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  • 51.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Exploring the Molecular Behavior of Carbohydrates by NMR Spectroscopy: Shapes, motions and interactions2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Carbohydrates are essential biomolecules that decorate cell membranes and proteins in organisms. They are important both as structural elements and as identification markers. Many biological and pathogenic processes rely on the identification of carbohydrates by proteins, thereby making them attractive as molecular blueprints for drugs. This thesis describes how NMR spectroscopy can be utilized to study carbohydrates in solution at a molecular level. This versatile technique facilitates for investigations of (i) shapes, (ii) motions and (iii) interactions.

    A conformational study of an E. coli O-antigen was performed by calculating atomic distances from NMR NOESY experiments. The acquired data was utilized to validate MD simulations of the LPS embedded in a membrane. The agreement between experimental and calculated data was good and deviations were proven to arise from spin-diffusion. In another study presented herein, both the conformation and the dynamic behavior of amide side-chains linked to derivatives of D-Fucp3N, a sugar found in the O-antigen of bacteria, were investigated. J-couplings facilitated a conformational analysis and 13C saturation transfer NMR experiments were utilized to measure rate constants of amide cis-trans isomerizations.

    13C NMR relaxation and 1H PFG diffusion measurements were carried out to explore and describe the molecular motion of mannofullerenes. The dominating motions of the mannofullerene spectral density were found to be related to pulsating motions of the linkers rather than global rotational diffusion. The promising inhibition of Ebola viruses identified for a larger mannofullerene can thus be explained by an efficient rebinding mechanism that arises from the observed flexibility in the linker.

    Molecular interactions between sugars and caffeine in water were studied by monitoring chemical shift displacements in titrations. The magnitude of the chemical shift displacements indicate that the binding occurs by a face to face stacking of the aromatic plane of caffeine to the ring plane of the sugar, and that the interaction is at least partly driven by solvation effects. Also, the binding of a Shigella flexneri serotype Y octasaccharide to a bacteriophage Sf6 tail spike protein was investigated. This interaction was studied by 1H STD NMR and trNOESY experiments. A quantitative analysis of the STD data was performed employing a newly developed method, CORCEMA-ST-CSD, that is able to simulate STD data more accurately since the line broadening of protein resonances are accounted for in the calculations.

  • 52.
    Eriksson, Kristofer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development and Applications of Surface-Confined Transition Metal Complexes: Heterogeneous Catalysis and Anisotropic Particle Surfaces2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main focus of this thesis has been directed towards developing novel surface-confined transition metal complexes for applications in heterogeneous catalysis and for the preparation of anisotropic particle surfaces. The first part describes the heterogenization of a homogeneous transition metal-based catalyst tetraphenyl cobalt porphyrin (CoTPP) on silicon wafers and on silica particles. The activity in hydroquinone oxidation for the silica particle-immobilized CoTPPs was found to be increased 100-fold compared to its homogeneous congener whereas the silicon wafer-immobilized CoTPPs achieved lower activity due to the formation of clusters of catalyst molecules on the support surface as detected with atomic force microscopy (AFM). The second part of this thesis describes the development and characterization of anisotropic particle-surfaces by electrochemical site-specific oxidation of surface-confined thiols. Reactive patches or gold gradients could be obtained on the particle surfaces depending on the type of working electrode used and on the electrolyte composition. The particle surface functionalities were characterized with X-ray photoelectron spectroscopy (XPS) and the particle-surface-confined patches and gradients were conjugated with proteins to obtain fluorescence for investigation using fluorescence microscopy. Gold-functionalized siliceous mesocellular foams were further demonstrated to be highly efficient and selective catalysts in the cycloisomerization of 4-alkynoic acids to lactones. The final part of this thesis describes the preparation and characterization of palladium nanoparticles heterogenized in the pores of siliceous mesocellular foam. The nanoparticles were analyzed with transmission electron microscopy (TEM) and found to have a size of 1-2 nm. Primary- and secondary benzylic- and allylic alcohols were oxidized by the heterogeneous palladium nanoparticles in high to excellent yields using air atmosphere as the oxygen source. The nanopalladium catalyst was used up to five times without any decrease in activity and the size of the nanoparticles was retained according to TEM.

  • 53.
    Eriksson, Kristofer
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Johansson, Lars Erik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Göthelid, Emmanuelle
    Department of Physics and Astroniomy Uppsala University.
    Nyholm, Leif
    Department of Chemistry, Uppsala Univeristy.
    Oscarsson, Sven
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Manufacturing of Anisotropic Particles by Site Specific Oxidation of Thiols2012In: Journal of Materials Chemistry, ISSN 0959-9428, E-ISSN 1364-5501, Vol. 22, no 16, p. 7681-7683Article in journal (Refereed)
    Abstract [en]

    A novel method for the manufacturing of functional anisotropic particles based on an inexpensive and straightforward electrochemical approach is presented. The method enables large-scale manufacturing of anisotropic particles as well as fabrication of multifunctional beads which may be used in the design of barcodes for multiplex diagnostics.

  • 54.
    Eriksson, Kristofer
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palmgren, Pal
    Nyholm, Leif
    Oscarsson, Sven
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Electrochemical Synthesis of Gold and Protein Gradients on Particle Surfaces2012In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 28, no 28, p. 10318-10323Article in journal (Refereed)
    Abstract [en]

    A straightforward, versatile approach to the production of protein gradients on planar and spherical particle surfaces is described. The method is based on the spatially controlled oxidation of thiolated surfaces by Au(III) ions generated via the electrochemical oxidation of a gold electrode in a phosphate-buffered saline solution (10 mM PBS, pH 7.2, 150 mM NaCl). Because the gold electrode is in direct contact with the thiolated surfaces, the released Au(III) ions, which are present as Au(III) chloride complexes, give rise to the formation of a surface gradient of Au(I)-thiolate complexes depending on the local redox potential given by the local Au(III) concentration. As is shown on the basis of the use of X-ray photoelectron spectroscopy and fluorescently labeled proteins, the Au(I)-thiolate complexes can subsequently be functionalized with thiolated proteins, yielding surface density protein gradients on micrometer-sized nonconducting polymer beads as well as linear Au(I)-thiolate gradients on planar silicon surfaces.

  • 55.
    Fontana, Carolina
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Weintraub, Andrej
    Karolinska Institute.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Facile Structural Elucidation of Glycans Using NMR Spectroscopy Data and the Program CASPER: Application to the O-Antigen Polysaccharide of Escherichia coli O1552013In: ChemPlusChem, ISSN 2192-6506, Vol. 78, no 11, p. 1327-1329Article in journal (Refereed)
    Abstract [en]

    The program CASPER was successfully employed to rapidly elucidate a new O-antigen polysaccharide structure (obtained from a strain of Escherichia coli serogroup O155), using solelyunassigned NMR spectroscopy data as input information. Thus, what is considered the most tedious and time-consuming part of the structural elucidation process has been reduced from several hours (or even days) of manual interpretation to about four minutes of automated analysis.

  • 56.
    Fransson, Ann-Britt L.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Deracemization of Functionalized Alcohols via Combined Ruthenium and Enzyme Catalysis2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The major part of this thesis describes the synthesis of enantiopure alcohols and diols by combining ruthenium-catalyzed racemization or epimerization and lipase-catalyzed asymmetric transformations. A minor part of this thesis is focused on ruthenium-catalyzed redox reactions for transfer hydrogenation of 1,3-cycloalkanediketones.

    Kinetic resolution of racemic γ-hydroxy acid derivatives was performed via Pseudomonas cepacia lipase (PS-C)-catalyzed transesterification. γ-Hydroxy esters and γ-hydroxy amides were studied showing in higher selec-tivity and yields for the γ-hydroxy amides. The enzyme PS-C tolerates both variation in the chain length and different functionalities giving good to high enantioselectivity. Combining enzymatic kinetic resolution with a ruthenium-catalyzed racemization led to a dynamic kinetic resolution (DKR). The use of 2,4-dimethyl-3-pentanol as a hydrogen source to suppress ketone formation in the dynamic kinetic resolution increased the yields of the acetate product. The synthetic utility of this procedure was illustrated by the practical synthesis of the γ-lactone (R)-5-methyltetrahydrofuran-2-one.

