Change search
Refine search result
12 1 - 50 of 68
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1.
    Ahlsten, Nanna
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Transition metal-catalysed isomerisation of allylic alcohols: Applications to C−C, C−F and C−Cl bond formation2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The focus of this thesis has been to develop selective and atom-economical methods for carbon-carbon and carbon-heteroatom bond formation, and to some extent improve on existing findings in this area. More specifically, methods for the catalytic generation of enolates from allylic alcohols and their in situ functionalisation with electrophilic reagents are described.  

    In the first part of this thesis, a method for the Rh-catalysed redox-isomerisation of allylic alcohols into carbonyl compounds under environmentally benign conditions is described. The reaction takes place at room temperature, in the absence of acids or bases, using water as the only solvent, and it is applicable to both primary and secondary allylic alcohols.

    The second part describes the combination of an isomerisation reaction of allylic alcohols with a C−C bond formation, catalysed by a rhodium complex. In this way, allylic alcohols were coupled with aldehydes and N-tosylimines to give aldol and Mannich-type products. In addition to allylic alcohols, homoallylic and bishomoallylic alcohols could be used as enolate precursors, and this is the first report where the latter two substrate types have been used in such a reaction.       

    In the remaining parts of the thesis, an iridium-catalysed isomerisation of allylic alcohols has been combined with an electrophilic halogenation step to provide a conceptually new method for the synthesis of α-halogenated carbonyl compounds. In this way, α-fluoro and α-chloroketones have been synthesised as single constitutional isomers, with the regiochemistry of the final products determined by the position of the double bond in the allylic alcohols. The reactions are tolerant to air, run in water-organic solvent mixtures, and proceed at room temperature.

  • 2.
    Alam, Rauful
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mihai, Raducan
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Eriksson, Lars
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Szabo, Kalman J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Selective Formation of Adjacent Stereocenters by Allylboration of Ketones under Mild Neutral Conditions2013In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 15, no 10, p. 2546-2549Article in journal (Refereed)
    Abstract [en]

    Allylboronic acids readily react with a broad variety of ketones, affording homoallylic alcohols with adjacent quaternary and tertiary stereocenters. The reaction proceeds with very high anti stereoselectivity even if the substituents of the keto group have a similar size. a-Keto acids react with syn stereoselectivity probably due to the formation of acyl boronate intermediates. The allylation reactions proceed without added acids/bases under mild conditions. Because of this, many functionalities are tolerated even with in situ generated allylboronic acids.

  • 3.
    Alam, Rauful
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Raducan, Mihai
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Eriksson, Lars
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Szabó, Kálmán J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Diastereoselective allylboration of wide variety of carbonyl compounds using allylboronic acids: Construction of adjacent tertiary and quaternary centers2013In: Abstracts of papers of The American Chemical Society, American Chemical Society (ACS), 2013, Vol. 246, p. 364-ORGN-Conference paper (Refereed)
  • 4.
    Alamsetti, Santosh Kumar
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Persson, Andreas K. A.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Jiang, Tuo
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Scalable Synthesis of Oxazolones from Propargylic Alcohols through Multistep Palladium(II) Catalysis: beta-Selective Oxidative Heck Coupling of Cyclic Sulfonyl Enamides and Aryl Boroxines2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 51, p. 13745-13750Article in journal (Refereed)
  • 5.
    Ankner, Tobias
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cosner, Casey C.
    Helquist, Paul
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium- and Nickel-Catalyzed Alkenylation of Enolates2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 6, p. 1858-1871Article, review/survey (Refereed)
    Abstract [en]

    Transition-metal-catalyzed alkenylation of enolates provides a direct method to synthesize broadly useful ,-unsaturated carbonyl compounds from the corresponding carbonyl compound and alkenyl halides. Despite being reported in the early seventies, this reaction class saw little development for many years. In the past decade, however, efforts to develop this reaction further have increased considerably, and many research groups have reported efficient coupling protocols, including enantioselective versions. These reactions most commonly employ palladium catalysts, but there are also some important reports using nickel. There are many examples of this powerful transformation being used in the synthesis of complex natural products.

  • 6.
    Babu, Beneesh P.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Meng, Xu
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Aerobic Oxidative Coupling of Arenes and Olefins through a Biomimetic Approach2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 13, p. 4140-4145Article in journal (Refereed)
  • 7.
    Bartholomeyzik, Teresa
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium(II)-Catalyzed Oxidative Carbocyclization/Functionalization of Allenynes2013Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Palladium catalysis has emerged as an outstanding tool in synthetic organic chemistry for the mild and selective formation of carbon-carbon and carbon-heteroatom bonds. This thesis has been directed towards the extension of palladium(II)-catalyzed carbocyclization chemistry under oxidative conditions. An oxidative carbocyclization/functionalization methodology utilizing boron-containing transmetalation reagents was exploited to convert 1,5-allenynes into either arylated or borylated carbocycles. Two protocols were developed that use minimal amounts of Pd(OAc)2, stoichiometric para-benzoquinone as the oxidant and either bis(pinacolato)diboron or different arylboronic acids under mild conditions. A wide substrate scope is applicable to both methods. When the allenyne substrate bears a propargylic hydrogen, two isomeric functionalized carbocycles can be formed. By controlling the reaction conditions the reaction can be directed towards either of these two isomeric products. Kinetic isotope effect studies suggest that the mechanism leading to the different products proceeds through allylic or propargylic C-H bond cleavage, respectively. Moreover, it was observed that water has an interesting effect on the product selectivity when arylboronic acids are used in the oxidative carbocyclization of allenynes.

  • 8.
    Bartholomeyzik, Teresa
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Deng, Youqian
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Selective Palladium-catalyzed oxidative carbocyclization of allenynes2013In: Abstracts of Papers of The American Chemical Society, American Chemical Society (ACS), 2013Conference paper (Other academic)
  • 9. Biswas, Srijit
    et al.
    Dahlstrand, Christian
    Watile, Rahul A.
    Kalek, Marcin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Samec, Joseph S. M.
    Atom-Efficient Gold(I)-Chloride-Catalyzed Synthesis of alpha-Sulfenylated Carbonyl Compounds from Propargylic Alcohols and Aryl Thiols: Substrate Scope and Experimental and Theoretical Mechanistic Investigation2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 52, p. 17939-17950Article in journal (Refereed)
    Abstract [en]

