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  • 251.
    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.

  • 252.
    Frigell, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cumpstey, Ian
    Carbasugar analogues of galactofuranose: α-O-linked derivativesManuscript (preprint) (Other academic)
    Abstract [en]

    Using an indirect method, we have synthesised α-linked carbasugar analogues of galactofuranosides for the first time. Opening of a β-talo configured carbasugar 1,2-epoxide by alcohol nucleophiles under Lewis acidic conditions proceeded with very good regioselectivity to give α-talo configured C-1-substituted ethers with OH-2 free. Inversion of configuration at OH-2 by an oxidation–reduction sequence gave the α-galacto configured carbahexofuranose C-1 ethers. A carbadisaccharide corresponding to the Galf(α1→3)Manp substructure from Apodus deciduus galactomannan was synthesised to exemplify the method.

  • 253.
    Frigell, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cumpstey, Ian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Carbasugar analogues of galactofuranosides: alpha-O-linked derivatives2010In: BEILSTEIN J ORG CHEM, ISSN 1860-5397, Vol. 6, p. 1127-1131Article in journal (Refereed)
    Abstract [en]

    Using an indirect method, we have synthesised alpha-linked carbasugar analogues of galactofuranosides for the first time. Ring opening of a beta-talo configured carbasugar 1,2-epoxide by alcohol nucleophiles under Lewis acidic conditions proceeded with very good regioselectivity to give alpha-talo configured C1-substituted ethers with a free OH-group at the C2 position. Inversion of configuration at C2 by an oxidation-reduction sequence gave the alpha-galacto configured carbahexofuranose C1 ethers. A carbadisaccharide corresponding to the Galf(alpha 1 -> 3)Manp substructure from Apodus deciduus galactomannan was synthesised to exemplify the method.

  • 254.
    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)
  • 255.
    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)
  • 256.
    Frigell, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Eriksson, Lars
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Cumpstey, Ian
    Carbasugar analogues of galactofuranosides: β-O-linked derivativesManuscript (preprint) (Other academic)
    Abstract [en]

    A selectively protected carbasugar analogue of β-galactofuranose was synthesised from glucose using ring-closing metathesis as the key step. The carbasugar was converted into an α-galacto configured 1,2-epoxide, which was an effective electrophile in Lewis acid catalysed coupling reactions with alcohols. The epoxide was opened with regioselective attack at C-1 to give β-galacto configured C-1 ethers. Using carbohydrates as nucleophiles, we synthesised a number of pseudodisaccharides.

  • 257.
    Frigell, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pearcey, J.A.
    Lowary, T.
    Cumpstey, Ian
    Carbasugar Analogues of Galactofuranose: Pseudodisaccharide Mimics of Fragments of Mycobacterial ArabinogalactanManuscript (preprint) (Other academic)
    Abstract [en]

    A partially protected carbasugar analogue of β-galactofuranose was converted into an α-galacto configured 1,2-epoxide, which was was opened by alcohols under Lewis acid catalysis with regioselective attack at C-1 to give β-galacto configured C-1 ethers. Using OH-5 and OH-6 carbagalactofuranose derivatives as nucleophiles, we synthesised pseudodisaccharide analogues of substructures of the arabinogalactan from M. tuberculosis. The dicarba analogue of the disaccharide Galf(β1→5)Galf was found to moderately inhibit the action of GlfT2 galactofuranosyl transferase from M. tuberculosis.

  • 258.
    Frigell, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pearcey, Jean A.
    Lowary, Todd L.
    Cumpstey, Ian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Carbasugar Analogues of Galactofuranosides: Pseudodisaccharide Mimics of Fragments of Mycobacterial Arabinogalactan2011In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 7, p. 1367-1375Article in journal (Refereed)
    Abstract [en]

    A partially protected carbasugar analogue of beta-galactofuranose was converted into an alpha-galacto-configured 1,2-epoxide, which was opened by alcohols under Lewis acid catalysis with regioselective attack at C-1 to give beta-galacto-configured C-1 ethers. Using OH-5 and OH-6 carbagalactofuranose derivatives as nucleophiles, we synthesised pseudodisaccharide analogues of substructures of the arabinogalactan from M. tuberculosis. The dicarba analogue of the disaccharide Galf(beta 1 -> 5) Galf was found to moderately inhibit the action of GlfT2 galactofuranosyl transferase from M. tuberculosis.