    A distereoselective transformation of cis/trans-1,3-cyclohexandiol using Candida antarctica lipase B (CALB)-catalyzed transesterification was of interest. Desymmetrization of cis-1,3-cyclohexanediol to the (R-monoacetate was successfully accomplished. Enantiopure (R,R)-diacetate was obtained from the (R)-monoacetate in a DYKAT process at room tem-perature. Metal- and enzyme-catalyzed transformation of cis/trans-1,3-cyclohexanediol using PS-C, gives a high diastereoselectivity for cis-diacetate. The (S)-mono-acetate was obtained from cis-diacetate by CALB-catalyzed hydrolysis. In addition, it was shown, by the use of deuterium-labeling that intramolecular acyl migration does not occur in the transformation of cis-monoacetate to the cis-diacetate.

    Ruthenium-catalyzed transfer hydrogenation of 1,3-cyclohexanedione under microwave heating was developed as an efficient and fast method for the preparation of 1,3-cycloalkandiols.

  • 57.
    Frigell, Jens
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of O-linked Carbasugar Analogues of Galactofuranosides and N-linked Neodisaccharides2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, carbohydrate mimicry is investigated through the syntheses of carbohydrate analogues and evaluation of their inhibitory effects on carbohydrate-processing enzymes.

    Galactofuranosides are interesting structures because they are common motifs in pathogenic microorganisms but not found in mammals. M.tuberculosis, responsible for the disease tuberculosis, has a cell wall containing a repeating unit of alternating (1→5)- and (1→6)-linked β-D-galactofuranosyl residues. Synthetic inhibitors of the enzymes involved in the biosynthesis of the cell wall could find great therapeutic use.

    The first part of this thesis describes the first synthesis of the hydrolytically stable carbasugar analogue of galactofuranose, 4a-carba-β-D-Galf, and the synthetic work of synthesising β-linked pseudodisaccharides containing carba-Galf, which were tested for glycosyltransferease inhibitory activity. The pseudodisaccharide carba-Galf-(β1→5)-carba-Galf was found to be a moderate inhibitor of the glycosyltransferase GlfT2 of M.tuberculosis. The thesis also describes how a general method towards biologically relevant α-linked carba-Galf ethers was developed.

    The final part of this thesis is focussed on the formation of nitrogen-linked monosaccharides without the participation of the anomeric centre. Such a mode of coupling is called tail-to-tail neodisaccharide formation. The couplings of carbohydrate derivatives via the Mitsunobu reaction are successfully reported herein. The method describes the key introduction of an allylic alcohol in the electrophile and the subsequent functionalisation of the alkene to obtain the neodisaccharide. Two synthesised neodisaccharides presented in this thesis have been sent to be tested for glycosidase inhibitory activity.

  • 58.
    Frigell, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cumpstey, Ian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    First synthesis of 4a-carba-beta-D-galactofuranose2007In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 48, no 52, p. 9073-9076Article in journal (Refereed)
  • 59.
    Frigell, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cumpstey, Ian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of carbadisaccharide mimics of galactofuranosides2009In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 50, no 36, p. 5142-5144Article in journal (Refereed)
  • 60.
    Gemma, Emiliano
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of Oligosaccharides for Interaction Studies with Various Lectins2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, the syntheses of oligosaccharides for interaction studies with various lectins are described. The first section reports the syntheses of tetra, tri- and disaccharides corresponding to truncated versions of the glucosylated arm of Glc1Man9(GlcNAc)2, found in the biosynthesis of N-glycans. The thermodynamic parameters of their interaction with calreticulin, a lectin assisting and promoting the correct folding of newly synthesised glycoproteins, were established by isothermal titration calorimetry. In the second section, a new synthetic pathway leading to the same tetra- and trisaccharides is discussed. Adoption of a convergent strategy and of a different protecting group pattern resulted in significantly increased yields of the target structures. The third section describes the syntheses of a number of monodeoxy-trisaccharides related to the above trisaccharide Glc-α-(1→3)-Man-α-(1→2)-Man-α-OMe. Differentsynthetic approaches were explored and the choice of early introduction of the deoxy functionality proved the most beneficial. In the last section, the synthesis of spacer-linked LacNAc dimers as substrates for the lectins galectin-1 and -3 is presented. This synthesis was realized by glycosidation of a number diols with peracetylated LacNAc-oxazoline. Pyridinium triflate was tested as a new promoter, affording the target dimers in high yields. This promoter in combination with microwave irradiation gave even higher yields and also shortened the reaction times.

  • 61.
    Ghosh, Raju
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lindstedt, Erik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Jalalian, Nazli
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Room Temperature, Metal-Free Arylation of Aliphatic Alcohols2014In: ChemistryOpen, ISSN 2191-1363, Vol. 3, no 2, p. 54-57Article in journal (Refereed)
    Abstract [en]

    Diaryliodonium salts are demonstrated as efficient arylating agents of aliphatic alcohols under metal-free conditions. The reaction proceeds at room temperature within 90min to give alkyl aryl ethers in good to excellent yields. Aryl groups with electron-withdrawing substituents are transferred most efficiently, and unsymmetric iodonium salts give chemoselective arylations. The methodology has been applied to the formal synthesis of butoxycaine.

  • 62.
    Ghosh, Raju
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Metal-Free Synthesis of N-Aryloxyimides and Aryloxyamines2014In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 16, no 6, p. 1830-1832Article in journal (Refereed)
    Abstract [en]

    N-Hydroxyphthalimide and N-hydroxysuccinimide have been arylated with diaryliodonium salts to provide N-aryloxyimides in excellent yields in short reaction times. A novel hydrolysis under mild and hydrazine-free conditions yielded aryloxyamines, which are valuable building blocks in the synthesis of oxime ethers and benzofurans.

  • 63.
    Gigant, Nicolas
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Access to Cinnamyl Derivatives from Arenes and Allyl Esters by a Biomimetic Aerobic Oxidative Dehydrogenative Coupling2014In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 16, no 6, p. 1664-1667Article in journal (Refereed)
    Abstract [en]

    An efficient biomimetic aerobic oxidative dehydrogenative alkenylation of arenes with allyl esters is presented. The reaction proceeds under an ambient pressure of oxygen with relatively low catalyst loading of palladium acetate, employing catalytic amounts of electron-transfer mediators (ETMs). This study represents a new environmentally friendly method for the synthesis of cinnamyl derivatives.

  • 64.
    Gigant, Nicolas
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Aerobic Direct C-H Arylation of Nonbiased Olefins2014In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 16, no 17, p. 4432-4435Article in journal (Refereed)
    Abstract [en]

    An efficient ligand-promoted biomimetic aerobic oxidative dehydrogenative cross-coupling between arenes and nonbiased olefins is presented. Acridine as a ligand was found to significantly enhance the rate, the yield, and the scope of the reaction under ambient oxygen pressure, providing a variety of alkenylarenes via an environmentally friendly procedure.

  • 65.
    Gigant, Nicolas
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Aerobic Double Dehydrogenative Cross Coupling between Cyclic Saturated Ketones and Simple Arenes2014In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 20, p. 5890-5894Article in journal (Refereed)
    Abstract [en]

    The synthesis of 3-aryl-2-cyclohexenones is a topic of current interest as they are not only privileged structures in bioactive molecules, but they are also relevant feedstocks for the synthesis of substituted phenols or anilines, which are ubiquitous structural elements both in drug design and medicinal chemistry. A simple and sustainable one-pot aerobic double dehydrogenative reaction under mild conditions for the introduction of arenes in the -position of cyclic ketones has been developed. Starting from the corresponding saturated ketone, this reaction sequence proceeds under relatively low Pd catalyst loading and involves catalytic amounts of electron-transfer mediators (ETMs) under ambient oxygen pressure.

  • 66.
    González Miera, Greco
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bermejo Gómez, Antonio
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Chupas, Peter J.
    Martín-Matute, Belén
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Chapman, Karena W.
    Platero-Prats, Ana E.
    Topological Transformation of a Metal–Organic Framework Triggered by Ligand Exchange2017In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 56, no 8, p. 4576-4583Article in journal (Refereed)
    Abstract [en]

    Here we describe the topological transformation of the pores of a new framework in the bio-MOF-100 family (dia-c) into the known isomer (lcs) by doubling the pore volume, which occurs during postsynthesis modifications. During this transformation, reassembling of the metal–organic framework (MOF) building blocks into a completely different framework occurs, involving breaking/forming of metal–ligand bonds. MOF crystallinity and local structure are retained, as determined by powder X-ray diffraction (PXRD) and pair distribution function (PDF) analyses, respectively. We exploited the inherent dynamism of bio-MOF-100 by coupling chemical decorations of the framework using solvent-assisted ligand exchange to the topological change. Following this method and starting from the pristine dense dia-c phase, open lcs-bio-MOF-100 was prepared and functionalized in situ with an iridium complex (IrL). Alternatively, the dia-c MOF could be modified with wide-ranging amounts of IrL up to ca. 50 mol %, as determined by solution 1H NMR spectroscopy, by tuning the concentration of the solutions used and with no evidence for isomer transformation. The single-site nature of the iridium complexes within the MOFs was assessed by X-ray absorption spectroscopy (XAS) and PDF analyses. Ligand exchanges occurred quantitatively at room temperature, with no need of excess of the iridium metallolinker.

  • 67.
    González Miera, Greco
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Martínez-Castro, Elisa
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Martín-Matute, Belén
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Acceptorless Alcohol Dehydrogenation: OH vs NH Effect in Bifunctional NHC–Ir(III) Complexes2017In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041Article in journal (Refereed)
    Abstract [en]

    Bifunctional complexes bearing N-heterocyclic carbene (NHC) ligands functionalized with hydroxy or amine groups were synthesized to measure the beneficial effect of different modes of metal–ligand cooperation in the acceptorless dehydrogenation of alcohols. In comparison to complexes with an amine moiety, hydroxy-functionalized iridium catalysts showed superior activity. In contrast to alcohols, 1,4-diols underwent cyclization to give the corresponding tetrahydrofurans without involving dehydrogenation processes. Mechanistic investigations to rationalize the “OH effect” in these types of complexes have been undertaken.

  • 68.
    Gustafson, Karl P. J.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lihammar, Richard
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Verho, Oscar
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Engström, Karin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Chemoenzymatic Dynamic Kinetic Resolution of Primary Amines Using a Recyclable Palladium Nanoparticle Catalyst Together with Lipases2014In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 79, no 9, p. 3747-3751Article in journal (Refereed)
    Abstract [en]

    A catalyst consisting of palladium nanoparticles supported on amino-functionalized siliceous mesocellular foam (Pd-AmP-MCF) was used in chemoenzymatic dynamic kinetic resolution (DKR) to convert primary amines to amides in high yields and excellent ee's. The efficiency of the nanocatalyst at temperatures below 70 degrees C enables reaction conditions that are more suitable for enzymes. In the present study, this is exemplified by subjecting 1-phenylethylamine (1a) and analogous benzylic amines to DKR reactions using two commercially available lipases, Novozyme-435 (Candida antartica Lipase B) and Amano Lipase PS-C1 (lipase from Burkholderia cepacia) as biocatalysts. The latter enzyme has not previously been used in the DKR of amines because of its low stability at temperatures over 60 degrees C. The viability of the heterogeneous Pd-AmP-MCF was further demonstrated in a recycling study, which shows that the catalyst can be reused up to five times.

  • 69.
    Hamark, Christoffer
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Landström, Jens
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    SEAL by NMR: Glyco-Based Selenium-Labeled Affinity Ligands Detected by NMR Spectroscopy2014In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 43, p. 13905-13908Article in journal (Refereed)
    Abstract [en]

    We report a method for the screening of interactions between proteins and selenium-labeled carbohydrate ligands. SEAL by NMR is demonstrated with selenoglycosides binding to lectins where the selenium nucleus serves as an NMR-active handle and reports on binding through Se-77 NMR spectroscopy. In terms of overall sensitivity, this nucleus is comparable to C-13 NMR, while the NMR spectral width is ten times larger, yielding little overlap in Se-77 NMR spectroscopy, even for similar compounds. The studied ligands are singly selenated bioisosteres of methyl glycosides for which straightforward preparation methods are at hand and libraries can readily be generated. The strength of the approach lies in its simplicity, sensitivity to binding events, the tolerance to additives and the possibility of having several ligands in the assay. This study extends the increasing potential of selenium in structure biology and medicinal chemistry. We anticipate that SEAL by NMR will be a beneficial tool for the development of selenium-based bioactive compounds, such as glycomimetic drug candidates.

  • 70. Harper, James K.
    et al.
    Tishler, Derek
    Richardson, David
    Lokvam, John
    Pendrill, Robert
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Solid-State NMR Characterization of the Molecular Conformation in Disordered Methyl alpha-L-Rhamnofuranoside2013In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 117, no 26, p. 5534-5541Article in journal (Refereed)
    Abstract [en]

    A combination of solid-state C-13 NMR tensor data and DFT computational methods is utilized to predict the conformation in disordered methyl alpha-L-rhamnofuranoside. This previously uncharacterized solid is found to be crystalline and consists of at least six distinct conformations that exchange on the kHz time scale. A total of 66 model structures were evaluated, and six were identified as being consistent with experimental C-13 NMR data. All feasible structures have very similar carbon and oxygen positions and differ most significantly in OH hydrogen orientations. A concerted rearrangement of OH hydrogens is proposed to account for the observed dynamic disorder. This rearrangement is accompanied by smaller changes in ring conformation and is slow enough to be observed on the NMR time scale due to severe steric crowding among ring substituents. The relatively minor differences in non-hydrogen atom positions in the final structures suggest that characterization of a complete crystal structure by X-ray powder diffraction may be feasible.

  • 71. He, Xibing
    et al.
    Hatcher, Elizabeth
    Eriksson, Lars
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    MacKerell, Alexander D., Jr.
    Bifurcated Hydrogen Bonding and Asymmetric Fluctuations in a Carbohydrate Crystal Studied via X-ray Crystallography and Computational Analysis2013In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, no 25, p. 7546-7553Article in journal (Refereed)
    Abstract [en]

    The structure of the O-methyl glycoside of the naturally occurring 6-O-[(R)-1-carboxyethyl]-alpha-D-galactopyranose, C10H18O8, has been determined by X-ray crystallography at 100 K, supplementing the previously determined structure obtained at 293 K (Acta Crystallogr. 1996, C52, 2285-2287). Molecular dynamics simulations of this glycoside were Performed in the crystal environment with different numbers of units cells included in the primary simulation system at both 100 and 293 K. The Calculated unit cell Parameters and the intramolecular geometries (bonds, angles, and dihedrals) agree well with experimental results. Atomic fluctuations, including B-factors and anisotropies, are in good agreement with respect to the relative values on an atom-by-atom basis. In addition, the fluctuations increase with increasing simulation system size, with the simulated values converging to values lower than those observed experimentally indicating that the simulation model is not accounting for all possible contributions to the experimentally observed B-factors, which may be related to either the simulation time scale or size. In the simulation's, the hydroxyl group of O7 is found to from bifurcated hydrogen bonds with O6 and O8 of an adjacent molecule, with the interactions dominated by the interaction HO7-O6 interaction. Quantum mechanical calculations support this observation.

  • 72.
    Ilchenko, Nadia O.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Novel Applications of Benziodoxole Reagents in the Synthesis of Organofluorine Compounds2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis concerns method development of new synthetic routes by applying electrophilic hypervalent iodine reagents, such as trifluoromethyl-benziodoxole (Togni reagent) and fluoro-benziodoxole. The first project involved the addition of an oxygen moiety and trifluoromethyl group across double and triple bonds (both groups derived from the hypervalent iodine reagent). We observed that electron donating substituents on the aromatic ring of the substrate accelerated the oxytrifluoromethylation reaction. This transformation was further expanded to halo-trifluoromethylation reaction of a vinyl silane substrate. We also developed a copper mediated cyanotrifluoromethylation reaction, which was accelerated by PCy3 additive. This transformation allowed for the creation of two new C-C bonds in a single addition reaction. The direct C-H trifluoromethylation reaction of quinones was achived using the Togni-reagent in the presence of B2pin2 additive. The intriguing additive effects of both B2pin2 and PCy3 inspired us to examine the mechanism of these transformations.

    Fluoro-benziodoxole is the fluoroiodane analogue of the trifluoromethylating Togni reagent. We developed a AgBF4 mediated geminal difluorination of styrenes using this fluoroiodine reagent. In this process one fluorine atom came from the fluoroiodane, while the other fluorine was derived from the tetrafluoroborate ion. A similar approach was applied for the 1,3-oxyfluorination and difluorination of cyclopropanes. Similarly, this fluorinative ring opening of unactivated cyclopropanes involved the introduction of an electrophilic fluorine atom from the fluoroiodane reagent and a nucleophilic one from the tetrafluoroborate ion. This reaction was extended to synthesis of 1,3-oxyfluorinated products. When alkenes reacted with the fluoro-benziodoxole reagent in the presence of palladium catalyst the iodofluorination reaction occurred.  Both the iodine and fluorine atoms were derived from the fluoroiodane reagent. The iodofluorination reaction with disubstituted and cyclic alkenes proceeded with high regio- and stereoselectivity.

  • 73.
    Ilchenko, Nadia O.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Tasch, Boris O. A.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabó, Kálmán J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mild Silver-Mediated Geminal Difluorination of Styrenes Using an Air- and Moisture-Stable Fluoroiodane Reagent2014In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 53, no 47, p. 12897-12901Article in journal (Refereed)
    Abstract [en]

    An air-and moisture-stable fluoroiodane in the presence of AgBF4 is suitable for selective geminal difluorination of styrenes under mild reaction conditions. One of the C-F bonds is formed by transfer of electrophilic fluorine from the hypervalent iodine reagent, while the other one arises from the tetrafluoroborate counterion of silver. Deuterium-isotope-labelling experiments and rearrangement of methyl styrene substrates suggest that the reaction proceeds through a phenonium ion intermediate.

  • 74.
    Jalalian, Nazli
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development and Applications of Hypervalent Iodine Compounds: Powerful Arylation and Oxidation Reagents2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The first part of this thesis describes the efficient synthesis of several hypervalent iodine(III) compounds. Electron-rich diaryliodonium salts have been synthesized in a one-pot procedure, employing mCPBA as the oxidant. Both symmetric and unsymmetric diaryliodonium tosylates can be isolated in high yields. An in situ anion exchange also enables the synthesis of previously unobtainable diaryliodonium triflates.

    A large-scale protocol for the synthesis of a derivative of Koser’s reagent, that is an isolable intermediate in the diaryliodonium tosylate synthesis, is furthermore described. The large-scale synthesis is performed in neat TFE, which can be recovered and recycled. This is very desirable from an environmental point of view.

    One of the few described syntheses of enantiopure diaryliodonium salts is discussed. Three different enantiopure diaryliodonium salts bearing electron-rich substituents are synthesized in moderate to high yields. The synthesis of these three salts shows the challenge in the preparation of electron-rich substituted unsymmetric salts.

    The second part of the thesis describes the application of both symmetric and unsymmetric diaryliodonium salts in organic synthesis. A metal-free efficient and fast method for the synthesis of diaryl ethers from diaryliodonium salts has been developed. The substrate scope is wide as both the phenol and the diaryliodonium salt can be varied. Products such as halogenated ethers, ortho-substituted ethers and bulky ethers, that are difficult to obtain with metal-catalyzed procedures, are readily prepared. The mild protocol allows arylation of racemization-prone a-amino acid derivatives without loss of enantiomeric excess.

    A chemoselectivity investigation was conducted, in which unsymmetric diaryliodonium salts were employed in the arylation of three different nucleophiles in order to understand the different factors that influence which aryl moiety that is transferred to the nucleophile.

  • 75.
    Jalalian, Nazli
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ishikawa, Eloisa E.
    Universidade de Sao Paulo, Instituto de Quimica.
    Silva Jr., Luiz F.
    Universidade de Sao Paulo, Instituto de Quimica.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Room temperature, metal-free synthesis of diaryl ethers with use of diaryliodonium salts2011In: Abstracts of Papers, 242nd ACS National Meeting & Exposition, Denver, CO, United States, August 28-September 1, 2011, American Chemical Society , 2011Conference paper (Other academic)
    Abstract [en]

    Diaryl ethers are common structural features in numerous natural products and biol. active compds.  Despite more than a century of immense focus on finding efficient synthetic routes to this compd. class, diaryl ethers remain difficult to obtain.  Routes that are catalytic in copper have been developed, but high catalyst loadings, excess reagents, elevated temps. and long reaction times are still needed.  Pd-catalyzed cross-couplings of phenols and aryl halides at temps. up to 100 °C have recently been reported to give high yields of diaryl ethers.  Diaryliodonium salts are non-toxic alternatives to transition metals in the synthesis of diaryl ethers and we have recently developed effective synthetic routes to these salts.  Herein we report a fast, high-yielding synthesis of diaryl ethers.  The reaction conditions are mild, metal-free, and avoid the use of halogenated solvents, additives, or excess reagents.  Precautions to avoid air or moisture are not needed.  The scope includes ortho- and halo-substituted diaryl ethers, which are difficult to obtain by metal-catalyzed protocols .

  • 76.
    Jalalian, Nazli
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Asymmetric α-arylation of carbonyl compounds with chiral diaryliodonium salts2009In: Abstracts of Papers, 238th ACS National Meeting, Washington, DC, United States, August 16-20, 2009, Washington, D.C.: American Chemical Society , 2009Conference paper (Other academic)
  • 77.
    Jalalian, Nazli
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Design and asymmetric synthesis of chiral diaryliodonium salts2010In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 66, no 31, p. 5793-5800Article in journal (Refereed)
    Abstract [en]

    The application of chiral hypervalent iodine reagents in asymmetric synthesis is highly desirable, as the reagents are metal-free, environmentally benign and employed under mild conditions. Three chiral diaryliodonium salts have been designed to provide chemoselectivity and asymmetric induction in asymmetric alpha-phenylation of carbonyl compounds. The synthetic routes to the selected targets are detailed herein, together with a structural investigation into the diastereoselectivity of the alkylation process.

  • 78.
    Jalalian, Nazli
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of Koser’s Reagent and Derivatives2013In: Organic Syntheses, ISSN 0078-6209, Vol. 90, p. 1-9Article in journal (Refereed)
  • 79.
    Janson, Pär
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Oxidative Trifluoromethylation and other Functionalization Reactions of Alkenes and Alkynes2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis concerns the use of various potent oxidants in organic synthesis. The main focus is directed at selectively introducing trifluoromethyl groups into compounds containing double or triple bonds. All reactions proceed under mild conditions and can in most cases be performed on the bench-top.

    We have developed three different procedures for transformations of activated alkenes and alkynes as well as quinones. In paper I the selective introduction of a trifluoromethyl group together with an oxygen functionality to double and triple bonds is demonstrated.

    Paper II is focused on the related chemoselective cyanotrifluoromethylation in which a cyano group is added instead of the oxygen functionality.

    Paper III describes a new procedure for C–H trifluoromethylation of quinones. Our studies on the mechanistic aspects of the above reactions are described in Paper IV. In these studies we investigated the ligand and substituent effects in Cu-catalyzed reactions.

    Paper V is focused on a conceptually new palladium-catalyzed allylic C–H acyloxylation of olefins under oxidative conditions. The procedure uses an inexpensive, safe and environmentally benign oxidant, sodium perborate, which is activated with acetic anhydride.

  • 80.
    Jiang, Tuo
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium(II)-Catalyzed Oxidative Carbocyclization: Stereoselective Formation of C–C and C–B Bonds2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Transition metal catalysis has emerged as one of the most versatile methods for the selective formation of carbon–carbon and carbon–heteroatom bonds. In particular, oxidative carbon–carbon bond forming reactions have been widely studied due to their atom economic feature. This thesis has been focused on the development of new palladium(II)-catalyzed carbocyclization reactions under oxidative conditions.

    The first part of the thesis describes the palladium(II)-catalyzed oxidative carbocyclization-borylation and -arylation of enallenes. In these reactions, the (σ-alkyl)palladium(II) intermediate, which was shown previously to undergo β-hydride elimination, could be trapped in situ by organoboron reagents (B2pin2 and arylboronic acids) to form new carbon–boron and carbon–carbon bonds. Through these two protocols, a range of borylated and arylated carbocycles were obtained as single diastereomers in high yields.

    The second part deals with a palladium(II)-catalyzed oxidative diarylative carbocyclization of enynes. The reaction was proposed to start with a syn-arylpalladation of an alkyne, followed by insertion of the coordinated alkene. Subsequent arylation afforded a series of valuable diarylated tetrahydrofuran and tetrahydropyran products.