    Gold(I)-chloride-catalyzed synthesis of -sulfenylated carbonyl compounds from propargylic alcohols and aryl thiols showed a wide substrate scope with respect to both propargylic alcohols and aryl thiols. Primary and secondary aromatic propargylic alcohols generated -sulfenylated aldehydes and ketones in 60-97% yield. Secondary aliphatic propargylic alcohols generated -sulfenylated ketones in yields of 47-71%. Different gold sources and ligand effects were studied, and it was shown that gold(I) chloride gave the highest product yields. Experimental and theoretical studies demonstrated that the reaction proceeds in two separate steps. A sulfenylated allylic alcohol, generated by initial regioselective attack of the aryl thiol on the triple bond of the propargylic alcohol, was isolated, evaluated, and found to be an intermediate in the reaction. Deuterium labeling experiments showed that the protons from the propargylic alcohol and aryl thiol were transferred to the 3-position, and that the hydride from the alcohol was transferred to the 2-position of the product. Density functional theory (DFT) calculations showed that the observed regioselectivity of the aryl thiol attack towards the 2-position of propargylic alcohol was determined by a low-energy, five-membered cyclic protodeauration transition state instead of the strained, four-membered cyclic transition state found for attack at the 3-position. Experimental data and DFT calculations supported that the second step of the reaction is initiated by protonation of the double bond of the sulfenylated allylic alcohol with a proton donor coordinated to gold(I) chloride. This in turn allows for a 1,2-hydride shift, generating the final product of the reaction.

  • 10.
    Blomberg, Margareta R. A.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Siegbahn, Per E. M.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Why is the reduction of NO in cytochrome c dependent nitric oxide reductase (cNOR) not electrogenic?2013In: Biochimica et Biophysica Acta - Bioenergetics, ISSN 0005-2728, E-ISSN 1879-2650, Vol. 1827, no 7, p. 826-833Article in journal (Refereed)
    Abstract [en]

    The membrane-bound enzyme cNOR (cytochrome c dependent nitric oxide reductase) catalyzes the reduction of NO in a non-electrogenic process. This is in contrast to the reduction of O-2 in cytochrome c oxidase (CcO), the other member of the heme-copper oxidase family, which stores energy by the generation of a membrane gradient. This difference between the two enzymes has not been understood, but it has been speculated to be of kinetic origin, since per electron the NO reduction is more exergonic than the O-2 reduction, and the energy should thus be enough for an electrogenic process. However, it has not been clear how and why electrogenicity, which mainly affects the thermodynamics, would slow down the very exergonic NO reduction. Quantum chemical calculations are used to construct a free energy profile for the catalytic reduction of NO in the active site of cNOR. The energy profile shows that the reduction of the NO molecules by the enzyme and the formation of N2O are very exergonic steps, making the rereduction of the enzyme endergonic and rate-limiting for the entire catalytic cycle. Therefore the NO reduction cannot be electrogenic, i.e. cannot take electrons and protons from the opposite sides of the membrane, since it would increase the endergonicity of the rereduction when the gradient is present, thereby increasing the rate-limiting barrier, and the reaction would become too slow. It also means that proton pumping coupled to electron transfer is not possible in cNOR In CcO the corresponding rereduction of the enzyme is very exergonic.

  • 11. Chassagne, Pierre
    et al.
    Fontana, Carolina
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Guerreiro, Catherine
    Gauthier, Charles
    Phalipon, Armelle
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mulard, Laurence A.
    Structural Studies of the O-Acetyl-Containing O-Antigen from a Shigella flexneri Serotype 6 Strain and Synthesis of Oligosaccharide Fragments Thereof2013In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 19, p. 4085-4106Article in journal (Refereed)
    Abstract [en]

    Extensive analysis by NMR spectroscopy of the delipidated lipopolysaccharide of Shigella flexneri serotype 6 strain MDC 2924-71 confirmed the most recently reported structure of the O-antigen repeating unit as {4)--D-GalpA-(13)--D-GalpNAc-(12)--L-Rhap3Ac/4Ac-(12)--L-Rhap-(1}, and revealed the non-stoichiometric acetylation at O-3C/4C. Input from the CASPER program helped to ascertain the fine distribution of the three possible patterns of O-acetylation. The non-O-acetylated repeating unit (ABCD) corresponded to about 2/3 of the population, while 1/4 was acetylated at O-3C (3AcCDAB), and 1/10 at O-4C (4AcCDAB). Di- to tetrasaccharides with a GalpA residue (A) at their reducing end were synthesized as their propyl glycosides following a multistep linear strategy relying on late-stage acetylation at O-3C. Thus, the 3C-O-acetylated and non-O-acetylated targets were synthesized from common protected intermediates. Rhamnosylation was most efficiently achieved by using imidate donors, including at O-4 of a benzyl galacturonate acceptor. In contrast, a thiophenyl 2-deoxy-2-trichloroacetamido-D-galactopyranoside precursor was preferred for chain elongation involving residue B. Final Pd/C-mediated deprotection ensured O-acetyl stability. All of the target molecules represent parts of the O-antigen of S. flexneri 6, a prevalent serotype. Non-O-acetylated oligosaccharides are also fragments of the Escherichia coli O147 O-antigen.

  • 12.
    Chen, Hong
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Deng, Youqian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Yu, Zhengbao
    Zhao, Huishuang
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Yao, Qingxia
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Zou, Xiaodong
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    3D Open-Framework Vanadoborate as a Highly Effective Heterogeneous Pre-catalyst for the Oxidation of Alkylbenzenes2013In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 25, no 24, p. 5031-5036Article in journal (Refereed)
    Abstract [en]

    Three three-dimensional (3D) open-framework vanadoborates, denoted as SUT-6-Zn, SUT-6-Mn, and SUT-6-Ni, were synthesized using diethylenetriamine as a template. SUT-6-Zn, SUT-6-Mn, and SUT-6-Ni are isostructural and built from (VO)(12)O-6 B18O36(OH)(6) clusters bridged by ZnO5, MnO6, and NiO6 polyhedra, respectively, to form the 3D frameworks. SUT-6 is the first vanadoborate with a 3D framework. The framework follows a semiregular hxg net topology with a 2-fold interpenetrated diamond-like channel system. The amount of template used in the synthesis played an important role in the dimensionality of the resulting vanadoborate structures. A small amount of diethylenetriamine led to the formation of this first 3D vanadoborate framework, while an increased amount of diethylenetriamine resulted in vanadoborates with zero-dimensional (0D) and one-dimensional (1D) structures. SUT-6-Zn was proved to be an efficient heterogeneous precatalyst for the oxidation of alkylbenzenes.

