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  • 1.
    Andersson, P.G.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Development of New Methodology for th Preparation of Optically Active Alcohols2004In: Pure Appl. Chem., no 76, p. 547-Article in journal (Refereed)
  • 2.
    Andersson, Pher
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Development of a new methodology for the preparation of optically active alcohols*2004In: Pure Appl. Chem., Vol. 76, no 3, p. 547-555Article in journal (Refereed)
  • 3.
    Balan, Daniela
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    The three-component aza-Baylis-Hillman reaction: development and application2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The current thesis presents the optimization and generalization of the Baylis-Hillman reaction applied to in situ generated imines, i.e. a three-component aza- Baylis-Hillman reaction. We found that the title reaction proceeds most efficiently in the presence of a combination of catalysts, i.e. 3-hydroxyquinuclidine (0.15 equiv) and titanium isopropoxide (0.02 equiv), together with molecular sieves (4 Å; activated powder; 200 mg/mmol substrate) at ambient temperature.

    Our study of the scope and limitations of this reaction, revealed that arylaldehydes and sulfonamides are the only imine precursors which both generate the corresponding imines in situ and facilitate a further reaction with the Michael acceptor in a Baylis-Hillman fashion. Among the Michael acceptors tested, acrylates and acrylonitrile demonstrate high reactivity, while acrylamides and β-substituted acrylates do not participate in the reaction.

    The optimized conditions applied to the above range of substrates results in good-to-excellent yields of the desired amine-products (53-94%) and very high chemoselectivity (83- >99%). Furthermore, the reaction times observed under these conditions are considerably shorter than those previously reported for the aza-Baylis-Hillman reaction.

    In the development of a stereoselective version of the title reaction, the use of a chiral catalyst proved to be most effective. Thus, an enantiomeric excess up to 74% can be obtained with β-Isocupreidine. With chiral imine precursors or chiral acrylates, the diastereoselectivity attained was poor. No asymmetric induction was observed when chiral Lewis acids were employed as a co-catalyst.

    The α-methylene-β-amino acid derivatives obtained via the three-component aza-Baylis-Hillman reaction were subjected to further transformation. Carbon chain elongation at the olefinic end of the amine-adduct was attempted. For this purpose, the Miyaura borylation protocol could be successfully applied. The subsequent Suzuki-type cross-coupling reaction resulted predominantly in hydrolysis of the boronate intermediate, together with formation of the amine-adduct via β-hydride elimination. The optimal conditions for this latter reaction remain to be found.

    Finally, 2,5-dihydropyrroles have been synthesized from aza-Baylis-Hillman adducts, via a short and efficient route in which the key step is a microwave-assisted ring-closing metathesis of the N-allylated amine-adducts.

  • 4.
    Baltzer, Lars
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    DeGrado, W. F.
    Engineering and design: Expanding the protein world2004In: Editorial overview Current Opinion of Structural Biology, Vol. 14, p. 455-457Article, review/survey (Other (popular scientific, debate etc.))
  • 5. Beletskaya, I.P
    et al.
    Bregadze, V.I.
    Ivushkin, V.A.
    Petrovskii, P.V.
    Sivaev, I.B.
    Sjöberg, Stefan
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    Zhigareva, G.B.
    New B-substituted derivatives of m-carborane, p-carborane, and cobalt bis(1,2-decarbollide) anion2004In: J. Organomet. Chem., no 689, p. 2920-Article in journal (Refereed)
  • 6. Brandt, Peter
    et al.
    Roth, Peter
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Andersson, Pher
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Origin of Enantioselectivity in the Ru(arene)(amino alcohol)-Catalyzed Transfer Hydrogenation of Ketones2004In: J. Org. Chem., no 69, p. 4885-4890Article in journal (Refereed)
    Abstract
  • 7.
    Bruskin, Alexander
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sivaev, Igor
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    Persson, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Carlsson, Jörgen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sjöberg, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Radiobromination of monoclonal antibody using potassium [76Br] (4 isothiocyanatobenzyl-ammonio)-bromo-decahydro-closo-dodecaborate (Bromo-DABI)2004In: Nuclear Medicine and Biology, ISSN 0969-8051, E-ISSN 1872-9614, Vol. 31, no 2, p. 205-11Article in journal (Refereed)
    Abstract [en]