    The final part of the thesis advances the previously developed palladium(II)-catalyzed oxidative carbocyclization-borylation of enallenes in an enantioselective manner. C2-symmetric chiral phosphoric acids were used as the novel co-catalyst to trigger the enantioselective formation of intramolecular carbon–carbon bonds. By using this chiral anion strategy, a number of enallenes were converted to the borylated carbocycles with high to excellent enantioselectivity.

  • 81.
    Johansson, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ruthenium(II) Polypyridyl Complexes: Applications in Artificial Photosynthesis2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Molecular mimics of PS II, which consist of a photosensitizer linked to electron acceptors/donors, are attractive candidates for the conversion of solar energy into chemical energy. Several different classes of sensitizers have been studied and among these, ruthenium(II) polypyridyl complexes continue to attract major attention.

    The first part of this thesis presents the photophysical properties, stereochemistry, and general synthesis of ruthenium(II) polypyridyl complexes based on 2,2´-bipyridyl and 2,2´:6´,2´´-terpyridyl ligands. The second part deals with ruthenium(II) polypyridyl complexes linked to electron acceptors (benzoquinone, naphthalene diimide) and electron donors (phenothiazine, tyrosine, manganese complexes). Functionalized 2,2´-bipyridines and 2,2´:6´,2´´-terpyridines were synthesized and used in the stepwise assembly of the chromophore-quencher complexes. These were fully characterized and the redox properties were studied by cyclic and differential pulse voltammetry. The intramolecular charge-separated states formed after light excitation of the ruthenium(II) unit were observed by time-resolved absorption and EPR spectroscopy.

    In the third part of this thesis, the synthesis and photophysical properties of a novel class of bistridentate ruthenium(II) polypyridyl complexes based on bipyridyl-pyridyl methane ligamds are discussed. The solution structures of the homoleptic and heteroleptic complexes were studied by 2D NMR techniques. The X-ray structure of one of the homoleptic complexes has been solved. The effect on the excited state lifetime for these ruthenium(II) complexes compared to the parent [Ru(tpy)2]2+ is discussed. Finally, in one of the heteroleptic complexes an interesting reversible linkage iomerization was observed that could be induced either electrochemically or chemically.

  • 82.
    Johansson, Tommy
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Studies on Transformations of H-Phosphonates into DNA Analogues Containing P-S or P-C Bonds2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, mechanistic and synthetic studies on transformations of H-phosphonates into DNA analogues containing P-S or P-C bonds are described.

    Configurational stability of dinucleoside H-phosphonates and the stereochemical course of their sulfurisation in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) were investigated. In light of these studies, the reported stereoselective sulfurisation of dinucleoside H-phosphonates and benzoylphosphonates in the presence of DBU was proved to be incorrect.

    Efficient protocols for the synthesis of new nucleotide analogues with non-ionic C-phosphonate internucleotide linkages were developed. The synthesis of dinucleoside 2-pyridylphosphonates was successfully performed by a DBU-promoted reaction of H-phosphonate diesters with N-methoxypyridinium salts. The thio analogues, 2-pyridyl- and 4-pyridyl phosphonothioate diesters, could be obtained by modifying the reactions developed for their oxo counterparts. Dinucleoside 3-pyridylphosphonates were prepared via a palladium(0)-catalysed cross coupling strategy that could be extended also to the synthesis of nucleotide analogues with metal-complexing properties, i.e. terpyridyl- and bipyridylphosphonate derivatives.

    Oligonucleotides modified with pyridylphosphonate internucleotide linkages have been prepared and preliminary studies on their hybridisation properties and resistance towards enzymatic degradation were performed.

    Finally, nucleotidic units for the incorporation of pyridylphosphonate groups at the 5’-terminus of oligonucleotides were designed. Condensations of such units with a suitably protected nucleoside afforded after oxidation the expected dinucleoside (3’-5’)-phosphates with pyridylphosphonate monoester functions at the 5’-ends.

  • 83.
    Johnston, Eric
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    New Tools for Green Catalysis: Studies on a Biomimetic Hybrid Catalyst and a Novel Nanopalladium Catalyst2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The first part of this thesis describes an improved synthetic route to hybrid (hydroquinone-Schiff base)cobalt catalysts. Preparation of the 5-(2,5-hydroxyphenyl)salicylaldehyde building block was improved by altering the protective groups of the hydroquinone (HQ) starting material. Both protection and deprotection could be carried out under mild conditions, resulting in high yields. By optimizing the reaction conditions of the Suzuki cross-coupling, an efficient and inexpensive synthetic route with a good overall yield was developed.

    The second part describes the use of the hybrid catalyst as an electron transfer mediator (ETM) in the palladium-catalyzed aerobic carbocyclization of enallenes. By covalently linking the HQ to the cobalt Schiff-base complex the reaction proceeded at lower temperatures with a five-fold increase of the reaction rate compared to the previously reported system.

    The third part describes the application of the hybrid catalyst in the biomimetic aerobic oxidation of secondary alcohols. Due to the effi­ciency of the intramolecular electron transfer, the hybrid catalyst allowed for a lower catalytic loading and milder reaction conditions compared to the previous separate-component system. Benzylic alcohols as well as aliphatic alcohols were oxidized to the corresponding ketones in excellent yield and selectivity using this methodology.

    The fourth part describes the synthesis and characterization of highly dispersed palladium nanoparticles supported on aminopropyl-modified siliceous mesocellular foam. The Pd nanocatalyst showed excellent activity for the aerobic oxidation of a wide variety of alcohols under air atmosphere. Moreover, the catalyst can be recycled several times without any decrease in activity or leaching of the metal into solution.

    Finally, the fifth part describes the application of the Pd nanocatalyst in transfer hydrogenations and Suzuki coupling reactions. The catalyst was found to be highly efficient for both transformations, resulting in chemoselective reduction of various alkenes as well as coupling of a variety of aryl halides with various boronic acids in excellent yields. Performing the latter reaction under microwave irradiation significantly increased the reaction rate, compared to conventional heating. However, no significant increase in reaction rate was observed for the transfer hydrogenations, under microwave heating.

  • 84.
    Jonsson, Hanna
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Exploring the structure of oligo- and polysaccharides: Synthesis and NMR spectroscopy studies2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A deeper understanding of the diversity of carbohydrates and the many applications of oligo- and polysaccharides found in nature are of high interest. Many of the processes involving carbohydrates affect our everyday life. This thesis is based on six papers all contributing to an extended perspective of carbohydrate property and functionality. An introduction to carbohydrate chemistry together with a presentation of selected carbohydrate synthesis and analysis methods introduces the reader to the research field. The first paper is an NMR spectroscopy reinvestigation of the structures of the O-antigens from the lipopolysaccharides (LPS) of Shigella dysenteriae type 3 and Escherichia coli O124. The repeating units were concluded to be built of identical branched pentasaccharides now with the correct anomeric configurations. Paper II is a structural investigation of the O-antigen from the LPS of E. coli O74 which is built of branched tetrasaccharide repeating units including the uncommon monosaccharide d-Fuc3NAc. Paper III is a conformational study of a rhamnose derivative, using NMR spectroscopy and X-ray crystallography. The benzoyl ester group positioned at C4 prefers an “eclipsed” conformation in the crystal as well as in solution. The use of site-specifically 13C-labeled compounds in conformational studies is discussed in Papers IV and V. The disaccharide α-L-Rhap-(1→2)-α-L-Rhap-OMe was synthesized together with two 13C-isotopologues and studied with NMR spectroscopy to give seven J-couplings related to torsion angles φ and ψ. The trisaccharide α-L-Rhap-(1→2)[α-L-Rhap-(1→3)]-α-L-Rhap-OMe was synthesized with 13C-labeling at two positions which presented a solution to a problem of overlapping signals in the 1H NMR spectrum. The site-specific labeling also facilitated the measurement of two 3JCC and two 2JCH coupling constants. Finally, chapter 6 gives a short introduction to glycosynthase chemistry and discusses the synthesis of α-glycosyl fluorides. A novel cyclic heptasaccharide was synthesized from α-laminariheptaosyl fluoride using a mutant of the enzyme laminarase 16A and subsequently analyzed by NMR spectroscopy.

  • 85.
    Kadow, Maria
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry. Ernst Moritz Arndt Universitat Greifswald, Germany.
    Balke, Kathleen
    Willetts, Andrew
    Bornscheuer, Uwe T.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Functional assembly of camphor converting two-component Baeyer-Villiger monooxygenases with a flavin reductase from E-coli2014In: Applied Microbiology and Biotechnology, ISSN 0175-7598, E-ISSN 1432-0614, Vol. 98, no 9, p. 3975-3986Article in journal (Refereed)
    Abstract [en]

    The major limitation in the synthetic application of two-component Baeyer-Villiger monooxygenases was addressed by identifying the 28-kDa flavin-reductase Fre from Escherichia coli as a suitable supplier of reduced FMN for these enzymes. Coexpression of Fre with either 2,5- or 3,6-diketocamphane monooxygenase from Pseudomonas putida NCIMB 10007 significantly enhanced the conversion of camphor and norcamphor serving as representative ketones. With purified enzymes, full conversion was achieved, while only slight amounts of product were formed in the absence of this flavin reductase. Fusion of the genes of Fre and DKCMOs into single open reading frame constructs resulted in unstable proteins exhibiting flavin reducing, but poor oxygenating activity, which led to overall decreased conversion of camphor.

  • 86.
    Kalek, Marcin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of C(sp2)-P bonds by palladium-catalyzed reactions: Mechanistic investigations and synthetic studies2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focuses on synthetic and mechanistic aspects of palladium-catalyzed C(sp2)-P bond-forming reactions, with the aim to develop mild and efficient methods for the synthesis of biologically active phosphorus compounds, e.g. DNA analogs.

    The first part of the thesis is devoted to detailed mechanistic investigations of the palladium-catalyzed C-P cross-coupling reaction, in order to fully understand the underlying chemistry and by rational design of the reaction conditions, improve the overall efficiency of the process and broaden its applicability. In particular influence of palladium coordination by different anions on the rate of ligand substitution and reductive elimination steps of the reaction was studied. It was found that coordination of acetate ion results in unprecedented acceleration of both of the mechanistic steps, what leads to remarkable shortening of the overall reaction times. In-depth kinetic investigations enabled to ascribe the observed effects to ability of the acetate ion to act as a bidentate ligand for palladium. This causes considerable alternation of the reaction mechanism, comparing to the reaction involving halide-containing complexes, and results in significant rate increase.

    Based on the above mechanistic studies an efficient method for the synthesis of arylphosphonates, using substoichiometric amounts of inorganic acetate additive and reduced amount of catalyst, was developed.

    In the next part of the thesis, efforts to further enhance the palladium-catalyzed cross-coupling efficiency by using a microwave-assisted synthesis are described. These explorations resulted in a successful development of two protocols, one for a cross-coupling of H-phosphonates and the other for H,H-phosphinates, under the microwave heating conditions. Application of this energy source resulted in extremely short reaction times, measured in minutes.

    The final chapter of this thesis deals with studies on palladium-catalyzed SN2’ propargylic substitution reaction with phosphorus nucleophiles, which leads to allene products. Efficient procedure for the synthesis of allenylphosphonates and related compounds was developed. The method enables full control of stereochemistry in the allene moiety and at the asymmetric phosphorus center. Some conclusions on the mechanism of the reaction were also drawn.

  • 87.
    Karlsson, Erik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Catalysts for Oxygen Production and Utilization: Closing the Oxygen Cycle: From Biomimetic Oxidation to Artificial Photosynthesis2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes the development and study of catalysts for redox reactions, which either utilize oxygen or hydrogen peroxide for the purpose of selectively oxidizing organic substrates, or produce oxygen as the necessary byproduct in the production of hydrogen by artificial photosynthesis.

    The first chapter gives a general introduction about the use of environmentally friendly oxidants in the field of organic synthesis, and about the field of artificial photosynthesis. The second chapter describes a computational study of the mechanism of palladium-catalyzed oxidative carbohydroxylation of allene-substituted conjugated dienes. The proposed mechanism, which was supported by DFT calculations, involves an unusual water attack on a (π-allyl)palladium complex. The third chapter describes a computational study of the oxidation of unfunctionalized hydrocarbons, ethers and alcohols with hydrogen peroxide, catalyzed by methyltrioxorhenium (MTO). The mechanism was found to proceed via rate-limiting hydride abstraction followed by hydroxide transfer in a single concerted, but highly asynchronous, step as shown by intrinsic reaction coordinate (IRC) scans. The fourth chapter describes the use of a new hybrid (hydroquinone-Schiff base)cobalt catalyst as electron transfer mediator (ETM) in the palladium-catalyzed aerobic carbocyclization of enallenes. Covalently linking the two ETMs gave a fivefold rate increase compared to the use of separate components. The fifth chapter describes an improved synthetic route to the (hydroquinone-Schiff base)cobalt catalysts. Preparation of the key intermediate 5-(2,5-hydroxyphenyl)salicylaldehyde was improved by optimization of the key Suzuki coupling and change of protecting groups from methyl ethers to easily cleaved THP groups. The catalysts could thus be prepared in good overall yield from inexpensive starting materials.

    Finally, the sixth chapter describes the preparation and study of two catalysts for water oxidation, both based on ligands containing imidazole groups, analogous to the histidine residues present in the oxygen evolving complex (OEC) and in many other metalloenzymes. The first, ruthenium-based, catalyst was found to catalyze highly efficient water oxidation induced by visible light. The second catalyst is, to the best of our knowledge, the first homogeneous manganese complex to catalyze light-driven water oxidation.

  • 88.
    Kjellgren, Johan
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Employment of Palladium Pincer Complex Catalysts and Lewis Acids for Synthesis and Transformation of Organometallic Compounds2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis is mainly focused on the development of new palladium catalyzed transformations using so-called “pincer” complexes. These complexes were applied as catalysts in two important areas of organometallic chemistry: substitution of propargylic substrates by dimetallic reagents; and allylation of aldehydes and imines by allylstannanes. In addition, this thesis includes studies on Lewis acid mediated cyclization reactions of allylsilanes with aldehydes.

    Pincer complex catalyzed substitution of various propargylic substrates could be achieved under mild conditions using tin and silicon based dimetallic reagents to obtain propargyl- and allenylstannanes and silanes. The regioselectivity of the substitution reaction strongly depends on the steric and electronic effects of the propargylic substrate. According to our mechanistic studies the key intermediate of the reaction is an organostannane (or silane) coordinated pincer complex. DFT modeling studies on the transfer of the trimethylstannyl functionality to the propargylic substrate revealed a novel mechanism, which is based on the unique topology of the pincer-complex catalysts.

    Our further studies showed that palladium pincer complexes can be employed as efficient catalysts for electrophilic allylic substitution of allylstannanes with aldehyde and imine substrates. In contrast to previous applications for electrophilic allylic substitutions via bis-allylpalladium complexes, this reaction involves mono-allylpalladium intermediates which were observed by 1H-NMR spectroscopy.

    The last chapter of this thesis is focused on Lewis-acid mediated cyclization of hydroxy functionalized allylsilanes, which afford tetrahydropyran derivatives with a high stereoselectivity.

  • 89.
    Kullberg, Martin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Studies on nucleoside H-phosphonoselenoate chemistry and chalcogen exchange reaction between P(V) and P(III) compounds2005Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, the chemistry of compounds containing P-Se bonds has been studied. As a new addition to this class of compounds, H-phosphonoselenoate monoesters, have been introduced and two synthetic pathways for their preparation have been developed.

    The reactivity of H-phosphonoselenoate monoesters towards a variety of condensing agents has been studied. From these, efficient conditions for the synthesis of H-phosphonoselenoate diesters have been developed. The produced diesters have subsequently been used in oxidative transformations, which gave access to the corresponding P(V) compounds, e.g. dinucleoside phosphoroselenoates or dinucleoside phosphoroselenothioates.

    Furthermore, a new selenizing agent, triphenyl phosphoroselenoate, has been developed for selenization of P(III) compounds. This reagent has high solubility in organic solvents and was found to convert phosphite triesters and H-phosphonate diesters efficiently into the corresponding phosphoroselenoate derivatives.

    The selenization of P(III) compounds with triphenyl phosphoroselenoate proceeds through a selenium transfer reaction. A computational study was performed to gain insight into a mechanism for this reaction. The results indicate that the transfer of selenium or sulfur from P(V) to P(III) compounds proceeds most likely via an X-philic attack of the P(III) nucleophile on the chalcogen of the P(V) species. For the transfer of oxygen, the reaction may also proceed via an edge attack on the P=O bond.

  • 90. Küpper, Frithjof C.
    et al.
    Feiters, Martin C.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kaiho, Tatsuo
    Yanagida, Shozo
    Zimmermann, Michael B.
    Carpenter, Lucy J.
    Luther, George W.
    Lu, Zunli
    Jonsson, Mats
    Kloo, Lars
    Purple fumes: the importance of iodine2013In: Science in School, ISSN 1818-0353, E-ISSN 1818-0361, no 27, p. 10p. 45-53Article in journal (Other academic)
  • 91.
    Laine, Tanja M.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development of Ruthenium Catalysts for Water Oxidation2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An increasing global energy demand requires alternative fuel sources. A promising method is artificial photosynthesis. Although, the artificial processes are different from the natural photosynthetic process, the basic principles are the same, i.e. to split water and to convert solar energy into chemical energy. The energy is stored in bonds, which can at a later stage be released upon combustion. The bottleneck in the artificial systems is the water oxidation. The aim of this research has been to develop catalysts for water oxidation that are stable, yet efficient. The molecular catalysts are comprised of organic ligands that ultimately are responsible for the catalyst structure and activity. These ligands are often based on polypyridines or other nitrogen-containing aromatic compounds. This thesis describes the development of molecular ruthenium catalysts and the evaluation of their ability to mediate chemical and photochemical oxidation of water. Previous work from our group has shown that the introduction of negatively charged groups into the ligand frameworks lowers the redox potentials of the metal complexes. This is beneficial as it makes it possible to drive water oxidation with [Ru(bpy)3]3+-type oxidants (bpy = 2,2’-bipyridine), which can be photochemically generated from the corresponding [Ru(bpy)3]2+ complex. Hence, all the designed ligands herein contain negatively charged groups in the coordination site for ruthenium.

    The first part of this thesis describes the development of two mononuclear ruthenium complexes and the evaluation of these for water oxidation. Both complexes displayed low redox potentials, allowing for water oxidation to be driven either chemically or photochemically using the mild one-electron oxidant [Ru(bpy)3]3+.

    The second part is a structure–activity relationship study on several analogues of mononuclear ruthenium complexes. The complexes were active for water oxidation and the redox potentials of the analogues displayed a linear relationship with the Hammet σmeta parameter. It was also found that the complexes form high-valent Ru(VI) species, which are responsible for mediating O–O bond formation.

    The last part of the thesis describes the development of a dinuclear ruthenium complex and the catalytic performance for chemical and photochemical water oxidation. It was found that the complex undergoes O–O bond formation via a bridging peroxide intermediate, i.e. an I2M–type mechanism.

  • 92.
    Larsson, Andreas
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis, structure and conformation of oligo- and polysaccharides2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Carbohydrates are a complex group of biomolecules with a high structural diversity. Their almost omnipresent occurrence has generated a broad field of research in both biology and chemistry. This thesis focuses on three different aspects of carbohydrate chemistry, synthesis, structure elucidation and the conformational analysis of carbohydrates.

    The first paper describes the synthesis of a penta- and a tetrasaccharide related to the highly branched capsular polysaccharide from Streptococcus pneumoniae type 37. In the second paper, the structure of the O-antigenic repeating unit from the lipopolysaccharide of E. coli 396/C1 was determined along with indications of the structure of the biological repeating unit. In addition, its structural and immunological relationship with E. coli O126 is discussed. In the third paper, partially protected galactopyranosides were examined to clarify the origin of an intriguing 4JHO,H coupling, where a W-mediated coupling pathway was found to operate. In the fourth paper, the conformation of methyl a-cellobioside is studied with a combination of molecular dynamics simulations and NMR spectroscopy. In addition to the expected syn-conformation, detection and quantification of anti-ø and anti-ψ conformers was also possible.

  • 93.
    Larsson, Johanna M.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Transition metal-catalyzed allylic and vinylic functionalization: Method development and mechanistic investigations2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The use of small molecule building blocks in, for example, pharmaceutical research and new material development, creates a need for new and improved organic synthesis methods. The use of transition metals as mediators and catalysts opens up new reaction pathways that have made the synthesis of completely new compounds possible as well as greatly improved the synthetic routes to known compounds.

    Herein, the development of new metal-mediated and catalyzed reactions for construction of vinylic and allylic carbon-carbon and carbon-heteroatom bonds is described.  The use of iodonium salts as coupling partners in Pd-catalyzed Heck type reactions with alkenes is shown to improve the current substrate scope. Results from a mechanistic study indicate that the reaction proceeds via high oxidation state palladium intermediates.

    The use of IIII reagents is also believed to facilitate a PdII/PdIV catalytic cycle in allylic silylation of alkenes using (SiMe3)2, which, to the best of our knowledge, is the first method developed for metal-catalyzed allylic C-H silylation.

    The same silyl-source, (SiMe3)2, has previously been used in a Pd-catalyzed allylic substitution reaction in which allylic silanes are formed from allylic alcohols. A detailed mechanistic investigation of this reaction is described in which by-products as well as intermediates, including the resting state of the catalyst, are identified using 1H, 11B, 19F and 29Si NMR spectroscopy. Kinetic experiments are performed that give information about the turn-over limiting step and the mechanism of the analogous borylation using B2pin2 is also investigated. Insights from this study further made it possible to improve the stereoselectivity of this reaction.

    Additionally, a new method for Cu-mediated trifluoromethylation of allylic halides is presented in which linear products are formed exclusively from both linear and branched allylic substrates at room temperature.  Identification of allylic fluorides as by-products during the reaction also led to the development of a similar Cu-mediated reaction for the fluorination of allylic halides.

  • 94. Li, Jia-Qi
    et al.
    Andersson, Pher G.
    Stockholm University, Faculty of Science, Department of Organic Chemistry. University of KwaZulu-Natal, South Africa.
    Room temperature and solvent-free iridium-catalyzed selective alkylation of anilines with alcohols2013In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 49, no 55, p. 6131-6133Article in journal (Refereed)
    Abstract [en]

    A bidentate iridium NHC-phosphine complex has been developed and applied to the N-monoalkylation of aromatic amines with a wide range of primary alcohols and to the N-heterocyclization of amino alcohols. This reaction resulted in high isolated product yields, even at room temperature and under solvent-free conditions.

  • 95.
    Liao, Rongzhen
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Quantum Chemical Cluster Modeling of Enzymatic Reactions2010Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The Quantum chemical cluster approach has been shown to be quite powerful and efficient in the modeling of enzyme active sites and reaction mechanisms. In this thesis, the reaction mechanisms of several enzymes have been investigated using the hybrid density functional B3LYP. The enzymes studied include four dinuclear zinc enzymes, namely dihydroorotase, N-acyl-homoserine lactone hydrolase, RNase Z, and human renal dipeptidase, two trinuclear zinc enzymes, namely phospholipase C and nuclease P1, two tungstoenzymes, namely formaldehyde ferredoxin oxidoreductase and acetylene hydratase, aspartate α-decarboxylase, and mycolic acid cyclopropane synthase. The potential energy profiles for various mechanistic scenarios have been calculated and analyzed. The role of the metal ions as well as important active site residues has been discussed.

      In the cluster approach, the effects of the parts of the enzyme that are not explicitly included in the model are taken into account using implicit solvation methods.

      For all six zinc-dependent enzymes studied, the di-zinc bridging hydroxide has been shown to be capable of performing nucleophilic attack on the substrate. In addition, one, two, or even all three zinc ions participate in the stabilization of the negative charge in the transition states and intermediates, thereby lowering the barriers.

      For the two tungstoenzymes, several different mechanistic scenarios have been considered to identify the energetically most feasible one. For both enzymes, new mechanisms are proposed.

      Finally, the mechanism of mycolic acid cyclopropane synthase has been shown to be a direct methyl transfer to the substrate double bond, followed by proton transfer to the bicarbonate.

      From the studies of these enzymes, we demonstrate that density functional calculations are able to solve mechanistic problems related to enzymatic reactions, and a wealth of new insight can be obtained.

  • 96.
    Lihammar, Richard
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Enzyme- and Transition Metal-Catalyzed Asymmetric Transformations: Application of Enzymatic (D)KR in Enantioselective Synthesis2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dynamic kinetic resolution (DKR) is a powerful method for obtaining compounds with high optical purity. The process relies on the combination of a kinetic resolution with an in situ racemization. In this thesis, a combination of an immobilized hydrolase and a transition metal-based racemization catalyst was employed in DKR to transform racemic alcohols and amines into enantioenriched esters and amides, respectively.

    In the first part the DKR of 1,2-amino alcohols with different rings sizes and N-protecting groups is described. We showed that the immobilization method used to support the lipase strongly influenced the stereoselectivity of the reaction.

    The second part deals with the DKR of C3-functionalized cyclic allylic alcohols affording the corresponding allylic esters in high yields and high ee’s. The protocol was also extended to include carbohydrate derivatives, leading to inversion of a hydroxyl substituted chiral center on the carbohydrate.

    The third part focuses on an improved method for obtaining benzylic primary amines. By using a novel, recyclable catalyst composed of Pd nanoparticles on amino-functionalized mesocellular foam, DKR could be performed at 50 °C. Moreover, Lipase PS was for the first time employed in the DKR of amines.

    In the fourth part DKR was applied in the total synthesis of Duloxetine, a compound used in the treatment of major depressive disorder. By performing a six-step synthesis, utilizing DKR in the enantiodetermining step, Duloxetine could be isolated in an overall yield of 37% and an ee >96%.

    In the final part we investigated how the enantioselectivty of reactions catalyzed by Candida Antarctica lipase B for δ-substituted alkan-2-ols are influenced by water. The results showed that the enzyme displays much higher enantioselectivity in water than in anhydrous toluene. The effect was rationalized by the creation of a water mediated hydrogen bond in the active site that helps the enzyme form enantiodiscriminating binding modes.

  • 97.
    Lihammar, Richard
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Rönnols, Jerk
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Epimerization of Glycal Derivatives by a Cyclopentadienylruthenium Catalyst: Application to Metalloenzymatic DYKAT2014In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 45, p. 14756-14762Article in journal (Refereed)
    Abstract [en]

    Epimerization of a non-anomeric stereogenic center in carbohydrates is an important transformation in the synthesis of natural products. In this study an epimerization procedure of the allylic alcohols of glycals by cyclopentadienylruthenium catalyst 1 is presented. The epimerization of 4,6-O-benzylidene-D-glucal 4 in toluene is rapid, and an equlibrium with its D-allal epimer 5 is established within 5min at room temperature. Exchange rates for allal and glucal formation were determined by 1D H-1 EXSY NMR experiments to be 0.055s(-1) and 0.075s(-1), respectively. For 4-O-benzyl-L-rhamnal 8 the epimerization was less rapid and four days of epimerization was required to achieve equilibration of the epimers at room temperature. The epimerization methodology was subsequently combined with acylating enzymes in a dynamic kinetic asymmetric transformation (DYKAT), giving stereoselective acylation to the desired stereoisomers 12, 13, and 15. The net effect of this process is an inversion of a stereogenic center on the glycal, and yields ranging from 71% to 83% of the epimer were obtained.

  • 98.
    Lind, Maria E. S.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Quantum Chemical Modeling of Asymmetric Enzymatic Reactions2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Computational methods are very useful tools in the study of enzymatic reactions, as they can provide a detailed understanding of reaction mechanisms and the sources of various selectivities. In this thesis, density functional theory has been employed to examine four different enzymes of potential importance for biocatalytic applications. The enzymes considered are limonene epoxide hydrolase, soluble epoxide hydrolase, arylmalonate decarboxylase and phenolic acid decarboxylase. Besides the reaction mechanisms, the enantioselectivities in three of these enzymes have also been investigated in detail. In all studies, quite large quantum chemical cluster models of the active sites have been used. In particular, the models have to account for the chiral environment of the active site in order to reproduce and rationalize the experimentally observed selectivities.

    For both epoxide hydrolases, the calculated enantioselectivities are in good agreement with experiments. In addition, explanations for the change in stereochemical outcome for the mutants of limonene epoxide hydrolase, and for the observed enantioconvergency in the soluble epoxide hydrolase are presented.

    The reaction mechanisms of the two decarboxylases are found to involve the formation of an enediolate- or a quinone methide intermediate, supporting thus the main features of the proposed mechanisms in both cases. For arylmalonate decarboxylase, an explanation for the observed enantioselectivity is also presented.

    In addition to the obtained chemical insights, the results presented in this thesis demonstrate that the quantum chemical cluster approach is indeed a valuable tool in the field of asymmetric biocatalysis.

  • 99.
    Lindberg, Bo G.
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Merritt, Eleanor A.
    Rayl, Melanie
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Liu, Chenxiao
    Parmryd, Ingela
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Faye, Ingrid
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Immunogenic and Antioxidant Effects of a Pathogen-Associated Prenyl Pyrophosphate in Anopheles gambiae2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, p. e73868-Article in journal (Refereed)
    Abstract [en]

    Despite efficient vector transmission, Plasmodium parasites suffer great bottlenecks during their developmental stages within Anopheles mosquitoes. The outcome depends on a complex three-way interaction between host, parasite and gut bacteria. Although considerable progress has been made recently in deciphering Anopheles effector responses, little is currently known regarding the underlying microbial immune elicitors. An interesting candidate in this sense is the pathogen-derived prenyl pyrophosphate and designated phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP), found in Plasmodium and most eubacteria but not in higher eukaryotes. HMBPP is the most potent stimulant known of human V gamma 9V delta 2 T cells, a unique lymphocyte subset that expands during several infections including malaria. In this study, we show that V(Y)9V delta 2 T cells proliferate when stimulated with supernatants from intraerythrocytic stages of Plasmodium falciparum cultures, suggesting that biologically relevant doses of phosphoantigens are excreted by the parasite. Next, we used Anopheles gambiae to investigate the immune-and redox-stimulating effects of HMBPP. We demonstrate a potent activation in vitro of all but one of the signaling pathways earlier implicated in the human V(Y)9V delta 2 T cell response, as p38, JNK and PI3K/Akt but not ERK were activated in the A. gambiae 4a3B cell line. Additionally, both HMBPP and the downstream endogenous metabolite isopentenyl pyrophosphate displayed antioxidant effects by promoting cellular tolerance to hydrogen peroxide challenge. When provided in the mosquito blood meal, HMBPP induced temporal changes in the expression of several immune genes. In contrast to meso-diaminopimelic acid containing peptidoglycan, HMBPP induced expression of dual oxidase and nitric oxide synthase, two key determinants of Plasmodium infection. Furthermore, temporal fluctuations in midgut bacterial numbers were observed. The multifaceted effects observed in this study indicates that HMBPP is an important elicitor in common for both Plasmodium and gut bacteria in the mosquito.

  • 100.
    Lindstedt, Erik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Metal-Free O- and C-Arylation with Diaryliodonium Salts2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis concerns the development of metal-free applications using diaryliodonium salts. The first project describes an arylation protocol of allylic and benzylic alcohols in aqueous media. The method proceeds under mild conditions and the ether products were obtained in moderate to good yields. The methodology was also expanded to include arylation of phenols, giving diaryl ethers in good to excellent yields. In the second project, an arylation method that included a wider range of aliphatic alcohols was developed. The scope of accessible alkyl aryl ethers was studied and included a comparative study of phenylation and nitrophenylation of various alcohols. Finally, a formal metal-free synthesis of butoxycain was performed, illustrating the applicability of the developed method.

    The third project focused on the limitations and side reactions occurring in Chapter 2 and 3. First, an approach to access symmetric diaryl ethers via arylation of hydroxide was presented. This reaction gave rise to a number of side products, which we hypothesized to originate from aryne-type intermediates. A mechanism for the formation of these side products was suggested, supported by trapping and deuterium labeling experiments.

    Oxidation of the alcohol to the corresponding ketone was also observed and the mechanism of this interesting side reaction was investigated. The latter was suggested to proceed via an intramolecular oxidation without the involvement of radicals or arynes.

    The fourth project covers a method to synthesize highly sterically congested alkyl aryl ethers via arylation of tertiary alcohols using diaryliodonium salts. The method displayed a broad scope of tertiary alcohols and was also suitable for fluorinated alcohols.

    The final project detailed in this thesis deals with C-arylation with diaryliodonium salts, showcasing nitroalkanes as well as a nitro ester as suitable nucleophiles for metal-free arylation. 

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