  • 13. Coll, Mercedes
    et al.
    Pamies, Oscar
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Dieguez, Montserrat
    Second-Generation Amino Acid Furanoside Based Ligands from D-Glucose for the Asymmetric Transfer Hydrogenation of Ketones2013In: ChemCatChem, ISSN 1867-3880, E-ISSN 1867-3899, Vol. 5, no 12, p. 3821-3828Article in journal (Refereed)
    Abstract [en]

    A novel series of modular amino acid thioamide ligands functionalized with carbohydrates were introduced and employed in the rhodium-catalyzed asymmetric transfer hydrogenation (ATH) of aryl alkyl ketones, including the less-studied heteroaromatic ketones. The ligands are based on amino acid hydroxyamides (pseudodipeptides), which are the most successful ligands previously used in asymmetric hydrogen transfer reactions. High enantioselectivities [up to 99% enantiomeric excess (ee)] were achieved in the ATH of a wide range of aryl alkyl ketones by using catalysts generated insitu from [RhCl2Cp*](2) (Cp*=C5Me5) and thioamide ligands comprising a 3-benzyl glucofuranoside backbone and a bulky isopropyl group in the -amino acid moiety. Interestingly, both enantiomers of the alcohol products can readily be obtained with high enantioselectivity by simply changing the absolute configuration of the -amino acid. The good performance can be extended to a very challenging class of industrially interesting heteroaromatic ketones (up to 99%ee).

  • 14. Cosner, Casey C.
    et al.
    Iska, Vijaya Bhaskara Reddy
    Chatterjee, Anamitra
    Markiewicz, John T.
    Corden, Steven J.
    Löfstedt, Joakim
    Ankner, Tobias
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Richer, Joshua
    Hulett, Tyler
    Schauer, Douglas J.
    Wiest, Olaf
    Helquist, Paul
    Evolution of Concise and Flexible Synthetic Strategies for Trichostatic Acid and the Potent Histone Deacetylase Inhibitor Trichostatin A2013In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 1, p. 162-172Article in journal (Refereed)
    Abstract [en]

    (R)-(+)-Trichostatic acid and (R)-(+)-trichostatin A (TSA) are natural products that have attracted considerable attention in the field of epigenetic therapies. TSA in particular is a naturally occurring hydroxamic acid having potent activity as a histone deacetylase inhibitor (HDACi) and having significant potential for treatment of a myriad of genetically based diseases. Development of TSA and other trichostatic acid derivatives into useful small-molecule therapies has been hindered by the low natural abundance and high cost associated with these compounds. We report herein our collective efforts towards the development of concise and scalable routes for the synthesis of trichostatic acid and TSA in both racemic and enantioenriched forms. Three independent synthetic pathways were developed with varying degrees of efficiency and convergency. In the first synthesis, the key step was a vinylogous Horner-Wadsworth-Emmons condensation. A Marshall propargylation reaction was used as the key step in the second synthesis, and Pd-catalyzed a-alkenylation of a ketone zinc enolate by using various functionalized alkenyl or dienyl halides was developed for the third synthesis. The second pathway proved to be readily amenable to an enantioselective modification, and both the second and third pathways were straightforwardly adapted for the facile preparation of new analogues of trichostatic acid and TSA.

  • 15.
    Deng, Youqian
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium-Catalyzed Oxidative Acyloxylation/Carbocyclization of Allenynes2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 11, p. 3217-3221Article in journal (Refereed)
  • 16.
    Deng, Youqian
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Teresa, Bartholomeyzik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Control of Selectivity in Palladium-Catalyzed Oxidative Carbocyclization/Borylation of Allenynes2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 24, p. 6283-6287Article in journal (Refereed)
    Abstract [en]

    In control: A highly selective carbocyclization/borylation of allenynes with bis(pinacolato)diboron (B2pin2) under palladium catalysis and with p-benzoquinone (BQ) as the oxidant was developed. The use of either LiOAc⋅2 H2O with 1,2-dichloroethane (DCE) as the solvent or BF3⋅Et2O together with THF is crucial for the selective formation of borylated trienes and vinylallenes, respectively.

  • 17.
    Engström, Karin
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Johnston, Eric V.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Verho, Oscar
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Gustafson, Karl P. J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Shakeri, Mozaffar
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Tai, Cheuk-Wai
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Co-immobilization of an Enzyme and a Metal into the Compartments of Mesoporous Silica for Cooperative Tandem Catalysis: An Artificial Metalloenzyme2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 52, p. 14006-14010Article in journal (Refereed)
    Abstract [en]

    Surpassing nature: A hybrid catalyst in which Candida antarctica lipase B and a nanopalladium species are co-immobilized into the compartments of mesoporous silica is presented. The metal nanoparticles and the enzyme are in close proximity to one another in the cavities of the support. The catalyst mimics a metalloenzyme and was used for dynamic kinetic resolution of a primary amine in high yield and excellent enantioselectivity.

  • 18.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Carbohydrate dynamics and interactions studied by NMR spectroscopy2013Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The combination of NMR spectroscopy and molecular dynamics (MD) simulations are powerful tools in the studying of bioorganic molecules in solution. In this thesis two such studies are presented with focus on the NMR aspect. The caffeine association to sugars (D-glucose and sucrose) was investigated by NMR titrations and NOESY experiments in paper I. The observations from the NMR experiments confirmed MD simulations showing that the binding occurs by a face-to-face interaction between the aromatic surface of the caffeine and axial protons of the sugar ring. Different sugar molecules and residues have different preferences regarding which side of the sugar ring that are involved in the binding. The sucrose residues bind with only one ring face each whereas β-D-glucopyranose has two sides of similar binding probability and the α-D-glucopyranose has something in between. The MD simulations showed that the driving force of the binding is partly driven by hydration effects that favor the enthalpy of the system. A new approach to calculate NMR relaxation parameters (that is dependent on molecular motions) from computational simulations is presented in paper II. Each sugar residue is assumed to be a rigid unit connected by flexible joints in the approach, thus the name diffusive chain model (DCM). The simplified model together with a stochastic simulation approach lowers the computational cost which makes it possible to acquire long enough trajectories to the calculations of spin relaxation parameters. Two case studies with slightly different methodologies are presented. In one of them, spin relaxation parameters are reproduced for the human milk oligosaccharide LNF-1 in a feasible way by the use of Brownian dynamics.

  • 19.
    Eriksson, Kristofer
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Gothelid, Emmanuelle
    Puglia, Carla
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Oscarsson, Sven
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Performance of a biomimetic oxidation catalyst immobilized on silica particles2013In: Journal of Catalysis, ISSN 0021-9517, E-ISSN 1090-2694, Vol. 303, p. 16-21Article in journal (Refereed)
    Abstract [en]

    A biomimetic oxidation catalyst, cobalt porphyrin with thiol linkers, was chemically conjugated to silica particles and utilized in the oxidation of hydroquinone to benzoquinone. The cobalt porphyrin/silica particle catalyst was characterized with Inductively Coupled Plasma (ICP) and X-ray Photoelectron Spectroscopy (XPS). The catalytic performance of the cobalt porphyrin molecules was compared to previous results for the same catalyst grafted to a gold surface and on silicon wafers. The measured catalytic activity, after background correction, was 100 times higher than that of its homogeneous counterpart, 10 times higher than that on a silicon wafer, and almost the same as that on a gold surface. The turnover frequency rates after 400 h are still comparable with initial rates reported for homogeneous porphyrins and salophens, whereas the use of particles as support increases the active surface area, which removes the limitations for scale-up associated with the previously used silicon wafers and gold surfaces.

  • 20.
    Fontana, Carolina
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    NMR spectroscopy in structural and conformational analysis of bacterial polysaccharides2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Carbohydrates constitute one of the three major classes of biomolecules found in all living cells and, unlike nucleic acids and proteins, their polymeric structures are not based on a template. The structural diversity of these molecules confers them an enormous capacity to encode information in biological systems, acting as efficient mediators in the interaction of the cell with the environment. In order to understand the roles of glycans in biological processes it is of key importance to have a detailed understanding of their structures and conformational preferences, and NMR spectroscopy is one of most powerful techniques for the study of these molecules in solution.

    This thesis is focused on the structural and conformational analysis of lipopolysaccharides from Gram-negative bacteria. In the first two projects (Chapter 2 and 3) the structural analyses of the biological repeating units of the O-antigen polysaccharides from E. coli O174ab and O115 are described; in both cases a combination of NMR spectroscopy and gas chromatography techniques were used. Special emphasis was made in the characterization of the O-acetylation patterns observed in the native O-antigen polysaccharide from E. coli O115. Chapter 4 describes the development of a new methodology for the determination of the absolute configuration of monosaccharide components of glycans. This methodology was used in the structural elucidation of the O-antigen PS of E. coli O155 (Chapter 5) that was carried out in a semi-automated manner using the program CASPER and unassigned NMR data. The conformational preferences of O-antigen PS of E. coli O5ac and O5ab are analyzed in Chapter 6, using a combination of NMR spectroscopy and molecular modeling methods. In Chapter 7 the structural analysis is focused on the core region of the LPS, and the structures of the deacylated lipooligosaccharides of three rough mutants of B. melitesis are reported. In several of the aforementioned chapters, the biosynthetic aspects behind the assembly of the respective PSs were examined on the bases of genetic information available in the NCBI and ECODAB databases.  Finally, in Chapter 8, different NMR pulse sequences available for the study of proteins and nucleic acids were evaluated and optimized for the structural analysis of 13C uniformly-labeled oligo- and polysaccharides.

  • 21.
    Fontana, Carolina
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ramström, Kristoffer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Weintraub, Andrej
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Structural studies of the O-antigen polysaccharide from Escherichia coli O115 and biosynthetic aspects thereof2013In: Glycobiology, ISSN 0959-6658, E-ISSN 1460-2423, Vol. 23, no 3, p. 354-362Article in journal (Refereed)
    Abstract [en]

    The structure of the O-antigen polysaccharide (PS) of Escherichia coliO115 has been investigated using a combination of component analysis and 1D and 2D nuclear magnetic resonance (NMR) spectroscopy experiments. The repeating unit of the O-antigen was elucidated using the O-deacetylated PS and has the following branched pentasaccharide structure: →3)[β-L-Rhap-(1 → 4)]-β-D-GlcpNAc-(1 → 4)-α-D-GalpA-(1 → 3)-α-D-Manp-(1 → 3)-β-D-GlcpNAc-(1→. Cross-peaks of low intensity, corresponding to a β-L-Rhap-(1 → 4)-β-D-GlcpNAc-(1→ structural element, were present in the NMR spectra and attributed to the terminal part of the PS; this information defines the biological repeating unit of the O-antigen by having a 3-substituted N-acetyl-D-glucosamine (GlcNAc) residue at its reducing end. Analysis of the NMR spectra of the native PS revealed O-acetyl groups distributed over different positions of theL-Rhap residue (∼0.70 per repeating unit) as well as at O-2 and O-3 of the D-GalpA residue (∼0.03 and ∼0.25 per repeating unit, respectively), which is in agreement with the presence of two acetyltransferases previously identified in the O-antigen gene cluster (Wang Q, Ruan X, Wei D, Hu Z, Wu L, Yu T, Feng L, Wang L. 2010. Mol Cell Probes. 24:286–290.). In addition, the four glycosyltransferases initially identified in the O-antigen gene cluster of E. coli O115 were analyzed using BLAST, and the function of two of them predicted on the basis of similarities with glycosyltransferases from Shigella dysenteriae type 5 and 12, as well as E. coli O58 and O152.

  • 22. George, Riham F.
    et al.
    Ismail, Nasser S. M.
    Stawinski, Jacek
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Girgis, Adel S.
    Design, synthesis and QSAR studies of dispiroindole derivatives as new antiproliferative agents2013In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 68, p. 339-351Article in journal (Refereed)
    Abstract [en]

    A variety of 4'-ary1-3-(arylmethylidene)-1 ''-[(cyclic-amino)methylene]-1'-methyl-dispiro[cyclohexane-1,3'-pyrrolidine-2',3 ''-[3H]indole]-2,2 ''(1H)-diones 4a-u were prepared via reaction of 2E,6E-bis(arylidene)-1-cyclohexanones 1a-i with azomethine ylides, generated in situ via a decarboxylative condensation of isatins 2a-c and sarcosine (3). Single crystal X-ray study of 4a, revealed structural and stereochemical features of these derivatives. While most of the synthesized compounds exhibit mild antitumor properties when tested against various human tumor cell lines (HEPG2 liver, HELA cervical and PD prostate cancers), three of them, 4d and 4p (active against HEPG2), and compound 4g (active against HELA), demonstrated higher activities, that were close or even higher than that of the reference standard Doxorubicin. QSAR studies revealed good predictive and statistically significant 3 descriptor models (r(2) = 0.903-0.812, r(adjusted)(2) = 0.855-0.672, r(prediction)(2) = 0.773-0.605).

  • 23.
    Gigant, Nicolas
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of Conjugated Dienes via a Biomimetic Aerobic Oxidative Coupling of Two CvinylH Bonds2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 33, p. 10799-10803Article in journal (Refereed)
    Abstract [en]

    A time to dienes: A highly efficient and general method has been developed to prepare conjugated dienes through a biomimetic approach. This aerobic oxidative coupling, involving two CvinylH bonds, proceeds under low Pd catalyst loading and employs catalytic amounts of p-benzoquinone and iron phthalocyanine as electron-transfer mediators (ETMs) under ambient oxygen pressure (see scheme).

  • 24. 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.