    The use of charged linkers in attaching radiohalogens to tumor-seeking biomolecules may improve intracellular retention of the radioactive label after internalization and degradation of targeting proteins. Derivatives of polyhedral boron clusters, such as closo-dodecaborate (2-) anion, might be possible charged linkers. In this study, a bifunctional derivative of closo-dodecaborate, (4-isothiocyanatobenzyl-ammonio)-undecahydro-closo-dodecaborate (DABI) was labeled with positron-emitting nuclide (76)Br (T 1/2 = 16.2 h) and coupled to anti-HER2/neu humanized antibody Trastuzumab. The overall labeling yield at optimized conditions was 80.7 +/- 0.6%. The label was proven to be stable in vitro in physiological and a set of denaturing conditions. The labeled antibody retained its capacity to bind to HER-2/neu antigen expressing cells. The results of the study demonstrated feasibility for using derivatives of closo-dodecaborate in indirect labeling of antibodies for radioimmunoPET.

  • 8.
    Chajara, Khalil
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    Ottosson, Henrik
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    An improved pathway to 6,6-disubstituted fulvenes2004In: Tetrahedron Letters, no 45, p. 6741-6744Article in journal (Refereed)
    Abstract [en]

    Pentafulvenes with alkyl and/or aryl substituents at the exocyclic position are formed rapidly in high yields through reaction of crystalline sodium cyclopentadienide directly with the appropriate ketones.

  • 9.
    Cotton, Hanna
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Chiral metallocene ligands for transition metal-catalysed reactions2004Doctoral thesis, comprehensive summary (Other academic)
  • 10.
    Csjernyik, Gábor
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Studies of Biomimtic Oxidations and Racemizations2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis deals with studies of ruthenium-catalyzed hydrogen transfer reactions for oxidations and racemization.

    Through optimisation of the substrate-selective redox catalyst, the electron and proton transfer mediator (a benzoquinone derivative), and the oxygen-activating metal macrocycle a highly efficient biomimetic oxidation of secondary alcohols was obtained. Several alcohols were subjected to the new oxidation protocol and the corresponding ketones were isolated in high yield.

    The deactivation of the oxygen-activating metal macrocycle retarded the aerobic oxidation of primary alcohols. Encapsulation of the metal macrocycle into zeolite, described in chapter 3, proved to be an efficient method to solve this problem and comparable conversion of alcohols was achieved. The immobilization of the oxygen-activating porphyrin to a surface can be an alternative approach to solve the deactivation problem. Therefore as the first step towards studies of immobilized porphyrins on a metal surface (of gold or silver), S-thioacetyl derivatized porphyrins were synthesized; two alternative syntheses are described in chapter 4.

    A new and effecient ruthenium-catalyzed racemization protocol was established by proper ligand tuning. The racemization of the enantiomerically pure alcohols was increased significantly; this work is reported in chapter 5.

  • 11.
    Csjernyik, Gábor
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bogár, Krisztián
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    New Efficient Ruthenium Catalysts for Racemization of Alcohols at Room Temperature2004In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 45, no 36, p. 6799-6802Article in journal (Refereed)
    Abstract [en]

    5-Pentaphenylcyclopentadienyl)RuCl(CO)2 was found to catalyze efficiently the racemization of chiral alcohols such as (S)-1-phenylethanol, (S)-1-phenylpropan-2-ol, (S)-4-phenylbutan-2-ol and (S)-4-methoxy-1-phenylethanol at room temperature in the presence of a base. The catalytic activity of three other Ru(II) complexes was also investigated. The effects of halide and solvent were studied as well.

