 1,3- dipolar species. The present study used the DFT calculations at B3LYP/6-311++G(3df,pd) level to check all probable interactions between vinyl acetylene and methyl azide, and determined Potential Energy Surface, and optimized all species.

  5. Guiding plant virus particles to integrin-displaying cells

    Science.gov (United States)

    Hovlid, Marisa L.; Steinmetz, Nicole F.; Laufer, Burkhardt; Lau, Jolene L.; Kuzelka, Jane; Wang, Qian; Hyypiä, Timo; Nemerow, Glen R.; Kessler, Horst; Manchester, Marianne; Finn, M. G.

    2012-05-01

    Viral nanoparticles (VNPs) are structurally regular, highly stable, tunable nanomaterials that can be conveniently produced in high yields. Unmodified VNPs from plants and bacteria generally do not show tissue specificity or high selectivity in binding to or entry into mammalian cells. They are, however, malleable by both genetic and chemical means, making them useful scaffolds for the display of large numbers of cell- and tissue-targeting ligands, imaging moieties, and/or therapeutic agents in a well-defined manner. Capitalizing on this attribute, we modified the genetic sequence of the Cowpea mosaic virus (CPMV) coat protein to display an RGD oligopeptide sequence derived from human adenovirus type 2 (HAdV-2). Concurrently, wild-type CPMV was modified via NHS acylation and Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to attach an integrin-binding cyclic RGD peptide. Both types of particles showed strong and selective affinity for several different cancer cell lines that express RGD-binding integrin receptors.Viral nanoparticles (VNPs) are structurally regular, highly stable, tunable nanomaterials that can be conveniently produced in high yields. Unmodified VNPs from plants and bacteria generally do not show tissue specificity or high selectivity in binding to or entry into mammalian cells. They are, however, malleable by both genetic and chemical means, making them useful scaffolds for the display of large numbers of cell- and tissue-targeting ligands, imaging moieties, and/or therapeutic agents in a well-defined manner. Capitalizing on this attribute, we modified the genetic sequence of the Cowpea mosaic virus (CPMV) coat protein to display an RGD oligopeptide sequence derived from human adenovirus type 2 (HAdV-2). Concurrently, wild-type CPMV was modified via NHS acylation and Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) chemistry to attach an integrin-binding cyclic RGD peptide. Both types of particles showed strong and selective affinity

  6. 1, 3-Dipolar cycloaddition reactions: Synthesis of 5-benzyl-1-(2',4'-dibromophenyl)-3-(4"-substituted phenyl)-3a,4,6,6a-tetrahydro-1, 5-pyrrolo[3,4-]pyrazole-4,6-dione derivatives

    Indian Academy of Sciences (India)

    Manpreet Kaur; Baldev Singh; Baljit Singh

    2013-11-01

    1,3-Dipolar cycloaddition of nitrilimines 3 with -benzyl maleimide 4 has provided 5-benzyl-1-(2',4'-dibromophenyl)-3-(4"-substituted phenyl)-3a,4,6,6a-tetrahydro-1,5-pyrrolo[3,4-]pyrazole-4,6-dione derivatives 5 in excellent yield as the only isomer through a concerted pathway.

  7. [3+2] Cycloadditions of 1-halo-1-nitroethenes with (Z-C-(3,4,5-trimethoxyphenyl-N-methyl-nitrone as regio- and stereocontrolled source of novel bioactive compounds: preliminary studies

    Directory of Open Access Journals (Sweden)

    Radomir Jasiński

    2016-07-01

    Full Text Available Preliminary experiments shows, that [3+2] cycloadditions reactions proceeds with full regioselectivity and high stereoselectivity. In consequence, 3,4-trans-2-methyl-3-(3,4,5-trimethoxyphenyl-4-halo-4-nitroisoxazolidines are forming as predominantly (or sole products. Additionally, prognosis for the synthesized compounds to be potential ingredients of drugs is good.

  8. One-Pot Three-Step Synthesis of 1,2,3-Triazoles by Copper-Catalyzed Cycloaddition of Azides with Alkynes formed by a Sonogashira Cross-Coupling and Desilylation

    Science.gov (United States)

    Friscourt, Frédéric; Boons, Geert-Jan

    2010-01-01

    A microwave-assisted one-pot, three-step Sonogashira cross coupling-desilylation-cycloaddition sequence was developed for the convenient preparation of 1,4-disubstituted 1,2,3-triazoles starting from a range of halides, acyl chlorides, ethynyltrimethylsilane and azides. PMID:20942390

  9. 1,3-Dipolar cycloadditions of ethoxycarbonyl-nitrile benzylimine and synthesis of ß-amino acids. Synthesis and reactions of ethyl 2-chloro-2-ethoxyacetate and 2-chloro-2-ethoxyacetylchloride

    DEFF Research Database (Denmark)

    Bach, K.K.; El-Seedi, H.R.; Jensen, H.M.;

    1994-01-01

    The principles of 1,2-cyano-hydroxylation of olefins were applied to the preparation of 1,2-cyano-amines. The dipole component of this cycloaddition was nitrile imines, which formed pyrazolines with olefins. Ring cleavage was accomplished by thermolysis of 3-carboxypyrazolines, which gave 1,2-cya...

  10. Synthesis of ferrocenyl-substituted 1,3-dithiolanes via [3 + 2]-cycloadditions of ferrocenyl hetaryl thioketones with thiocarbonyl S-methanides

    Science.gov (United States)

    Hamera-Fałdyga, Róża; Linden, Anthony; Heimgartner, Heinz

    2016-01-01

    Summary Ferrocenyl hetaryl thioketones react smoothly with in situ generated thiocarbonyl S-methanides to give 1,3-dithiolanes. In the case of aromatic S-methanides, the sterically more crowded 4,4,5,5-tetrasubstituted 1,3-dithiolanes (2-CH2 isomers) were formed as sole products. The reactions with cycloaliphatic S-methanides led to mixtures of 2-CH2 and 5-CH2 isomers with the major component being the sterically more crowded 2-CH2 isomers. The preferred formation of the latter products is explained by the assumption that the formal [3 + 2]-cycloadducts were formed via a stepwise reaction mechanism with a stabilized 1,5-diradical as a key intermediate. The complete change of the reaction mechanism toward the concerted [3 + 2]-cycloaddition was observed in the reaction of a sterically crowded cycloaliphatic thiocarbonyl ylide with ferrocenyl methyl thioketone. PMID:27559392

  11. Conversion of actual flue gas CO 2 via cycloaddition to propylene oxide catalyzed by a single-site, recyclable zirconium catalyst

    KAUST Repository

    Kelly, Michael J.

    2017-06-12

    A reusable zirconium-based catalyst for the cycloaddition of CO2 to propylene oxide (PO) was prepared by the surface organometallic chemistry (SOMC) methodology. Accordingly, well-defined amounts of the ZrCl4·(OEt2)2 precursor were grafted on the surface of silica dehydroxylated at 700°C (SiO2-700) and at 200°C (SiO2-200) in order to afford surface coordination compounds with different podality and chemical environment. The identity of the surface complexes was thoroughly investigated by FT-IR, elemental microanalysis and solid state NMR and applied as a recoverable and reusable heterogeneous catalyst for the title reaction using pure CO2 and flue gas samples from a cement factory. The observed catalytic activity for the isolated zirconium complexes is rationalized by means of systematic DFT calculations.

  12. Niobium(v) chloride and imidazolium bromides as efficient dual catalyst systems for the cycloaddition of carbon dioxide and propylene oxide

    KAUST Repository

    Wilhelm, Michael E.

    2014-02-19

    The application of niobium(v) chloride and several imidazolium bromides as catalyst systems for the cycloaddition of propylene oxide (PO) with carbon dioxide to propylene carbonate (PC) is reported. A set of 31 different imidazolium bromides has been synthesized with varying substituents at all five imidazolium ring atoms, of which 17 have not been reported before. The impact of different substitution patterns (steric and electronic changes and solubility in PO) at the imidazolium ring on the catalytic activity was investigated. The optimisation of the catalyst structure allows for the valorisation of carbon dioxide under mild reaction conditions with high reaction rates in very good yield and selectivity for PC. This journal is © the Partner Organisations 2014.

  13. Synthetic scope and DFT analysis of the chiral binap–gold(I complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

    Directory of Open Access Journals (Sweden)

    María Martín-Rodríguez

    2013-11-01

    Full Text Available The 1,3-dipolar cycloaddition between glycine-derived azlactones with maleimides is efficiently catalyzed by the dimeric chiral complex [(Sa-Binap·AuTFA]2. The alanine-derived oxazolone only reacts with tert-butyl acrylate giving anomalous regiochemistry, which is explained and supported by Natural Resonance Theory and Nucleus Independent Chemical Shifts calculations. The origin of the high enantiodiscrimination observed with maleimides and tert-butyl acrylate is analyzed using DFT computed at M06/Lanl2dz//ONIOM(b3lyp/Lanl2dz:UFF level. Several applications of these cycloadducts in the synthesis of new proline derivatives with a 2,5-trans-arrangement and in the preparation of complex fused polycyclic molecules are described.

  14. Rhodium(III)-catalyzed N-nitroso-directed C-H addition to ethyl 2-oxoacetate for cycloaddition/fragmentation synthesis of indazoles.

    Science.gov (United States)

    Chen, Jinsen; Chen, Pei; Song, Chao; Zhu, Jin

    2014-10-27

    Rh(III) -catalyzed N-nitroso-directed CH addition to ethyl 2-oxoacetate allows subsequent construction of indazoles, a privileged heterocycle scaffold in synthetic chemistry, through the exploitation of reactivity between the directing group and installed group. The formal [2+2] cycloaddition/fragmentation reaction pathway identified herein, a unique reactivity pattern hitherto elusive for the N-nitroso group, emphasizes the importance of forward reactivity analysis in the development of useful CH functionalization-based synthetic tools. The synthetic utility of the protocol is demonstrated with the synthesis of a tricyclic-fused ring system. The diversity of covalent linkages available for the nitroso group should enable the extension of the genre of reactivity reported herein to the synthesis of other types of heterocycles.

  15. Enantioselective 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines to unsaturated nitriles catalyzed by NiII-Pigiphos.

    Science.gov (United States)

    Milosevic, Sandra; Togni, Antonio

    2013-10-04

    The asymmetric 1,3-dipolar cycloaddition reaction of C,N-cyclic azomethine imines with small unsaturated nitriles using a dicationic Ni(II) complex containing the chiral triphosphine ligand bis{(R)-1-[(Sp)-2-(diphenylphosphino)ferrocenyl]ethyl}cyclohexylphosphine [(R,Sp)-Pigiphos] as a catalyst has been developed. A variety of new chiral cyanopyrazolidines were obtained regio- and diastereoselectively in good to excellent yields with moderate to excellent enantioselectivities. Thus, N-benzoylimino-3,4-dihydro-6-methylisoquinolinium betaine (1a) reacts at RT with acrylonitrile in the presence of 1-5 mol % catalyst to afford 3,4-trans-1-benzoyl-4-cyano-2,3-(tetrahydroisoquinoline)tetrahydropyrazole (2a) in up to 84% yield and 98% ee. The regio- and stereoselectivity were confirmed in the case of compound 2a and 3,4-trans-1-benzoyl-4-cyano-2,3-(6-bromotetrahydroisoquinoline)tetrahydropyrazole (2e) by X-ray crystallography.

  16. DFT study of the mechanism and stereoselectivity of the 1,3-dipolar cycloaddition between pyrroline-1-oxide and methyl crotonate

    Indian Academy of Sciences (India)

    Khadija Marakchi; Rachida Ghailane; Oum Kaltoum Kabbaj; Najia Komiha

    2014-01-01

    A theoretical study of the regio- and stereoselectivities of the 1,3-dipolar cycloaddition reaction between methyl crotonate and pyrroline-1-oxide has been carried out using density functional theory (DFT) at the B3LYP/6-31G(d) level of theory. The reaction has been followed by performing transition state optimization, calculations of intrinsic reaction coordinate and activation energies; the molecular mechanism of the reactions is concerted and asynchronous. The regio- and exo/endo-selectivity have been explained in terms of frontier molecular orbital interactions, local and global electrophilicity and nucleophilicity indices and an analysis of theWiberg bond indices in the transition state. The FMO analysis and DFT-based reactivity indices showed that the regioselectivity of this reaction is controlled by the HOMOdipole-LUMOdipolarophile interaction. The activation parameters indicated favoured endo approach along the meta-pathway in agreement with the experimental results.

  17. Niobium(v) chloride and imidazolium bromides as efficient dual catalyst systems for the cycloaddition of carbon dioxide and propylene oxide

    KAUST Repository

    Wilhelm, Michael E.

    2014-01-01

    The application of niobium(v) chloride and several imidazolium bromides as catalyst systems for the cycloaddition of propylene oxide (PO) with carbon dioxide to propylene carbonate (PC) is reported. A set of 31 different imidazolium bromides has been synthesized with varying substituents at all five imidazolium ring atoms, of which 17 have not been reported before. The impact of different substitution patterns (steric and electronic changes and solubility in PO) at the imidazolium ring on the catalytic activity was investigated. The optimisation of the catalyst structure allows for the valorisation of carbon dioxide under mild reaction conditions with high reaction rates in very good yield and selectivity for PC. This journal is © the Partner Organisations 2014.

  18. Cu-MCM-41 nanoparticles: An efficient catalyst for the synthesis of 5-substituted 1-tetrazoles via [3+2] cycloaddition reaction of nitriles and sodium azide

    Indian Academy of Sciences (India)

    Mohammad Abdollahi-Alibeik; Ali Moaddeli

    2016-01-01

    [3+2] cycloaddition reaction of various types of nitriles and sodium azide (NaN3) were studied in the presence of nano-sized Cu-MCM-41 as an efficient recoverable heterogeneous catalyst. Nano-sized Cu-MCM-41 mesoporous molecular sieves with various Si/Cu molar ratios were synthesized by direct insertion of metal ions at room temperature. The textural properties of the materials have been studied by means of XRD, FTIR, SEM and TEM techniques. Catalytic behavior of Cu-MCM-41 was also investigated by pyridine absorption and potentiometric titration. The reactions data verified characterization results and show that Cu-MCM-41 with Si/Cu molar ratio of 20 has considerably better catalytic activity compared to the other molar ratios. To investigate reusability, the catalyst was recovered by simple filtration and reused for several cycles with consistent activity.

  19. Theoretical insights into the cycloaddition reaction mechanism between ketenimine and methyleneimine: An alternative approach to the formation of pyrazole and imidazole

    Indian Academy of Sciences (India)

    Nana Wang; Xiaojun Tan; Weihua Wang; Fangfang Wang; Ping Li

    2016-02-01

    The cycloaddition reaction mechanism between interstellar molecules, ketenimine and methyleneimine, has been systematically investigated employing the second-order Møller-Plesset perturbation theory (MP2) method in order to better understand the reactivity of nitrogenous cumulene ketenimine with the C=N double bond compound methyleneimine. Geometry optimizations and vibrational analyses have been performed for the stationary points on the potential energy surfaces of the system. Calculations show that five-membered cyclic carbene intermediates could be produced through pericyclic reaction processes between ketenimine and methyleneimine. Through the subsequent hydrogen transfer processes, carbene intermediates can be isomerized to the pyrazole and imidazole compounds, respectively. The present study is helpful to understand the formation of prebiotic species in interstellar space.

  20. Ultrasonic Synthesis, Molecular Structure and Mechanistic Study of 1,3-Dipolar Cycloaddition Reaction of 1-Alkynylpyridinium-3-olate and Acetylene Derivatives

    Directory of Open Access Journals (Sweden)

    Asmaa Aboelnaga

    2016-06-01

    Full Text Available Regioselectively, ethyl propiolate reacted with 1-(propergyl-pyridinium-3-olate to give two regioisomers; ethyl 4-oxo-8-(prop-2-ynyl-8-aza-bicyclo(3.2.1octa-2,6-diene-6-carboxylate 4, ethyl 2-oxo-8-(prop-2-ynyl-8-aza-bicyclo(3.2.1octa-3,6-diene-6-carboxylate 5 as well as ethyl 2,6-dihydro-6-(prop-2-ynylfuro(2,3-cpyridine-3-carboxylate 6. The obtained compounds were identified by their spectral (IR, mass and NMR data. Moreover, DFT quantum chemical calculations were used to study the mechanism of the cycloaddition reaction. The regioselectivity was explained using transition state calculations, where the calculations agreed with the formation of products 4 and 5 in almost the same ratio. The reaction was also extended for diphenylaceylene as dipolarophile to give only two products instead of three.