  • 25.
    Huang, Genping
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kalek, Marcin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mechanism and Selectivity of Rhodium-Catalyzed 1:2 Coupling of Aldehydes and Allenes2013In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 135, no 20, p. 7647-7659Article in journal (Refereed)
    Abstract [en]

    The rhodium-catalyzed highly regioselective 1:2 coupling of aldehydes and allenes was investigated by means of density functional theory calculations. Full free energy profiles were calculated, and several possible reaction pathways were evaluated. It is shown that the energetically most plausible catalytic cycle is initiated by oxidative coupling of the two allenes, which was found to be the rate-determining step of the overall reaction. Importantly, Rh allyl complexes that are able to adopt both eta(3) and eta(1) configurations were identified as key intermediates present throughout the catalytic cycle with profound implications for the selectivity of the reaction. The calculations reproduced and rationalized the experimentally observed selectivities and provided an explanation for the remarkable alteration in the product distribution when the catalyst precursor is changed from [RhCl(nbd)](2) (nbd = norbornadiene) to complexes containing noncoordinating counterions ([Rh(cod)(2)X]; X = OTf, BF4, PF6; cod = 1,5-cyclooctadiene). It turns out that the overall selectivity of the reaction is controlled by a combination of the inherent selectivities of several of the elementary steps and that both the mechanism and the nature of the selectivity-determining steps change when the catalyst is changed.

  • 26. Ibrahem, Ismail
    et al.
    Ma, Guangning
    Afewerki, Samson
    Cordova, Armando
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium/chiral amine co catalyzed enantioselective beta arylation of alpha,beta unsaturated aldehydes2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 3, p. 878-882Article in journal (Refereed)
  • 27.
    Ilchenko, Nadia O.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Janson, Pär G.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabó, Kálmán J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Copper-Mediated Cyanotrifluoromethylation of Styrenes Using the Togni Reagent2013In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 78, no 21, p. 11087-11091Article in journal (Refereed)
    Abstract [en]

    Styrenes with an electron-deficient double bond undergo cyanotrifluoromethylation with a trifluoromethylated hypervalent iodine reagent in the presence of CuCN. The reaction proceeds under mild conditions in the presence of bulky phosphines or B(2)pin(2) additives. The process is highly regioselective and involves the consecutive formation of two C-C bonds in a single addition reaction. In the presence of a p-methoxy substituent in the styrene, oxytrifluoromethylation occurs instead of the cyanotrifluoromethylation.

  • 28.
    Ilchenko, Nadia O.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Janson, Pär
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabó, Kálmán J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Copper-mediated C-H trifluoromethylation of quinones2013In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 49, no 59, p. 6614-6616Article in journal (Refereed)
    Abstract [en]

    Quinones undergo copper-mediated C-H trifluoromethylation reactions using a hypervalent iodine reagent. The reactions have a broad synthetic scope involving naphtho, alkyl, chloro and methoxy quinones.

  • 29.
    Jiang, Liying
    et al.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Johnston, Eric
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Åberg, K. Magnus
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Nilsson, Ulrika
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Strategy for quantifying trace levels of BMAA in cyanobacteria by LC/MS/MS2013In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 405, no 4, p. 1283-1292Article in journal (Refereed)
    Abstract [en]

    The cyanobacterial neurotoxin β-N-methylamino--alanine (BMAA) is an amino acid that is putatively associated with the pathology of amyotrophic lateral sclerosis/Parkinsonism –dementia complex (ALS-PDC) disease. It raises serious health risk concerns since cyanobacteria are ubiquitous thus making human exposure almost inevitable. The identification and quantification of BMAA in cyanobacteria is challenging because it is present only in trace amounts and occurs alongside structurally similar compounds such as BMAA isomers. This work describes an enhanced liquid chromatography/tandem mass spectrometry platform that can distinguish BMAA from its isomers β-amino-N-methyl-alanine, N-(2-oethyl) glycine (AEG), and 2,4-diaminobutyric acid, thus ensuring confident identification of BMAA. The method's sensitivity was improved fourfold by a post-column addition of acetonitrile. The instrument and method limits of detection were shown to be 4.2 fmol/injection (or 0.5 g/one column) and 0.1 μg/g dry weight of cyanobacteria, respectively. The quantification method uses synthesized deuterated BMAA as an internal standard and exhibits good linearity, accuracy, and precision. Matrix effects were also investigated, revealing an ion enhancement of around 18 %. A lab-cultured cyanobacterial sample (Leptolyngbya PCC73110) was analyzed and shown to contain about 0.73 μg/g dry weight BMAA. The isomer AEG, whose chromatographic properties closely resemble those of BMAA, was also detected. These results highlight the importance of distinguishing BMAA from its isomers for reliable identification as well as providing a sensitive and accurate quantification method for measuring trace levels of BMAA in cyanobacterial samples.

  • 30.
    Jiang, Min
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium-Catalyzed Oxidative Regio- and Diastereoselective Diarylating Carbocyclization of Dienynes2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 21, p. 6571-6575Article in journal (Refereed)
  • 31.
    Kapla, Jon
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Wohlert, Jakob
    Stevensson, Baltzar
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Maliniak, Arnold
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Molecular Dynamics Simulations of Membrane-Sugar Interactions2013In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, no 22, p. 6667-6673Article in journal (Refereed)
    Abstract [en]

    It is well documented that disaccharides in general and trehalose (TRH) in particular strongly affect physical properties and functionality of lipid bilayers. We investigate interactions between lipid membranes formed by 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and TRH by means of molecular dynamics (MD) computer simulations. Ten different TRH concentrations were studied in the range W-TRH = 0-0.20 (w/w). The potential of mean force (PMF) for DMPC bilayer TRH interactions was determined using two different force fields, and was subsequently used in a simple analytical model for description of sugar binding at the membrane interface. The MD results were in good agreement with the predictions of the model. The net affinities of TRH for the DMPC bilayer derived from the model and MD simulations were compared with experimental results. The area per lipid increases and the membrane becomes thinner with increased TRH concentration, which is interpreted as an intercalation effect of the TRH molecules into the polar part of the lipids, resulting in conformational changes in the chains. These results are consistent with recent experimental observations. The compressibility modulus related to the fluctuations of the membrane increases dramatically with increased TRH concentration, which indicates higher order and rigidity of the bilayer. This is also reflected in a decrease (by a factor of 15) of the lateral diffusion of the lipids. We interpret these observations as a formation of a glassy state at the interface of the membrane, which has been suggested in the literature as a hypothesis for the membrane sugar interactions.

  • 32.
    Kärkäs, Markus
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development and Mechanistic Studies of Molecularly Defined Water Oxidation Catalysts: Catalysts for a Green and Sustainable Future2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis deals with the development of complexes that are active catalysts for H2O oxidation. Promoting proton-coupled electron transfer has been a highly important feature in the development of these catalysts.

    The first part deals with the modification of ligand frameworks for the development of a ruthenium complex capable of withstanding the highly oxidizing conditions required for H2O oxidation. 

    The second part of the thesis describes the development of two single-site ruthenium(III) complexes, housing two meridionally coordinating tridentate benzimidazole ligands. Studies on these complexes revealed that they can mediate H2O oxidation, both by the use of a chemical oxidant and photochemically, and that the ligand frameworks were important in promoting proton-coupled electron transfer events.