  • 12. Dybala-Defratyka, Agnieszka
    et al.
    Rostkowski, Michal
    Matsson, Olle
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    Westaway, Kenneth C.
    Paneth, Piotr
    A New Interpretation of Chlorine Leaving Group Kinetic Isotope Effects; A Theoretical Approach2004In: J. Org. Chem., Vol. 69, p. 4900-4905Article in journal (Refereed)
    Abstract [en]

    The chlorine leaving group kinetic isotope effects (KIEs) for the SN2 reactions between methyl chloride and a wide range of anionic, neutral, and radical anion nucleophiles were calculated in the gas phase and, in several cases, using a continuum solvent model. In contrast to the expected linear dependence of the chlorine KIEs on the Ca-CI bond order in the transition state, the KIEs fell in a very small range (1.0056-1.0091), even though the Ca-CI transition state bond orders varied widely from approximately 0.32 to 0.78, a range from reactant-like to very product-like. This renders chlorine KIEs, and possibly other leaving-group KIEs, less useful for studies of reaction mechanisms than commonly assumed. A partial explanation for this unexpected relationship between the Ca-CI transition state bond order and the magnitude of the chlorine KIE is presented.

  • 13.
    Edin, Michaela
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Córdova, Armando
    Tandem enantioselective organo- and biocatalysis: a direct entry for the synthesis of enantiomerically pure aldols2004In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 45, p. 7697-7701Article in journal (Refereed)
  • 14.
    Edin, Michaela
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Steinreiber, Johannes
    Bäckvall, Jan-E.
    One-pot synthesis of enantiopure syn-1,3-diacetates from racemic diastereomeric mixtures of 1,3-diols by dynamic kinetic asymmetric transformation2004In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, p. 5761-5766Article in journal (Refereed)
  • 15.
    Enander, Karin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    Dolphin, G. T.
    Baltzer, Lars
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    Designed functionalized helix-loop-helix motifs that bind human Carbonic Anhydrase II- a new class of synthetic receptor molecules2004In: J. Am. Chem. Soc., no 126, p. 4464-4465Article in journal (Refereed)
  • 16.
    Enander, Karin
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    Dolphin, G.T.
    Liedberg, B.
    Lundström, I.
    Baltzer, Lars
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    A versatile polypeptide platform for intergrated recognition and reporting - affinity arrays for protein - ligand interaction analysis2004In: Chem. Eur. J., no 10, p. 2375-2385Article in journal (Refereed)
  • 17. Enander, Karin
    et al.
    Dolphin, Gunnar T.
    Baltzer, Lars
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    Designed, functionalized helix-loop-helix motifs that bind human Carbonic Anhydrase II - a new class of synthetic receptor molecules2004In: J. Am. Chem. Soc., no 126, p. 4464-4465Article in journal (Refereed)
  • 18. Enander, Karin
    et al.
    Dolphin, Gunnar T.
    Liedberg, Bo
    Lundström, Ingemar
    Baltzer, Lars
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II.
    A versatile polypeptide platform for integrated recognition and reporting - affinity arrays for protein-ligand interaction2004In: Chem. Eur. J., no 10, p. 2375-2385Article in journal (Refereed)
  • 19.
    Engman, Lars
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Organisk kemi.
    Wojtón, A
    Oleksyn, B. J
    Sliwinski, J
    The crystal structure of 2-[N,N-dimethylamino)methyl] benzenetellurenyl chloride2004In: Phosphorus, Sulfur, and Silicon, ISSN 1042-6507, Vol. 179, p. 285-292Article in journal (Refereed)
    Abstract [en]

    The crystal structure of 2-[(N,N-dimethylamino)methyl]benzenetellurenyl chloride (2), a compound previously formulated as bis [[2-(N,N-dimethylamino)methyl]phenyl] ditelluride bis hydrochloride (1a), was determinded. In the molecule 2, tellurium is bonded to the carbon of the phenyl group [2.120(3)Å], the nitrogen o fthe ortho dimethylamino substituent [2.362(3)Å], and the chlorine atom [2.536[1]Å]. There also is an intermolecular interaction of the tellurium atom with the phenyl ring of a neighbouring molecule [3.655(1)Å], resulting in the formation of zigzag chains along the b axis. The noncentorsymmetric space group of the crystal can be explained by the chiral surrounding of tellurium.