  • 259.
    Gao, Weiming
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Li, Mingrun
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Åkermark, Torbjörn
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Romare, Kristina
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sun, Licheng
    Royal Institute of Technology (KTH), Department of Organic Chemistry.
    Åkermark, Björn
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of a [3Fe2S] cluster with low redox potential from [2Fe2S] hydrogenase models: electrochemical and photochemical generation of hydrogen2011In: European Journal of Inorganic Chemistry, ISSN 1434-1948, E-ISSN 1099-1948, Vol. 2011, no 7, p. 1100-1105Article in journal (Refereed)
    Abstract [en]

    In the attempted replacement of carbon monoxide by the bis(phosphane) dppv in a dinuclear [2Fe2S] complex, a trinuclear [3Fe2S] complex with two bis(phosphane) ligands was unexpectedly obtained. On protonation, this gave a bridged hydride complex with an unusually low potential for the reduction of protons to molecular hydrogen. The redox potential also appears sufficiently positive for direct electron transfer from an excited [Ru(bpy)(3)](2+) sensitizer.

  • 260.
    Gao, Weiming
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Structural Chemistry.
    Åkermark, Torbjörn
    Li, Mingrun
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Structural Chemistry.
    Eriksson, Lars
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Structural Chemistry.
    Sun, Licheng
    Åkermark, Björn
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Attachment of a hydrogen-bonding carboxylate side chain to an [FeFe]-hydrogenase model complex: Influence on the catalytic mechanism2010In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 16, no 8, p. 2537-2546Article in journal (Refereed)
    Abstract [en]

    Azapropanedithiolate (adt)-bridged model complexes of [FeFe]-hydrogenase bearing a carboxylic acid functionality have been designed with the aim of decreasing the potential for reduction of protons to hydrogen. Protonation of the bisphosphine complexes 46 has been studied by in situ IR and NMR spectroscopy, which revealed that protonation with triflic acid most likely takes place first at the N-bridge for complex 4 but at the FeFe bond for complexes 5 and 6. Using an excess of acid, the diprotonated species could also be observed, but none of the protonated species was sufficiently stable to be isolated in a pure state. Electrochemical studies have provided an insight into the catalytic mechanisms under strongly acidic conditions, and have also shown that complexes 3 and 6 are electro-active in aqueous solution even in the absence of acid, presumably due to hydrogen bonding. Hydrogen evolution, driven by visible light, has been observed for three-component systems consisting of [Ru(bpy)3]2+, complex 1, 2, or 3, and ascorbic acid in CH3CN/D2O solution by on-line mass spectrometry.

  • 261.
    Gao, Yan
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Åkermark, Torbjörn
    Liu, Jianhui
    Sun, Licheng
    Åkermark, Björn
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Nucleophilic attack of hydroxide on a MnV oxo complex: a model of the O-O bond formation in the oxygen evolving complex of photosystem II2009In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 131, no 25, p. 8726-8727Article in journal (Refereed)
  • 262.
    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.

  • 263.
    Gemma, Emiliano
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lahmann, Martina
    Oscarson, Stefan
    Synthesis of the tetrasaccharide α-D-Glcp-(1→3)-α-D-Manp-(1→2)-α-D-Manp-(1→2)-α-D-Manp recognised by Calreticulin/Calnexin2005In: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 340, no 16, p. 2558-2562Article in journal (Refereed)
    Abstract [en]

    The title compound as its methyl glycoside was efficiently synthesized using a block synthesis approach. Halide-assisted glycosidations between 6-O-acetyl-2,3,4-tri-O-benzyl-α-d-glucopyranosyl iodide and ethyl 2-O-acetyl-4,6-di-O-benzyl-1-thio-α-d-mannopyranoside using triphenylphosphine oxide as promoter yielded, with complete α-selectivity, a disaccharide building block in high yield. The perbenzylated derivative of this proved to be an excellent donor affording 88% of the protected target tetrasaccharide in an NIS/AgOTf-promoted coupling to a known methyl dimannoside acceptor. Deprotection through catalytic hydrogenolysis then gave the target compound in 47% overall yield.

  • 264.
    Georgieva, Polina
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Quantum chemical modeling of enzymatic reactions: The Case of histone lysine methyltransferase2010In: Journal of Computational Chemistry, ISSN 0192-8651, E-ISSN 1096-987X, Vol. 31, no 8, p. 1707-1714Article in journal (Refereed)
    Abstract [en]

    Quantum chemical cluster models of enzyme active sites are today an important and powerful tool in the study of various aspects of enzymatic reactivity. This methodology has been applied to a wide spectrum of reactions and many important mechanistic problems have been solved. Herein, we report a systematic study of the reaction mechanism of the histone lysine methyltransferase (HKMT) SET7/9 enzyme, which catalyzes the methylation of the N-terminal histone tail of the chromatin structure. In this study, HKMT SET7/9 serves as a representative case to examine the modeling approach for the important class of methyl transfer enzymes. Active site models of different sizes are used to evaluate the methodology. In particular, the dependence of the calculated energies on the model size, the influence of the dielectric medium, and the particular choice of the dielectric constant are discussed. In addition, we examine the validity of some technical aspects, such as geometry optimization in solvent or with a large basis set, and the use of different density functional methods.

  • 265. Georgieva, Polina
    et al.
    Wu, Qian
    McLeish, Michael J.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    The reaction mechanism of phenylethanolamine N-methyltransferase: A density functional theory study2009In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1794, no 12, p. 1831-1837Article in journal (Refereed)
  • 266.
    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.

  • 267.
    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.

  • 268.
    Ghosh, Raju
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Stridfeldt, Elin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Metal-Free One-Pot Synthesis of Benzofurans2014In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 20, no 29, p. 8888-8892Article in journal (Refereed)
    Abstract [en]

    Ethyl acetohydroxamate was efficiently arylated with diaryliodonium salts at room temperature under transition-metal-free conditions. The obtained O-arylated products were reacted in situ with ketones under acidic conditions to yield substituted benzo[b]furans through oxime formation, [3,3]-rearrangement, and cyclization in a fast and operationally simple one-pot fashion without using excess reagents. Alternatively, the O-arylated products could be isolated or transformed in situ to aryloxyamines or O-arylaldoximes. The methodology was applied to the synthesis of Stemofuran A and the formal syntheses of Coumestan, Eupomatenoid 6, and (+)-machaeriol B.

  • 269.
    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.

  • 270.
    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.

  • 271.
    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.

  • 272.
    Gigant, Nicolas
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry. Université Paris-Sud, France.
    Quintin, Francois
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Preparation of Tetrasubstituted Olefins Using Mono or Double Aerobic Direct C-H Functionalization Strategies: Importance of Steric Effects2015In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 80, no 5, p. 2796-2803Article in journal (Refereed)
    Abstract [en]

    A novel protocol for the synthesis of tetrasubstituted olefins through a biomimetic approach has been explored. Both mono- and diarylations were performed under ambient oxygen pressure, giving a range of highly hindered tetrasubstituted alkenes. For diarylation of disubstituted substrates, it was demonstrated that the second arylation is the rate-limiting step of the overall transformation.

  • 273. Girgis, Adel S.
    et al.
    Mabied, Ahmed F.
    Stawinski, Jacek
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Hegazy, Lamees
    George, Riham F.
    Farag, Hanaa
    Shalaby, ElSayed M.
    Farag, I. S. Ahmed
    Synthesis and DFT studies of an antitumor active spiro-oxindole2015In: New Journal of Chemistry, ISSN 1144-0546, E-ISSN 1369-9261, Vol. 39, no 10, p. 8017-8027Article in journal (Refereed)
    Abstract [en]

    An anti-oncological active spiro-oxindole 7 was synthesized regioselectively via a [3+2]-cycloaddition reaction of azomethine ylide to exocyclic olefinic linkage of 4-piperidone 6, exhibiting properties against diverse tumor cell lines including leukemia, melanoma and cancers of the lung, colon, brain, ovary, breast, prostate, and kidney. Compound 7 crystallizes in the monoclinic system and P21/c space group with four molecules in the unit cell. The structure was also studied by AM1, PM3 and DFT techniques. DFT studies support the stereochemical selectivity of the reaction and determine the molecular electrostatic potential and frontier molecular orbitals.

  • 274. Godefroid, Marie
    et al.
    Svensson, Mona V
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cambier, Pierre
    Uzureau, Sophie
    Mirabella, Aurélie
    De Bolle, Xavier
    Van Cutsem, Pierre
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Letesson, Jean-Jacques
    Brucella melitensis 16M produces a mannan and other extracellular matrix components typical of a biofilm2010In: FEMS Immunology and Medical Microbiology, ISSN 0928-8244, E-ISSN 1574-695X, Vol. 59, no 3, p. 364-377Article in journal (Refereed)
  • 275.
    Goncalves, Sylvie
    et al.
    Universite de Strasbourg, Faculte de Pharmacie UMR/CNRS 7199, Laboratoire des Systemes Chimiques Fonctionnels, Illkirch, France.
    Santoro, Stefano
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Nicolas, Marc
    Les Laboratoires Pierre Fabre, Centre de Developpement Chimique et Industriel, Gaillac, France.
    Wagner, Alain
    Universite de Strasbourg, Faculte de Pharmacie UMR/CNRS 7199, Laboratoire des Systemes Chimiques Fonctionnels, Illkirch, France.
    Maillos, Philippe
    Les Laboratoires Pierre Fabre, Centre de Developpement Chimique et Industriel, Gaillac, France.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Baati, Rachid
    Universite de Strasbourg, Faculte de Pharmacie UMR/CNRS 7199, Laboratoire des Systemes Chimiques Fonctionnels, Illkirch, France.
    Cationic cyclization of 2-alkenyl-1,3-dithiolanes: DiastereoselectiveSynthesis of trans-decalins2011In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 76, no 9, p. 3274-3285Article in journal (Refereed)
    Abstract [en]

    An unprecedented and highly diastereoselective 6-endo-trig cyclization of 2-alkenyl-1,3-dithiolanes has beendeveloped yielding trans-decalins, an important scaffold present in numerous di- and triterpenes. The novelty of this 6-endo-trigc yclization stands in the stepwise mechanism involving 2-alkenyl-1,3-dithiolane, acting as a novel latent initiator. It is suggested that the thioketal opens temporarily under the influence of TMSOTf, triggering the cationic 6-endo-trig cyclization, andcloses after C−C bond formation and diastereoselective protonation to terminate the process. DFT calculations confirm this mechanistic proposal and provide a rationale for the observed diastereoselectivity. The reaction tolerates a wide range of functionalities and nucleophilic partners within the substrate. We have also shown that the one-pot 6-endo-trig cyclization followedby in situ 1,3-dithiolane deprotection afford directly the corresponding ketone. This improvement allowed the achievement of the shortest total synthesis of triptophenolide and the shortest formal synthesis of triptolide.

  • 276.
    González Miera, Greco
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Homogeneous and heterogeneous Cp*Ir(III) catalytic systems: Mechanistic studies of redox processes catalyzed by bifunctional iridium complexes, and synthesis of iridium-functionalized MOFs2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The purpose of this doctoral thesis is to investigate and develop catalytic processes mediated by iridium(III) complexes. By understanding the mechanisms, the weaknesses of the designed catalysts can be identified and be overcome in the following generation.

    The thesis is composed of two general sections dedicated to the synthesis and applications of homogeneous catalysts and to the preparation of heterogeneous catalysts based on metal-organic frameworks (MOFs). After a general introduction (Chapter 1), the first part of the thesis (Chapters 2-4, and Appendix 1) covers the use of several homogeneous bifunctional [Cp*Ir(III)] catalysts in a variety of chemical transformations, as well as mechanistic studies.

    Chapter 2 summarizes the studies on the N-alkylation of anilines with benzyl alcohols catalyzed by bifunctional Ir(III) complexes. Mechanistic investigations when the reactions were catalyzed by Ir(III) complexes with a hydroxy-functionalized N-heterocyclic carbene (NHC) ligand are discussed, followed by the design of a new generation of catalysts. The chapter finishes presenting the improved catalytic performance of these new complexes.   

    A family of these NHC-iridium complexes was evaluated in the acceptorless dehydrogenation of alcohols, as shown in Chapter 3. The beneficial effect of a co-solvent was investigated too. Under these base-free conditions, a wide scope of alcohols was efficiently dehydrogenated in excellent yields. The unexpected higher activity of the hydroxy-containing bifunctional NHC-Ir(III) catalysts, in comparison to that of the amino-functionalized one, was investigated experimentally.

    In the fourth chapter, the catalytic process presented in Chapter 3 was further explored on 1,4- and 1,5-diols, which were transformed into their corresponding tetrahydrofurans and dihydropyrans, respectively. Mechanistic investigations are also discussed.

    In the second part of the thesis (Chapter 5), a Cp*Ir(III) complex was immobilized into a MOF. The heterogenization of the metal complex was achieved efficiently, reaching high ratios of functionalization. However, a change in the topology of the MOF was observed. In this chapter, the use of advanced characterization techniques such as X-ray absorption spectroscopy (XAS) and pair distribution function (PDF) analyses enabled to study a phase transformation in these materials.

  • 277.
    González Miera, Greco
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Nonclassical cyclodehydration of diols assisted by metal-ligand cooperation2017Article in journal (Refereed)
  • 278.
    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.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    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.

  • 279.
    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) Complexes2018In: Organometallics, ISSN 0276-7333, E-ISSN 1520-6041, Vol. 37, no 5, p. 636-644Article 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.

  • 280. Goulart, Paula N.
    et al.
    da Silva, Clarissa O.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    The importance of orientation of exocyclic groups in a naphthoxyloside: A specific rotation calculation study2017In: Journal of Physical Organic Chemistry, ISSN 0894-3230, E-ISSN 1099-1395, Vol. 30, no 12, article id e3708Article in journal (Refereed)
    Abstract [en]

    2-Naphthyl -d-xylopyranoside (XylNap) inhibits -1,4-galactosyltransferase 7 (4GalT7) and thereby growth of tumor cells both in vitro and in vivo. The binding pocket of 4GalT7 has a defined orientation of hydrogen bond acceptors and hydrophobic moiety. Knowing the orientation of the hydroxyl and naphthyl groups of this molecule would help in the development of more efficient inhibitors. In this work, we have tried, for the first time, to determine the exocyclic hydroxyl and aglycon groups orientation of XylNap, using ab initio descriptions, and calculation of the specific rotation values, in methanol solutions, using 2 different solvent descriptions: a dielectric continuum approach (polarizable continuum model [PCM]) and a microsolvated+continuum approach (MS+PCM). In the PCM approach, [](D)=-59 deg/(dm(g/cm(3))) whereas for the MS+PCM approach [](D)=-29 deg/(dm(g/cm(3))). The latter is in excellent agreement with the experimentally determined value in methanol solution, viz, [](D)=-30 deg/(dm(g/cm(3))). This agreement allows us to say that the hydroxyl groups have similar orientations in xylose and XylNap, and the naphthyl group has a very well-defined dihedral angle value in the most abundant conformations.

  • 281.
    Gudmundsson, Arnar
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Gustafson, Karl P. J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Yang, Bin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Efficient Formation of 2,3-Dihydrofurans via Iron-Catalyzed Cycloisomerization of alpha-Allenols2018In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 8, no 1, p. 12-16Article in journal (Refereed)
    Abstract [en]

    Herein, we report a highly efficient iron-catalyzed intramolecular nucleophilic cyclization of alpha-allenols to furnish substituted 2,3-dihydrofurans under mild reaction conditions. A highly diastereoselective variant of the reaction was developed as well, giving diastereomeric ratios of up to 98:2. The combination of the iron-catalyzed cycloisomerization with enzymatic resolution afforded the 2,3-dihydrofuran in high ee. A detailed DFT study provides insight into the reaction mechanism and gives a rationalization for the high chemo-and diastereoselectivity.

  • 282. Gupta, Arvind Kumar
    et al.
    Akkarasamiyo, Sunisa
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Orthaber, Andreas
    Rich Coordination Chemistry of pi-Acceptor Dibenzoarsole Ligands2017In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 56, no 8, p. 4504-4511Article in journal (Refereed)
    Abstract [en]

    A series of dibenzoarsole (also known as 9-arsafluorene) derivatives have been prepared, and their coordination chemistry has been investigated. The different ligand topology and the arsenic substituents govern the reactivity of the ligands. We report various crystal structures of palladium and platinum complexes derived from this family of ligands. The biphenyl backbone of the bridged bidentate ligands allows very flexible coordination. We have also studied the application of an allylic Pd complex in nucleophilic substitution reactions, revealing that the benzoarsole substituent is susceptible to metal insertion.

  • 283.
    Gustafson, Karl P. J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Studies on Metalloenzymatic Dynamic Kinetic Resolutions and Iron-Catalyzed Reactions of Allenes2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main focus of this thesis lies in the development of new transition metal-catalyzed chemoenzymatic dynamic kinetic resolutions (DKR) of both alcohols and amines. The first part of the thesis deals with the development of new heterogeneous systems for the DKR of amines. The racemization catalysts in these different systems are all composed of palladium nanoparticles supported on either mesoporous silica or incorporated in a biocomposite that is composed of a bioactive cross-linked enzyme aggregate. 

    The second part of the thesis deals with the development of a homogeneous iron catalyst in the racemization of sec-alcohols for the implementation in a chemoenzymatic DKR. Two protocols for the racemization of sec-alcohols are reported. The first one could not be combined with a chemoenzymatic kinetic resolution, although this was overcome in the second iron based protocol. 

    Following the successful iron catalyzed chemoenzymatic DKR of sec-alcohols, the iron catalyst was used in the cyclization of α-allenic alcohols and N-protected amines to furnish 2,3-dihydrofurans and 2,3-dihydropyrroles, respectively. The cyclization is proceeding in a diastereoselective manner.

    The last part of the thesis deals with attempts to further elucidate the mechanism of activation of a known ruthenium racemization catalyst. X-ray absorption spectroscopy using synchrotron radiation was used for this purpose.

  • 284.
    Gustafson, Karl P. J.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Guðmundsson, Arnar
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bajnóczi, Éva
    Ning, Yuan
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Persson, Ingmar
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    In-Situ Structure Determination of a Ruthenium Racemization Catalyst and its Activated Intermediates using X-ray Absorption SpectroscopyManuscript (preprint) (Other academic)
  • 285.
    Gustafson, Karl P. J.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Görbe, Tamás
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    de Gonzalo Calvo, Gonzalo
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Yuan, Ning
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Schreiber, Cynthia
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Shchukarev, Andrey
    Tai, Cheuk-Wai
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Persson, Ingmar
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Application and further structure elucidation of Pd(0)-CalB CLEA biohybrid catalyst- Chemoenzymatic dynamic kinetic resolution of primary benzylic aminesManuscript (preprint) (Other academic)
  • 286.
    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.

  • 287.
    Guðmundsson, Arnar
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Gustafson, Karl P. J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Khanh Mai, Binh
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Hobiger, Viola
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Yang, Bin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Iron Catalyzed Cyclization of N-protected a-Allenic Amines to 2,3-dihydropyrrolesManuscript (preprint) (Other academic)
  • 288.
    Görbe, Tamás
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Heterogeneous catalysis in racemization and kinetic resolution along a journey in protein engineering2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The first part of my thesis concerns the use of heterogeneous acidic resins for racemization of tert-alcohols without any side-product formation. The focus was to develop a system which can be further extended to a DKR protocol consisting of an enzymatic KR reaction. Based on our knowledge of the resins, an unexpected migratory DKR protocol turned out to be an efficient method for the synthesis of carbocyclic allylic carbinols.

    The development of enzyme and metal catalyst hybrids was already an ongoing theme in our group. A supporter-free biohybrid catalyst was developed which can be used in several different types of reactions. The Pd(0)-CalB CLEA catalyst was applied in a two-step-cascade transformation and in the DKR of benzylic primary amines. The catalyst was characterized by different analytical techniques, to understand its composition and structure.

    The enzymes have always been the main focus of the studies and therefore wild type enzymes were initially utilized. However, these natural biocatalysts are associated with certain limitations. In contrast, protein engineering allows for enzymes to be modified and optimized. We have used the technique to create a subtilisin Carlsberg mutant, which was studied both by modeling and in vitro. The mutant was found to catalyze the (S)-selective transesterification of sec-alcohols containing long aliphatic carbon chains, and it also exhibited higher performance in organic solvent.

    The last project concerned the protein engineering of CalA enzyme towards tert-alcohols. The kinetic resolution of tert-alcohols with this enzyme is very slow but it occurs with good enantioselectivity. The aim was therefore to improve the activity of CalA via protein engineering. Seven amino acids were mutated close to the active site and a library was created based on our prediction. Throughout the screening, a few variants showed higher activity, which were sequenced and further analyzed in the transesterification of tert-alcohols.

  • 289.
    Görbe, Tamás
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Gustafson, Karl P. J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Verho, Oscar
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kervefors, Gabriella
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Zheng, Haoquan
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Zou, Xiaodong
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Johnston, Eric V.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Design of a Pd(0)-CalB CLEA Biohybrid Catalyst and Its Application in a One-Pot Cascade Reaction2017In: ACS Catalysis, ISSN 2155-5435, E-ISSN 2155-5435, Vol. 7, no 3, p. 1601-1605Article in journal (Refereed)
    Abstract [en]

    Herein, a design of a biohybrid catalyst is described, consisting of Pd nanoparticles and a cross-linked network of aggregated lipase B enzyme of Candida antarctica (CalB CLEA) functioning as an active support for the Pd nanoparticles. Both entities of the hybrid catalyst showed good catalytic activity. The applicability was demonstrated in a one-pot reaction, where the Pd-catalyzed cycloisomerization of 4-pentynoic acid afforded a lactone that serves as an acyl donor in a subsequent selective enzymatic kinetic resolution of a set of sec-alcohols. The catalyst proved to be robust and could be recycled five times without a significant loss of activity.

  • 290.
    Görbe, Tamás
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lihammar, Richard
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Heterogeneous Acid-Catalyzed Racemization of Tertiary Alcohols2018In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 24, no 1, p. 77-80Article in journal (Refereed)
    Abstract [en]

    Tertiary alcohols are important structural motifs in natural products and building blocks in organic synthesis but only few methods are known for their enantioselective preparation. Chiral resolution is one of these approaches that leaves one enantiomer (50% of the material) unaffected. An attractive method to increase the efficiency of those resolutions is to racemize the unaffected enantiomer. In the present work, we have developed a practical racemization protocol for tertiary alcohols. Five different acidic resin materials were tested. The Dowex 50WX8 was the resin of choice since it was capable of racemizing tertiary alcohols without any byproduct formation. Suitable solvents and a biphasic system were investigated, and the optimized system was capable of racemizing differently substituted tertiary alcohols.

  • 291.
    Görbe, Tamás
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Löfgren, Johanna
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Oschmann, Michael
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    S. Humble, Maria
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Transesterification of tert-Alcohols by Engineered Candida antarctica Lipase AManuscript (preprint) (Other academic)
  • 292.
    Hamark, Christoffer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    The sweet side of molecular structure: NMR spectroscopic studies of glycans and their interactions with proteins2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, within the topic of bioorganic chemistry, the molecular structure of carbohydrates has been studied. Carbohydrates, or glycans, are ubiquitous biomolecules exhibiting a wide range of biological roles. The specific functions of these molecules are largely determined by their interactions with proteins and molecular structure ultimately governs such specialized recognition events.

    Glycan-binding proteins, such as lectins or enzymes, often interact with their sweet ligands in a transient fashion and nuclear magnetic resonance spectroscopy (NMR) is a viable technique to probe these complexes. In particular, ligand-based NMR techniques have been employed, typically in combination with other biophysical as well as biochemical and computational methods. The aim of this work has been to gain new insights about specific biological systems, to develop methods and to devise protocols for their studies.

    The first two papers cover NMR-interaction studies of native ligands as well as inhibitor glycans with the enzyme hen egg-white lysozyme and the lectin botulinum neurotoxin type A. Screening experiments were performed to investigate ligand affinities and selectivities. Solution models in combination with X-ray crystal structures were compared in order to evaluate their agreement and the details of interactions.

    A method for application in carbohydrate ligand NMR-screening was developed in paper three. The heteronucleus selenium was exploited as a reporter of selenoglycosides binding to lectins. 77Se NMR spectroscopy proved sensitive to binding events and the presented approach should be useful in large screenings of glycomimetic inhibitors.  In order to obtain sufficient amounts of glycans for bioorganic studies their production often relies on chemical synthesis. In the last paper, the structure of some conformationally highly activated glycosyl donors was thoroughly investigated and related to their reactivity in synthetic glycosylation reactions.  

  • 293.
    Hamark, Christoffer
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Landström, Jens
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    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.
    Ethyl 3,6-di-O-benzyl-2-deoxy-N-phthalimido-1-thio-β-D-glucopyranoside2010In: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. E66, p. o3250-o3251Article in journal (Refereed)
    Abstract [en]

    In the title compound, C30H31NO6S, the plane of the N-phthalimido group is nearly orthogonal to the least-squares plane of the sugar ring (defined by atoms C2, C3, C5 and O5 using standard glucose nomenclature), making a dihedral angle of 72.8 (1)°. The thioethyl group has the exo-anomeric conformation. The hydroxy group forms an intermolecular hydrogen bond to the O atom in the sugar ring, generating [100] chains. There are four close - contacts with centroid-centroid distances less than 4.0 Å, all with dihedral angles between the interacting systems of only 8°, supporting energetically favourable stacking interactions

  • 294.
    Hamark, Christoffer
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Landström, Jens
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    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.
    Ethyl 4,6-O-benzylidene-2-deoxy-N-phthalimido-1-thio-β-D-glucopyranoside2010In: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. E66, p. o3249-Article in journal (Refereed)
  • 295.
    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.

  • 296. Hammarström, Lars G. J.
    et al.
    Harmel, Robert K.
    Granath, Mikael
    Ringom, Rune
    Gravenfors, Ylva
    Stockholm University, Faculty of Science, Department of Organic Chemistry. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Färnegårdh, Katarina
    Stockholm University, Faculty of Science, Department of Organic Chemistry. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Svensson, Per H.
    Wennman, David
    Lundin, Göran
    Roddis, Ylva
    Kitambi, Satish S.
    Bernlind, Alexandra
    Lehmann, Fredrik
    Ernfors, Patrik
    The Oncolytic Efficacy and in Vivo Pharmacokinetics of [2-(4-Chlorophenyl)quinolin-4-yl](piperidine-2-yl)methanol (Vacquinol-1) Are Governed by Distinct Stereochemical Features2016In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 59, no 18, p. 8577-8592Article in journal (Refereed)
    Abstract [en]

    Glioblastoma remains an incurable brain cancer. Drugs developed in the past 20 years have not improved the prognosis for patients, necessitating the development of new treatments. We have previously reported the therapeutic potential of the quinoline methanol Vacquinol-1 (1) that targets glioblastoma cells and induces cell death by catastrophic vacuolization. Compound 1 is a mixture of four stereoisomers due to the two adjacent stereogenic centers in the molecule, complicating further development in the preclinical setting. This work describes the isolation and characterization of the individual isomers of 1 and shows that these display stereospecific pharmacokinetic and pharmacodynamic features. In addition, we present a stereoselective synthesis of the active isomers, providing a basis for further development of this compound series into a novel experimental therapeutic for glioblastoma.

  • 297.
    Hansson, Jonas
    Stockholm University.
    Synthesis of phosphate-containing oligosaccharides corresponding to capsular antigen structures from Haemophilus influenzae2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes the synthesis of spacer-equipped di- and trimeric oligosaccharide structures corresponding to fragments of the capsular polysaccharides of Haemophilus influenzae types c and f. Both of these polysaccharides are of the teichoic acid type, built up by disaccharide repeating units linked via interglycosidic phosphodiester bonds. Introduction of the phosphodiester linkages was accomplished employing the glycosyl H-phosphonate method. The syntheses are designed in such a way as to allow the formation of even larger structures, as well as conjugation to a carrier protein. The first section of this thesis presents a general overview of the biological significance and structural features of anomeric phosphodiesters and synthetic approaches towards these structures, including a literature survey of research in this area during the past decade. In the second part, a new approach to the synthesis of anomeric phosphodiester linkages, utilizing non-anomeric glycosyl H-phosphonate acceptors and various galactosyl donors in glycosylation reactions, is described. Finally, synthesis of the capsular polysaccharide fragments of H. influenzae types c and f is discussed.

  • 298. 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.

  • 299. Hatcher, Elizabeth
    et al.
    Säwén, Elin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    MacKerell, Jr., Alexander D.
    Conformational properties of methyl β-maltoside and methyl α- and β-cellobioside disaccharides2011In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 115, no 3, p. 597-608Article in journal (Refereed)
    Abstract [en]

    An investigation of the conformational properties of methyl β-maltoside, methyl α-cellobioside, and methyl β-cellobioside disaccharides using NMR spectroscopy and molecular dynamics (MD) techniques, is presented. Emphasis is placed on validation of a recently presented force field for hexopyranose disaccharides followed by elucidation of the conformational properties of two different types of glycosidic linkages, α-(1 → 4) and β-(1 → 4). Both gas-phase and aqueous-phase simulations are performed to gain insight into the effect of solvent on the conformational properties. A number of transglycosidic J-coupling constants and proton−proton distances are calculated from the simulations and are used to identify the percent sampling of the three glycosidic conformations (syn, anti-, and anti-ψ) and, in turn, describe the flexibility around the glycosidic linkage. The results show the force field to be in overall good agreement with experiment, although some very small limitations are evident. Subsequently, a thorough hydrogen bonding analysis is performed to obtain insights into the conformational properties of the disaccharides. In methyl β-maltoside, competition between HO2′−O3 intramolecular hydrogen bonding and intermolecular hydrogen bonding of those groups with solvent leads to increased sampling of syn, anti-, and anti-ψ conformations and better agreement with NMR J-coupling constants. In methyl α- and β-cellobioside, O5′−HO6 and HO2′−O3 hydrogen bonding interactions are in competition with intermolecular hydrogen bonding involving the solvent molecules. This competition leads to retention of the O5′−HO3 hydrogen bond and increased sampling of the syn region of the /ψ map. Moreover, glycosidic torsions are correlated to the intramolecular hydrogen bonding occurring in the molecules. The present results verify that in the β-(1 → 4)-linkage intramolecular hydrogen bonding in the aqueous phase is due to the decreased ability of water to successfully compete for the O5′ and HO3 hydrogen bonding moieties, in contrast to that occurring between the O5′ and HO6 atoms in this α-(1 → 4)-linkage.

  • 300. Hayashi, Yukiko
    et al.
    Santoro, Stefano
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Azuma, Yuki
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ohshima, Takashi
    Mashima, Kazushi
    Enzyme-Like Catalysis via Ternary Complex Mechanism: Alkoxy-Bridged Dinuclear Cobalt Complex Mediates Chemoselective O-Esterification over N-Amidation2013In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 135, no 16, p. 6192-6199Article in journal (Refereed)
    Abstract [en]

    Hydroxy group-selective acylation in the presence of more nucleophilic amines was achieved using acetates of first-row late transition metals, such as Mn, Fe, Co, Cu, and Zn. Among them, cobalt(II) acetate was the best catalyst in terms of reactivity and selectivity. The combination of an octanuclear cobalt carboxylate cluster [Co-4(OCOR)(6)O](2) (2a: R = CF3, 2b: R = CH3, 2c: R = Bu-t) with nitrogen-containing ligands, such as 2,2'-bipyridine, provided an efficient catalytic system for transesterification, in which an alkoxide-bridged dinuclear complex, Co-2((OCOBu)-Bu-t)(2)-(bpy)(2)(mu(2)-OCH2-C6H4-4-CH3)(2) (10), was successfully isolated as a key intermediate. Kinetic studies and density functional theory calculations revealed Michaelis-Menten behavior of the complex 10 through an ordered ternary complex mechanism similar to dinuclear metallo-enzymes, suggesting the formation of alkoxides followed by coordination of the ester.

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