    In the third part, systematic modifications are introduced into one of the catalysts developed in the second part of the thesis. All of the complexes were shown to be active water oxidation catalysts (WOCs), and kinetic studies confirmed that all catalysts displayed a first-order dependence on catalyst concentration, thereby validating that H2O oxidation occurs on a single metal site. By using linear free-energy relationships it was possible to elucidate the unusual behavior exerted by the ligand framework during the catalytic cycle.

    The fourth part concerns the development of a ruthenium(III) WOC, containing a tetradentate bioinspired ligand architecture, and its deactivation pathway during H2O oxidation catalysis. This revealed an unexplored, and perhaps general, deactivation pathway for ruthenium-based WOCs. Evidence was also found that the ruthenium WOC reaches a high-valent ruthenium(VI) state which is the active species in H2O oxidation.

    Finally, the fifth and last part deals with the development of a dinuclear manganese complex. Utilizing a bioinspired, highly functionalized ligand, enabled the formation of the first homogeneous manganese-based WOC capable of promoting catalytic H2O oxidation with one-electron oxidants.

  • 33.
    Kärkäs, Markus D.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Åkermark, Torbjörn
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Chen, Hong
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). China University of Geosciences .
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Åkermark, Björn
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    A Tailor-Made Molecular Ruthenium Catalyst for the Oxidation of Water and Its Deactivation through Poisoning by Carbon Monoxide2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 15, p. 4189-4193Article in journal (Refereed)
  • 34.
    Larsson, Johanna M.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pathipati, Stalin R.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabó, Kálmán J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Regio- and Stereoselective Allylic Trifluoromethylation and Fluorination using CuCF3 and CuF Reagents2013In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 78, no 14, p. 7330-7336Article in journal (Refereed)
    Abstract [en]

    Copper-mediated trifluoromethylation of allylic chlorides and trifluoroacetates was performed using a convenient Cu-CF3 reagent. The reaction is suitable for selective synthesis of allyl trifluoromethyl species. Mechanistic studies indicate that the reaction proceeds via a nucleophilic substitution mechanism involving allyl copper intermediates. The analogous Cu-F reagent was suitable for fluorination of allyl chlorides. Stereodefined cyclic substrates reacted regio- and stereoselectively.

  • 35.
    Larsson, Johanna M.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabo, Kalman J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mechanistic Investigation of the Palladium-Catalyzed Synthesis of Allylic Silanes and Boronates from Allylic Alcohols2013In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 135, no 1, p. 443-455Article in journal (Refereed)
    Abstract [en]

    The mechanism of the palladium-catalyzed synthesis of allylic silanes and boronates from allylic alcohols was investigated. H-1, Si-29, F-19, and B-11 NMR spectroscopy was used to reveal key intermediates and byproducts of the silylation reaction. The tetrafluoroborate counterion of the palladium catalyst is proposed to play an important role in both catalyst activation as well as the transmetalation step. We propose that BF3 is generated in both processes and is responsible for the activation of the substrate hydroxyl group. An (eta(3)-allyl)palladium complex has been identified as the catalyst resting state, and the formation of (eta(3)-allyl)palladium complexes directly from allylic alcohols has been studied. Kinetic analysis provides evidence that the turnover limiting step is the transmetalation, and insights into notable similarities between the borylation and the silylation reaction mechanisms enabled us to considerably improve the stereoselectivity of the borylation.

  • 36.
    Lee, Bao-Lin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development of metal complexes for water oxidation2013Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In an artificial version of photosynthesis, sunlight and water are used to produce fuels. Our research focuses on the bottleneck in this process, the photooxidation of water. In the course of developing a water oxidation catalyst, a number of metal complexes have been synthesised, characterised, and studied for catalytic activity. Three of them are dinuclear complexes (Ru, Co and Cu) of 2,6-bis[(2-hydroxybenzyl)-(2-pyridylmethyl)aminomethyl]-4-methylphenol (H3bbpmp). The fourth is a dimeric Ru complex with a ligand containing imidazole and phenol motifs. Additionally, a dinuclear Mn complex with a ligand that contains benzimidazoles and carboxylates coordinating to the metal atoms was also developed. This Mn complex was then covalently linked to [Ru(bpy)3]2+-type photosensitisers, resulting in three different bimetallic dyads. Finally, a dinuclear Fe complex containing the same ligand as the dinuclear Mn complex was synthesised.

    The potential of the three H3bbpmp complexes as catalysts for oxidation of organic compounds was investigated and it was found that the Ru complex catalyses the oxidation of alcohols to the corresponding ketone or aldehyde using (diacetoxyiodo)benzene as oxidant. The Co complex functions as an electron transfer mediator in a coupled catalytic system for allylic oxidation using oxygen gas. The oxidation of 3,5-di-tert-butylcatechol to the corresponding ortho-quinone with oxygen gas using the copper complex proved that it can be considered as a model of catecholase. The dimeric Ru complex and the dinuclear Mn and Fe complexes proved to catalyse water oxidation when employing stoichiometric amounts of the oxidant [Ru(bpy)3](PF6)3. Furthermore, using [Ru(bpy)2(deeb)](PF6)2 as photosensitiser together with Na2S2O8 as sacrificial electron acceptor in aqueous phosphate buffer at pH = 7.2, photochemical water oxidation was demonstrated. The bimetallic dyads however, did not show catalytic activity for the oxidation of water.

  • 37.
    Lihammar, Richard
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Millet, Renaud
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Enzyme- and Ruthenium-Catalyzed Dynamic Kinetic Resolution of Functionalized Cyclic Allylic Alcohols2013In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 78, no 23, p. 12114-12120Article in journal (Refereed)
    Abstract [en]

    Enantioselective synthesis of functionalized cyclic allylic alcohols via dynamic kinetic resolution has been developed. Cyclopentadienylruthenium catalysts were used for the racemization, and lipase PS-IM or CALB was employed for the resolution. By optimization of the reaction conditions the formation of the enone byproduct was minimized, making it possible to prepare a range of optically active functionalized allylic alcohols in good yields and high ee's.

  • 38.
    Lind, Maria E. S.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Quantum Chemistry as a Tool in Asymmetric Biocatalysis: Limonene Epoxide Hydrolase Test Case2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 17, p. 4563-4567Article in journal (Refereed)
  • 39.
    Lind, Maria E.S.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Quantum Chemical Modeling of Asymmetric Enzymatic Reactions: Applications to Limonene Epoxide Hydrolase and Arylmalonate Decarboxylase2013Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, density functional theory has been employed to study the reactionmechanisms of two enzymes with possible applications in asymmetric biocatalysis.To reproduce and rationalize the stereoselectivity of the enzymes, quite large cluster models that account for the chiral environment of the active site have been used.

    In the first study, the enantioselectivity of the wild-type limonene epoxidehydrolase and two groups of mutants thereof, that show either (R,R)- or (S,S)-selectivity, were investigated. Using the cluster approach, the enantioselectivity for each variant of the enzyme was calculated and the results are in good agreement with the experimental data. It was found that the enantioselectivity of the enzyme variants is controlled by the steric hindrance introduced or relieved bythe different mutations.

    The second study concerns the reaction mechanism and stereoselectivity of arylmalonate decarboxylase. The calculations support the proposed two-step mechanism, in which decarboxylation and protonation of the substrate occur separately. The stereoselectivity of the enzyme is governed by repulsive steric interactions between the substrate and the residues that deffine a large and a small cavity in the active site. Depending on the size of the substrate, the selectivity was found to be determined already at the binding of the substrate or in the subsequent transition state.

    The results presented in this thesis demonstrate that the quantum chemical cluster approach for modeling enzymes is indeed a very valuable tool in the study of asymmetric biocatalysis.

  • 40.
    Liu, Leifeng
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Yu, Zheng-Bao
    Chen, Hong
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). China University of Geosciences, People's Republic of China .
    Deng, Youqian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lee, Bao-Lin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Peking University, People's Republic of China .
    Disorder in Extra-Large Pore Zeolite ITQ-33 Revealed by Single Crystal XRD2013In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 13, no 10, p. 4168-4171Article in journal (Refereed)
    Abstract [en]

    The single crystal of the extra-large pore zeolite, ITQ-33, was obtained and used to explore its crystal structure details. The ITQ-33 structure was found to be disordered with the columnar periodic building unit, explaining the morphology changes upon the different Si/Ge ratio, and the formation of the hierarchical structure from assembling of ITQ-33 nanofibers.

  • 41.
    Lundborg, Magnus
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ali, Eunus
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    An in silico virtual screening study for the design of norovirus inhibitors: fragment-based molecular docking and binding free energy calculations2013In: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 378, p. 133-138Article in journal (Refereed)
    Abstract [en]

    Gastrointestinal infections caused by noroviruses may be prevented by the inhibition of their binding to histo-blood group carbohydrate antigens. A fragment-based virtual screening approach was used, employing docking followed by molecular dynamics simulations in order to enable binding free energy calculations using the linear interaction energy method. The resulting structures, composed of high-affinity fragments, can be a good starting point for lead optimizations and four molecules that pass both REOS and SYLVIA filters, which can remove known toxic features and assess the synthetic accessibility, respectively, are proposed as inhibitors.

  • 42. Ma, Guangning
    et al.
    Afewerki, Samson
    Deiana, Luca
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palo-Nieto, Carlos
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Liu, Leifeng
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Inorganic and Structural Chemistry.
    Ibrahem, Ismail
    Cordova, Armando
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    A Palladium/Chiral Amine Co-catalyzed Enantioselective Dynamic Cascade Reaction: Synthesis of Polysubstituted Carbocycles with a Quaternary Carbon Stereocenter2013In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 52, no 23, p. 6050-6054Article in journal (Refereed)
  • 43.
    Malmgren, Joel
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Unsymmetrical Diaryliodonium Salts: Development and Chemoselectivity studies2013Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The first part describes a chemoselectivity study on diaryliodonium salts where oxygen, nitrogen and carbon nucleophiles have been arylated. Twelve different unsymmetric phenyl(aryl)iodonium salts were designed with a systematic variation of the steric and electronic properties of the aryl group. The chemoselectivity varies greatly between the nucleophiles but several “dummy” aryl groups were identified where selective transfer of the phenyl moiety was consequently observed. HRMS studies of the salts revealed an interesting ligand exchange between the aryl groups of the iodine under certain conditions. This will aid the understanding of the mechanism operating in diaryliodonium salt arylation reactions. The results will facilitate the design of catalytic systems employing diaryliodonium salts, as well as help in search for applications with polymer-bound salts.

    The second part of the thesis describes the development of a new synthetic route towards unsymmetric diaryliodonium salts containing one heteroaryl moiety. The substrate scope of the facile one-pot protocol involves salts containing dummy groups with large steric bulk as well as electron-rich aryl groups. The utility of the salts are demonstrated in the arylation of both phenols and malonates where selective transfer of the heteroaryl moiety was consistently observed

  • 44.
    Mobarak, Hani
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of methyl 3-amino-3,6-dideoxy-alpha-d-galactopyranoside carrying different amide substituents2013In: RSC Advances, ISSN 2046-2069, E-ISSN 2046-2069, Vol. 3, no 45, p. 23090-23097Article in journal (Refereed)
    Abstract [en]

    Bacterial polysaccharides may contain rare sugars of different stereochemistry and diverse functional groups; the repertoire can be further extended by varying the exocyclic substituents. Synthesis of four monosaccharides is described utilizing a suitably protected key intermediate obtained by regioselective acetal ring-opening reduction, dexoygenation at C6, alcohol oxidation at C3 followed by formation of an oxime, which was stereoselectively reduced by samarium diiodide to give a 3-amino-derivative having the desired galacto-configuration. Subsequent functionalization was performed resulting in one to four carbon atoms in the amide substituent.

  • 45.
    Nagendiran, Anuja
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Transition metal-catalysis: Applications of dynamic kinetic resolution in total synthesis and developments of novel methodologies using heterogeneous Pd catalysts2013Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The first part of the thesis describes a general and efficient route for the enantioselective synthesis of various α-substituted ketones and their corresponding lactones. The two key steps in this synthesis are the ruthenium and CALB-catalyzed dynamic kinetic resolution (DKR) which provided the exocyclic acetates in high yields and excellent enantioselectivity and the subsequent Cu-catalyzed α-allylic substitution giving the corresponding α-substituted products with inversed stereochemistry in high yields. This synthetic route was applied to the synthesis of the naturally occurring (R)-10-methyl-6-undecanolide, via subsequent oxidative cleavage and Baeyer-Villiger oxidation.

    In the second part, a new microwave-assisted methodology using a heterogeneous Pd nanocatalyst for Suzuki cross-couplings and hydrogenation of alkenes is presented. The catalytic system proved to be compatible with a wide range of functional groups and heteroatoms. In general, excellent yields were obtained within 45 min for the Suzuki cross-couplings and within 30 min for the hydrogenation reactions. The catalyst exhibited high recyclability with a low leaching in both cases.

    A novel method to prepare γ-alkylidene lactones from alkynoic acids mediated by a heterogeneous Pd(II) catalyst is described in the last part of the thesis. The protocol proved to be highly stereo- and regioselective, affording the 5-exo-dig lactone as the single product in all cases. In general, internal alkynes were cyclized in high to excellent yields within 3 hours using 0.3 mol% of catalyst loading. For internal alkynes, the catalyst loading had to be increased to 0.5 mol% along with prolonged reaction times and elevated temperatures in order to obtained high yields. The catalyst showed some recyclability with low leaching.