  • 20.
    Engqvist, Robert
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institutet.
    Syntheses of some tri- and tetracyclic heterocycles containing an indole moiety2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis deals with the development of new synthetic methods leading to fused tri- and tetracyclic heterocycles, many of which have interesting biological activity such as antiviral and DNA intercalating properties. The reactions between isatins and 2-aminobenzylamine in acetic acid can give, depending on the conditions, either complex spirooxindoles or indolo[3,2-c]quinolin-6-ones. Proposed mechanisms are presented (involving a simpler form of spirooxindoles). These spirooxindoles can easily be obtained from isatins and 2-aminobenzylamine in methanol (Paper I). The previously unknown, but incorrectly claimed, linear isomer of indolo[3,2-c]quinolin-6one, i.e. indolo[2,3-b]quinolin-11-one, has been prepared for the first time by thermal (260 degrees C) cyclization of methyl 2 -phenylamino-indole-3 -carboxylate, which was in turn prepared in two steps from methyl indole-3 -carboxylate. The benzothiopyrano[2,3-b]indol-11-one and benzopyrano[2,3-b]indol-11-one could be prepared similarly (Papers I and II). Suitable 2-chloro-3-formylindoles have been used for the preparation of the alkaloids neocryptolepine, thienodolin and derivatives thereof (Papers III and IV). Finally, synthetic work towards potential metabolites of the lead compound B-220 is presented. We have described a method for reduction of the biologically interesting indolo[2,3b)quinoxalines with zinc, which are subsequently trapped with an appropriate anhydride to provide the corresponding mono or diacylated 5,1 1-dihydroindolo[2,3b]quinoxalines in good yields (paper V). Synthesis of hydroxy derivatives of B-220 can be effected from the appropriate methoxyisatins. Futher derivatives like the vinyl-, Nmethylaminoethyl- and Noxido derivatives of B-220 have also been synthesised.

  • 21.
    Engqvist, Robert
    et al.
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institutet.
    Bergman, Jan
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institutet.
    An improved synthesis of neocryptolepine2004In: Organic preparations and procedures international, ISSN 0030-4948, E-ISSN 1945-5453, Vol. 36, no 4, p. 386-390Article in journal (Refereed)
  • 22.
    Engqvist, Robert
    et al.
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institutet.
    Javaid, Atif
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science.
    Bergman, Jan
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institutet.
    Synthesis of thienodolin2004In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 12, p. 2589-2592Article in journal (Refereed)
    Abstract [en]

    We report a total synthesis of the alkaloid thienodolin (1a), as well as its 5-chloro isomer 1b and its unsubstituted analogue 1c, in three steps from the corresponding oxindoles Ba-c. The preparation was achieved through an initial Vilsmeier-Haack-Arnold reaction (chloro-formylation) followed by protection at the indole nitrogen, creation of the fused thiophene ring by nucleophilic substitution at the 2-position and an intramolecular cyclization using mercaptoacetamide. This gave 1a, 1b and 1c in total yields of 42%, 35% and 37%, respectively.

  • 23.
    Erdélyi, Máté
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Organic Chemistry.
    Towards the Development of Photoswitchable β-Hairpin Mimetics2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Peptide secondary structure mimetics are important tools in medicinal chemistry, as they provide analogues of endogeneous peptides with new physicochemical and pharmacological properties. The β-hairpin motif has been shown to be involved in numerous physiological processes, among others in regulation of eucariotic gene transcription. This thesis addresses the design, synthesis and conformational analysis of photoswitchable β-hairpin mimetics.

    The developmental work included the establishment of an improved procedure for cross coupling of aryl halides with terminal alkynes. Microwave mediated Sonogashira couplings in closed vessels were optimized under homogeneous and solid-phase conditions furnishing excellent yields for a large variety of substrates within 5 – 25 minutes. In addition, microwave heating was shown not to have any non-conventional effect on the reaction rate.

    Furthermore, the most important factors affecting β-hairpin stability were evaluated. