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  • 1. Chojnacka, Kinga
    et al.
    Santoro, Stefano
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Awartani, Radi
    Richards, Nigel G. J.
    Himo, Fahmi
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Aponick, Aaron
    Synthetic studies on the solanacol ABC ring system by cation-initiated cascade cyclization: implications for strigolactone biosynthesis2011Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, nr 15, s. 5350-5353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We report a new method for constructing the ABC ringsystem of strigolactones, in a single step from a simple linearprecursor by acid-catalyzed double cyclization. The reactionproceeds with a high degree of stereochemical control, whichcan be qualitatively rationalized usingDFT calculations. Ourconcise synthetic approach offers a new model for thinkingabout the (as yet) unknown chemistry that is employed in thebiosynthetic pathways leading to this class of plant hormones.

  • 2. Daikoku, S.
    et al.
    Pendrill, Robert
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Kanie, Y.
    Ito, Y.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Kanie, O.
    Synthesis and structural investigation of a series of mannose-containing oligosaccharides using mass spectrometry2018Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 16, nr 2, s. 228-238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A series of compounds associated with naturally occurring and biologically relevant glycans consisting of alpha-mannosides were prepared and analyzed using collision-induced dissociation (CID), energy-resolved mass spectrometry (ERMS), and H-1 nuclear magnetic resonance spectroscopy. The CID experiments of sodiated species of disaccharides and ERMS experiments revealed that the order of stability of mannosyl linkages was as follows: 6-linked > 4-linked >= 2-linked > 3-linked mannosyl residues. Analysis of linear trisaccharides revealed that the order observed in disaccharides could be applied to higher glycans. A branched trisaccharide showed a distinct dissociation pattern with two constituting disaccharide ions. The estimation of the content of this ion mixture was possible using the disaccharide spectra. The hydrolysis of mannose linkages at 3- and 6-positions in the branched trisaccharide revealed that the 3-linkage was cleaved twice as fast as the 6-linkage. It was observed that the solution-phase hydrolysis and gas-phase dissociation have similar energetics.

  • 3.
    Deska, Jan
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Bäckvall, Jan-Erling
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Enzymatic kinetic resolution of primary allenic alcohols. Application to the total synthesis and stereochemical assignment of striatisporolide A2009Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 7, nr 17, s. 3379-3381Artikel i tidskrift (Refereegranskat)
  • 4.
    Dziedzic, Pawel
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Weibiao, Zou
    Hafrén, Jonas
    Córdova, Armando
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    The small peptide-catalyzed direct asymmetric aldol reaction in water2006Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 4, s. 38-40Artikel i tidskrift (Refereegranskat)
  • 5.
    Engelmark Cassimjee, Karim
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Manta, Bianca
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Himo, Fahmi
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    A quantum chemical study of the ω-transaminase reaction mechanism2015Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, nr 31, s. 8453-8464Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ω-Transaminases are valuable tools in biocatalysis due to their stereospecificity and their broad substrate range. In the present study, the reaction mechanism of Chromobacterium violaceum ω-transaminase is investigated by means of density functional theory calculations. A large active site model is designed based on the recent X-ray crystal structure. The detailed energy profile for the half-transamination of (S)-1-phenylethylamine to acetophenone is calculated and the involved transition states and intermediates are characterized. The model suggests that the amino substrate forms an external aldimine with the coenzyme pyridoxal-5′-phosphate (PLP), through geminal diamine intermediates. The external aldimine is then deprotonated in the rate-determining step, forming a planar quinonoid intermediate. A ketimine is then formed, after which a hemiaminal is produced by the addition of water. Subsequently, the ketone product is obtained together with pyridoxamine-5′-phosphate (PMP). In the studied half-transamination reaction the ketone product is kinetically favored. The mechanism presented here will be valuable to enhance rational and semi-rational design of engineered enzyme variants in the development of ω-transaminase chemistry.

  • 6.
    Engström, Karin
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Vallin, Michaela
    Syrén, Per-Olof
    Hult, Karl
    Bäckvall, Jan-E.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Mutated variant of Candida antarctica lipase B in (S)-selective dynamickinetic resolution of secondary alcohols2011Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, nr 1, s. 81-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An (S)-selective dynamic kinetic resolution of secondaryalcohols, employing a mutated variant of Candida antarcticalipase B (CalB) gave products in 84–88% yield and in 90–97%ee.

  • 7.
    Engström, Olof
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Muñoz, Antonio
    Illescas, Beatriz M.
    Martin, Nazario
    Ribeiro-Viana, Renato
    Rojo, Javier
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Investigation of glycofullerene dynamics by NMR spectroscopy2015Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, nr 32, s. 8750-8755Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glycofullerenes, in which carbohydrate molecules are attached via a linker to a [60]fullerene core, facilitate spherical presentation of glyco-based epitopes. We herein investigate the dynamics of two glycofullerenes, having 12 and 36 mannose residues at their periphery, by NMR translational diffusion and quantitative C-13 relaxation studies employing a model-free approach for their interpretation. The sugar residues are shown to be highly flexible entities with S-2 < 0.2 in both compounds. Notably, the larger glycofullerene with longer linkers shows faster internal dynamics and higher flexibility than its smaller counterpart. The dynamics and flexibility as well as the slower translational diffusion of the larger glycofullerene, thereby favoring rebinding to a receptor, may together with its spatial extension explain why it is better than the smaller one at blocking the DC-SIGN receptor and inhibiting the infection by pseudotyped Ebola virus particles.

  • 8.
    Jonsson, K. Hanna M.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Säwén, Elin
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Studies on the conformational flexibility of alpha-L-rhamnose-containing oligosaccharides using C-13-site-specific labeling, NMR spectroscopy and molecular simulations: implications for the three-dimensional structure of bacterial rhamnan polysaccharides2012Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 10, nr 12, s. 2453-2463Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bacterial polysaccharides are comprised of a variety of monosaccharides, L-rhamnose (6-deoxy-L-mannose) being one of them. This sugar is often part of alpha-(1 -> 2)- and/or alpha-(1 -> 3)-linkages and we have therefore studied the disaccharide alpha-L-Rhap-(1 -> 2)-alpha-L-Rhap-OMe to obtain information on conformational preferences at this glycosidic linkage. The target disaccharide was synthesized with C-13 site-specific labeling at C1' and at C2', i.e., in the terminal group. 2D H-1, C-13-HSQC-HECADE and H-1, C-13-J-HMBC NMR experiments, 1D C-13 and H-1 NMR spectra together with total line-shape analysis were used to extract conformationally dependent hetero- and homonuclear spin-spin coupling constants. This resulted in the determination of (2)JC(2',H1'), (3)J(C1',C1), (3)J(C1',C3), (3)J(C2',C2), (2)J(C1',C2), (1)JC(1',C2'), and (1)J(C1',H1'). These data together with previously determined J(CH) and H-1, H-1 NOEs result in fourteen conformationally dependent NMR parameters that are available for analysis of glycosidic linkage flexibility and conformational preferences. A 100 ns molecular dynamics (MD) simulation of the disaccharide with explicit water molecules as solvent showed a major conformational state at phi(H) approximate to 40 degrees and psi(H) approximate to -35 degrees, consistent with experimental NMR data. In addition, MD simulations were carried out also for alpha-L-Rhap-(1 -> 3)-alpha-L-Rhap-OMe and a rhamnan hexasaccharide. The gathered information on the oligosaccharides was used to address conformational preferences for a larger structure, a 2- and 3-linked nonasaccharide, with implications for the 3D structure of rhamnan polysaccharides, which should be regarded as flexible polymers.

  • 9.
    Kamerlin, Shina C. L.
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Wilkie, John
    The effect of leaving group on mechanistic preference in phosphate monoesterhydrolysis2011Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 9, nr 15, s. 5394-5406Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We present 2-dimensional potential energy surfaces and  transition states (TS) for water attack on a series of substituted phosphate monoester monoanions at the DFT level of theory, comparing a standard 6-31++g(d,p) basis set with a larger triple-zeta (augmented cc-pVTZ) basis set. Small fluorinated model compounds are used to simulate increasing leaving group stability without adding further geometrical complexity to the system. We demonstrate that whilst changing the leaving group causes little qualitative change in the potential energy surfaces (with the exception of the system with the most electron withdrawing leaving group, CF3O-, in which the associative pathway changes from a stepwise AN + DN pathway to a concerted ANDN pathway), there is a quantitative change in relative gas-phase and solution barriers for the two competing pathways. In line with previous studies, in the case of OCH3, the barriers for the associative and dissociative pathways are similar in solution, and the two pathways are equally viable and indistinguishable in solution. However, significantly increasing the stability of the leaving group (decreasing proton affinity, PA) results in the progressive favouring of a stepwise dissociative, DN + AN, mechanism over associative mechanisms.

  • 10.
    Landström, Jens
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Bergström, Maria
    Hamark, Christoffer
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Ohlson, Sten
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies2012Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 10, nr 15, s. 3019-3032Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    By examining the interactions between the protein hen egg-white lysozyme (HEWL) and commercially available and chemically synthesized carbohydrate ligands using a combination of weak affinity chromatography (WAC), NMR spectroscopy and molecular simulations, we report on new affinity data as well as a detailed binding model for the HEWL protein. The equilibrium dissociation constants of the ligands were obtained by WAC but also by NMR spectroscopy, which agreed well. The structures of two HEWL-disaccharide complexes in solution were deduced by NMR spectroscopy using H-1 saturation transfer difference (STD) effects and transferred H-1,H-1-NOESY experiments, relaxation-matrix calculations, molecular docking and molecular dynamics simulations. In solution the two disaccharides beta-D-Galp-(1 -> 4)-beta-D-GlcpNAc-OMe and beta-D-GlcpNAc-(1 -> 4)-beta-D-GlcpNAc-OMe bind to the B and C sites of HEWL in a syn-conformation at the glycosidic linkage between the two sugar residues. Intermolecular hydrogen bonding and CH/pi-interactions form the basis of the protein-ligand complexes in a way characteristic of carbohydrate-protein interactions. Molecular dynamics simulations with explicit water molecules of both the apo-form of the protein and a ligand-protein complex showed structural change compared to a crystal structure of the protein. The flexibility of HEWL as indicated by a residue-based root-mean-square deviation analysis indicated similarities overall, with some residue specific differences, inter alia, for Arg61 that is situated prior to a flexible loop. The Arg61 flexibility was notably larger in the ligand-complexed form of HEWL. N,N'-Diacetylchitobiose has previously been observed to bind to HEWL at the B and C sites in water solution based on H-1 NMR chemical shift changes in the protein whereas the disaccharide binds at either the B and C sites or the C and D sites in different crystal complexes. The present study thus highlights that protein-ligand complexes may vary notably between the solution and solid states, underscoring the importance of targeting the pertinent binding site(s) for inhibition of protein activity and the advantages of combining different techniques in a screening process.

  • 11. Llona-Minguez, Sabin
    et al.
    Throup, Adam
    Steiner, Emilie
    Lightowler, Molly
    Van der Haegen, Sandra
    Homan, Evert
    Eriksson, Lars
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för material- och miljökemi (MMK).
    Stenmark, Pål
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Jenmalm-Jensen, Annika
    Helleday, Thomas
    Novel spirocyclic systems via multicomponent aza-Diels-Alder reaction2017Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 15, nr 37, s. 7758-7764Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here we present a two-step diastereoselective methodology building on a multicomponent aza-Diels-Alder reaction. Using previously unexplored cyclic ketones, heterocyclic amines and cyclopentadiene derivatives, we obtained novel spiro-heterocyclic frameworks at the interphase between drug-like molecules and natural products.

  • 12.
    Olsson, Johan D M
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Landström, Jens
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Rönnols, Jerk
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Oscarson, Stefan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Synthesis of and molecular dynamics simulations on a tetrasaccharide corresponding to the repeating unit of the capsular polysaccharide from Salmonella enteritidis2009Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 7, nr 8, s. 1612-1618Artikel i tidskrift (Refereegranskat)
  • 13.
    Rönnols, Jerk
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Manner, Sophie
    Ellervik, Ulf
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Conformational effects due to stereochemistry and C3-substituents in xylopyranoside derivatives as studied by NMR spectroscopy2014Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 12, nr 40, s. 8031-8035Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Glycosaminoglycans contain a beta-D-xylopyranose residue at its reducing end, which links the polysaccharide to the protein in proteoglycans. 2-Naphthyl beta-D-xylopyranosides have shown inhibition of tumor growth and we herein investigate conformation and dynamics of compounds structurally and stereochemically modified at the C3 position as well as the influence of solvent. The 3-deoxygenated compound, the 3-C-methyl-substituted beta-D-xylopyranoside, beta-D-ribopyranoside, the 3-C-methyl-substituted beta-D-ribopyranoside as well as 2-naphthyl beta-D-xylopyranoside were analyzed by NMR spectroscopy. Conformational equilibria were dependent on the solvent of choice, either methanol-d(4) or chloroform-d, with mainly C-4(1) and C-1(4) conformations present but also skew conformations to some extent. Intramolecular hydrogen bonding was concluded to be important for the 3-C-methyl-substituted beta-D-xylopyranosides in the non-polar solvent. Dynamic NMR (DNMR) spectroscopy was carried out for the 3-deoxygenated compound, which at 25 degrees C in methanol-d(4) exists with equally populated states of the C-4(1) and the C-1(4) conformations, but at -100 degrees C only a few percent is present of the latter. Using C-13 NMR detection for DNMR, resonance lines were shown to broaden at -40 degrees C and to sharpen again below -90 degrees C, without the emergence of a second set of NMR resonances, a typical behavior for an unequally populated equilibrium. The enthalpy and entropy activation barriers were calculated and resulted in Delta H-double dagger = 47.3 kJ mol(-1) and Delta S-double dagger = 54 J mol(-1) K-1.

  • 14.
    Rönnols, Jerk
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Manner, Sophie
    Siegbahn, Anna
    Ellervik, Ulf
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Exploration of conformational flexibility and hydrogen bonding of xylosides in different solvents, as a model system for enzyme active site interactions2013Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 11, nr 33, s. 5465-5472Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The predominantly populated conformation of carbohydrates in solution does not necessarily represent the biologically active species; rather, any conformer accessible without too large an energy penalty may be present in a biological pathway. Thus, the conformational preferences of a naphthyl xyloside, which initiates in vivo synthesis of antiproliferative glycosaminoglycans, have been studied by using NMR spectroscopy in a variety of solvents. Equilibria comprising the conformations 4C12SO and 1C4 were found, with a strong dependence on the hydrogen bonding ability of the solvent. Studies of fluorinated analogues revealed a direct hydrogen bond from the hydroxyl group at C2 to the fluorine atom at C4 by a 1hJF4,HO2 coupling. Hydrogen bond directionality was further established via comparisons of fluorinated levoglucosan molecules.

  • 15.
    Rönnols, Jerk
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Walvoort, Marthe T. C.
    van der Marel, Gijsbert A.
    Codee, Jeroen D. C.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Chair interconversion and reactivity of mannuronic acid esters2013Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 11, nr 46, s. 8127-8134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Mannopyranosyluronic acids display a very unusual conformation behavior in that they often prefer to adopt a C-1(4) chair conformation. They are endowed with a strikingly high reactivity when used in a glycosylation reaction as a glycosyl donor. To investigate the unusual conformational behavior a series of mannuronic acid ester derivatives, comprising anomeric triflate species and O-methyl glycosides, was examined by dynamic NMR experiments, through lineshape analysis of H-1 and F-19 NMR spectra at various temperatures from -80 degrees C to 0 degrees C. Exchange rates between C-4(1) and C-1(4) chair conformations were found to depend on the electronic properties and the size of the C2 substituent (F, N-3 or OBn) and the aglycon, with higher exchange rates for the glycosyl triflates and smaller C2 substituents. Low temperature F-19 exchange spectroscopy experiments showed that the covalently bound anomeric triflates did not exchange with free triflate species present in the reaction mixture. To relate the conformational behavior of the intermediate triflates to their reactivity in a glycosylation reaction, their relative reactivity was determined via competition reactions monitored by H-1 NMR spectroscopy at low temperature. The 2-O-benzyl ether compound was found to be most reactive whereas the 2-fluoro compound - the most flexible of the studied compounds - was least reactive. Whereas the ring-flip of the mannuronic acids is important for the enhanced reactivity of the donors, the rate of the ring-flip has little influence on the relative reactivity.

  • 16. Siegbahn, Anna
    et al.
    Thorsheim, Karin
    Ståhle, Jonas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Manner, Sophie
    Hamark, Christoffer
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Persson, Andrea
    Tykesson, Emil
    Mani, Katrin
    Westergren-Thorsson, Gunilla
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Ellervik, Ulf
    Exploration of the active site of beta 4GalT7: modifications of the aglycon of aromatic xylosides2015Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 13, nr 11, s. 3351-3362Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Proteoglycans (PGs) are macromolecules that consist of long linear polysaccharides, glycosaminoglycan (GAG) chains, covalently attached to a core protein by the carbohydrate xylose. The biosynthesis of GAG chains is initiated by xylosylation of the core protein followed by galactosylation by the galactosyltransferase beta 4GalT7. Some beta-D-xylosides, such as 2-naphthyl beta-D-xylopyranoside, can induce GAG synthesis by serving as acceptor substrates for beta 4GalT7 and by that also compete with the GAG synthesis on core proteins. Here we present structure-activity relationships for beta 4GalT7 and xylosides with modifications of the aromatic aglycon, using enzymatic assays, cell studies, and molecular docking simulations. The results show that the aglycons reside on the outside of the active site of the enzyme and that quite bulky aglycons are accepted. By separating the aromatic aglycon from the xylose moiety by linkers, a trend towards increased galactosylation with increased linker length is observed. The galactosylation is influenced by the identity and position of substituents in the aromatic framework, and generally, only xylosides with beta-glycosidic linkages function as good substrates for beta 4GalT7. We also show that the galactosylation ability of a xyloside is increased by replacing the anomeric oxygen with sulfur, but decreased by replacing it with carbon. Finally, we propose that reaction kinetics of galactosylation by beta 4GalT7 is dependent on subtle differences in orientation of the xylose moiety.

  • 17.
    Slättegård, Rikard
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Teodorović, Peter
    Hadgu Kinfe, Henok
    Ravenscroft, Neil
    Gammon, David W.
    Oscarson, Stefan
    Synthesis of Structures Corresponding to the Capsular Polysaccharide of Neisseria meningitidis Group A2005Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 3, nr 20Artikel i tidskrift (Refereegranskat)
    Abstract [en]

     

     

     

     

    Four differently substituted trimers of the CPS repeating unit have been synthesised in order to investigate the

    dependence on oligosaccharide size, acetylation and mode of phosphorylation of glycoconjugate vaccines against

    Neisseria meningitidis

     

    group A. A spacer-containing starting monomer, a H-phosphonate elongating monomer and a

    6-

     

    O

    -phosphorylated H-phosphonate cap monomer have been synthesised and coupled together to afford, after

    deprotection, the target trimer structures differing in their acetylation and phosphorylation substitution

    pattern.

  • 18. Stamatov, Stephan D.
    et al.
    Stawinski, Jacek
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    O-Silylated C3-halohydrins as a novel class of protected building blocks for total, regio- and stereocontrolled synthesis of glycerolipid frameworks2010Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 8, nr 2, s. 463-477Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    We propose O-silylated C3-halohydrins [1(3)-O-silyl-2-O-acyl-, 1,2(2,3)-O-bis(silyl)-, and 1(3)-O-acyl-2-O-silyl-3(1)-halo-sn-glycerides] as new chirons in the total synthesis of glycerolipid constructs. These are efficiently producible via opening of the oxirane ring of the corresponding glycidyl derivatives and permit (i) displacement of the iodine by a requisite carboxylate in the presence of O-triisopropylsilyl (O-TIPS), O-tert-butyldimethylsilyl (O-TBDMS), and O-acyl substituents; (ii) selective acylation across an appropriate silyloxy system [e. g., O-TBDMS or O-triethylsilyl (O-TES)] of monoesterified haloglycerides; (iii) direct exchange of an O-silyl protection (e. g., O-TBDMS or O-TIPS) for a trichloroacetyl group; (iv) conversion of a terminal TBDMS group into the corresponding trifluoroacetate without affecting O-TIPS-, O-acyl- and iodo functions. The above transformations secure flexible routes to a variety of otherwise difficult-to-access key-intermediates [e.g., 1,2(2,3)-O-bis(acyl)-3(1)-trichloroacetyl-, 1,3-O-bis(acyl)-2-trichloroacetyl-, 1,2(2,3)-O-bis(acyl)-3(1)-O-TBDMS/TIPS-, 1,3-O-bis(acyl)-2-O-TIPS/TBDMS-, 1(3)-O-acyl-2-O-TIPS-, 1,2(2,3)-O-bis(acyl)-3(1)-iodo-sn-glycerols, etc.] and lend themselves to a powerful methodology for the preparation of di- and triacylglycerols as well as glycerol-based cationic lipids. The reactions involved are entirely regio- and stereospecific, avoid acyl migration, and can provide target compounds with a chosen absolute configuration from a single synthetic precursor.

  • 19.
    Säwén, Elin
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Hinterholzinger, Florian
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Landersjö, Clas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Conformational flexibility of the pentasaccharide LNF-2 deduced from NMR spectroscopy and molecular dynamics simulations2012Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 10, nr 23, s. 4577-4585Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Human milk oligosaccharides (HMOs) are important as prebiotics since they stimulate the growth of beneficial bacteria in the intestine and act as receptor analogues that can inhibit the binding of pathogens. The conformation and dynamics of the HMO Lacto-N-fucopentaose 2 (LNF-2), alpha-L-Fucp-(1 -> 4)-[beta-D-Galp-(1 -> 3)]-beta-D-GlcpNAc-(1 -> 3)-beta-D-Galp-(1 -> 4)-D-Glcp, having a Lewis A epitope, has been investigated employing NMR spectroscopy and molecular dynamics (MD) computer simulations. 1D H-1, H-1-NOESY experiments were used to obtain proton-proton cross-relaxation rates from which effective distances were deduced and 2D J-HMBC and 1D long-range experiments were utilized to measure trans-glycosidic (3)J(CH) coupling constants. The MD simulations using the PARM22/SU01 force field for carbohydrates were carried out for 600 ns with explicit water as solvent which resulted in excellent sampling for flexible glycosidic torsion angles. In addition, in vacuo MD simulations were performed using an MM3-2000 force field, but the agreement was less satisfactory based on an analysis of heteronuclear trans-glycosidic coupling constants. LNF-2 has a conformationally well-defined region consisting of the terminal branched part of the pentasaccharide, i.e., the Lewis A epitope, and a flexible beta-D-GlcpNAc-(1 -> 3)-beta-D-Galp-linkage towards the lactose unit, which is situated at the reducing end. For this beta-(1 -> 3)-linkage a negative. torsion angle is favored, when experimental NMR data is combined with the MD simulation in the analysis. In addition, flexibility on a similar time scale, i.e., on the order of the global overall molecular reorientation, may also be present for the. torsion angle of the beta-D-Galp-(1 -> 4)-D-Glcp-linkage as suggested by the simulation. It was further observed from a temperature variation study that some H-1 NMR chemical shifts of LNF-2 were highly sensitive and this study indicates that Delta delta/Delta T may be an additional tool for revealing conformational dynamics of oligosaccharides.

  • 20.
    Säwén, Elin
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Massad, Tariq
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för biokemi och biofysik.
    Landersjö, Clas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Damberg, Peter
    Widmalm, Göran
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Population distribution of flexible molecules from maximum entropy analysisusing different priors as background information: application to the phi,psi-conformational space of the a-(1→2)-linked mannose disaccharide presentin N- and O-linked glycoproteins2010Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 8, nr 16, s. 3684-3695Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The conformational space available to the flexible molecule a-D-Manp-(1→2)-a-D-Manp-OMe, amodel for the a-(1→2)-linked mannose disaccharide in N- or O-linked glycoproteins, is determinedusing experimental data and molecular simulation combined with a maximum entropy approach thatleads to a converged population distribution utilizing different input information. A database survey ofthe Protein Data Bank where structures having the constituent disaccharide were retrieved resulted inan ensemble with >200 structures. Subsequent filtering removed erroneous structures and gave thedatabase (DB) ensemble having three classes of mannose-containing compounds, viz., N- and O-linkedstructures, and ligands to proteins. A molecular dynamics (MD) simulation of the disaccharide revealeda two-state equilibrium with a major and a minor conformational state, i.e., the MD ensemble. Thesetwo different conformation ensembles of the disaccharide were compared to measured experimentalspectroscopic data for the molecule in water solution. However, neither of the two populations werecompatible with experimental data from optical rotation, NMR 1H,1H cross-relaxation rates as well ashomo- and heteronuclear 3J couplings. The conformational distributions were subsequently used asbackground information to generate priors that were used in a maximum entropy analysis. Theresulting posteriors, i.e., the population distributions after the application of the maximum entropyanalysis, still showed notable deviations that were not anticipated based on the prior information.Therefore, reparameterization of homo- and heteronuclear Karplus relationships for the glycosidictorsion angles f and y were carried out in which the importance of electronegative substituents on thecoupling pathway was deemed essential resulting in four derived equations, two 3JCOCC and two 3JCOCHbeing different for the f and y torsions, respectively. These Karplus relationships are denotedJCX/SU09. Reapplication of the maximum entropy analysis gave excellent agreement between theMD- and DB-posteriors. The information entropies show that the current reparametrization of theKarplus relationships constitutes a significant improvement. The fH torsion angle of the disaccharide isgoverned by the exo-anomeric effect and for the dominating conformation fH = -40◦ and yH = 33◦.The minor conformational state has a negative yH torsion angle; the relative populations of the majorand the minor states are ~3 : 1. It is anticipated that application of the methodology will be useful toflexible molecules ranging from small organic molecules to large biomolecules.

  • 21.
    Tinnis, Fredrik
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Adolfsson, Hans
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Asymmetric transfer hydrogenation of ketones catalyzed by rhodium complexes containing amino acid triazole ligands2010Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 8, nr 20, s. 4536-4539Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Active and selective catalysts for the asymmetric reduction of ketones, under transfer hydrogenation conditions, were obtained by combining [RhCl2Cp*](2), with a series of L-amino acid thioamide ligands functionalized with 1,2,3-triazoles. The obtained secondary alcohol products were formed with up to 93% ee.

  • 22.
    Yang, Hai-Bin
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    Selander, Nicklas
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för organisk kemi.
    A redox-economical synthesis of trifluoromethylated enamides with the Langlois reagent2017Ingår i: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 15, nr 8, s. 1771-1775Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A redox-economical strategy for the synthesis of trifluoromethylated enamides using copper catalysis is reported. The reaction employs the inexpensive Langlois reagent (CF3SO2Na) and takes place without the need of an external oxidant. The trifluoromethylated enamide products can easily be converted into the corresponding ketone, saturated amide or oxazole.

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