  • 46. Ostrovskis, Pavels
    et al.
    Volla, Chandra M. R.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Turks, Maris
    Markovic, Dean
    Application of Metal Free Click Chemistry in Biological Studies2013In: Current organic chemistry, ISSN 1385-2728, E-ISSN 1875-5348, Vol. 17, no 6, p. 610-640Article in journal (Refereed)
    Abstract [en]

    The first reported click reaction, copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition had limited biocompatibility due to the high toxicity of copper. Since alternative bioorthogonal click reactions have been developed, they have strongly influenced the field of chemical biology. Here are summarized three main metal-free click methodologies based on cycloaddition, Staudinger and thio-ene reactions. This review contains the basic principles, some mechanistic considerations and a collection of reagents that can be used in each method. Firstly, Diels-Alder and strain promoted inverse electron demand Diels-Alder cycloadditions are outlined together with triazole and isoxazole formation by 1,3-dipolar cycloadditions. Secondly, Staudinger-Bertozzi ligation, a chemoselective reaction of azides and engineered triarylphosphines, is discussed. Finally, thio-click chemistries including thiol-ene, thiol-yne, thio-Michael and fluoro-thio-click reactions are reviewed. Among the most important bioapplications of these click methodologies is the labeling of glycans, proteins, lipids and DNA. Additionally, synthetic methods and surface immobilization of biomolecules and biologically useful polymeric materials are also reviewed.

  • 47.
    Pendrill, Robert
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Jonsson, K. Hanna M.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Glycan synthesis, structure, and dynamics: A selection2013In: Pure and Applied Chemistry, ISSN 0033-4545, E-ISSN 1365-3075, Vol. 85, no 9, p. 1759-1770Article in journal (Refereed)
    Abstract [en]

    Glycan structural information is a prerequisite for elucidation of carbohydrate function in biological systems. To this end we employ a tripod approach for investigation of carbo hydrate 3D structure and dynamics based on organic synthesis; different experimental spectroscopy techniques, NMR being of prime importance; and molecular simulations using, in particular, molecular dynamics (MD) simulations. The synthesis of oligosaccharides in the form of glucosyl fluorides is described, and their use as substrates for the Lam16A E115S glucosyl synthase is exemplified as well as a conformational analysis of a cyclic beta-(1 -> 3)-heptaglucan based on molecular simulations. The flexibility of the N-acetyl group of aminosugars is by MD simulations indicated to function as a gatekeeper for transitions of glycosidic torsion angles to other regions of conformational space. A novel approach to visualize glycoprotein (GP) structures is presented in which the protein is shown by, for example, ribbons, but instead of stick or space-filling models for the carbohydrate portion it is visualized by the colored geometrical figures known as CFG representation in a 3D way, which we denote 3D-CFG, thereby effectively highlighting the sugar residues of the glycan part of the GP and the position(s) on the protein.

  • 48.
    Pu, Maoping
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Privalov, Timofei
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ab initio dynamics trajectory study of the heterolytic cleavage of H2 by a Lewis acid [B(C6F5)3] and a Lewis base [P(tBu)3]2013In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 138, no 15, article id 154305Article in journal (Refereed)
    Abstract [en]

    Activation of H-2 by a frustrated Lewis pair (FLP) composed of B(C6F5)(3) and P(tBu)(3) species has been explored with high level direct ab initio molecular dynamics (AIMD) simulations at finite temperature (T = 300 K) in gas phase. The initial geometrical conditions for the AIMD trajectory calculations, i.e., the near attack conformations of FLP + H-2, were devised using the host-guest model in which suitable FLP conformations were obtained from the dynamics of the B(C6F5)(3)/P(tBu)(3) pair in gas phase. AIMD trajectory calculations yielded microscopic insight into effects which originate from nuclear motion in the reacting complex, e. g., the alternating compression/elongation of the boron-phosphorous distance and the change of the pyramidality of boron in B(C6F5)(3). The ensemble averaged trajectory analysis has been compared with the minimum energy path (MEP) description of the reaction. Similar to MEP, AIMD shows that an attack of the acid/base pair on the H-H bond gives rise to the polarization of the H-2 molecule and as a consequence generates a large dipole moment of the reacting complex. The MEP and AIMD portrayals of the reaction are fundamentally different in terms of the magnitude of the motion of nuclei in B(C6F5)(3) and P(tBu)(3) during the H-2 cleavage. In the AIMD trajectory simulations, geometries of B(C6F5)(3) and P(tBu)(3) appear as nearly frozen on the short time scale of the H-2 cleavage. This is contrary to the MEP picture. Several of the concepts which arise from this work, e. g., separation of time scales of nuclear motion and the time-dependence of the donor-acceptor interactions in the reacting complex, are important for the understanding of chemical reactivity and catalysis.

  • 49.
    Pu, Maoping
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Privalov, Timofei
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Binding of CO2 by a Mes(2)PCH(2)CH(2)B(C6F5)(2) Species: An Involvement of the Ground State Species in a Low-Energy Pathway2013In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 19, no 49, p. 16512-16517Article in journal (Refereed)
  • 50.
    Rudbeck, Maria E.
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Blomberg, Margareta R. A.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Barth, Andreas
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Hydrolysis of the E2P Phosphoenzyme of the Ca2+-ATPase: A Theoretical Study2013In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 117, no 31, p. 9224-9232Article in journal (Refereed)
    Abstract [en]

    Dephosphorylation of the E2P phosphoenzyme intermediate of the sarcoplasmic reticulum Ca2+-ATPase was studied using density functional theory. The hydrolysis reaction proceeds via a nucleophilic attack on the phosphorylated residue Asp351 by a water molecule, which is positioned by the nearby residue Glu183 acting as a base. The activation barrier was calculated to be 14.3 kcal/mol, which agrees well with values of 15-17 kcal/mol derived from experimentally observed rates. The optimized structure of the transition state reveals considerable bond breakage between phosphorus and the Asp351 oxygen (distance 2.19 angstrom) and little bond formation to the attacking water oxygen (distance 2.26 angstrom). Upon formation of the singly protonated phosphate product, Glu183 becomes protonated. The bridging aspartyl phosphate oxygen approaches Lys684 progressively when proceeding from the reactant state (distance 1.94 angstrom) via the transition state (1.78 angstrom) to the product state (1.58 angstrom). This stabilizes the negative charge that develops on the leaving group. The reaction was calculated to be slightly endergonic (+0.9 kcal/mol) and therefore reversible, in line with experimental findings. It is catalyzed by a preorganized active site with little movement of the nonreacting groups except for a rotation of Thr625 toward the phosphate group.

12 1 - 50 of 68
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf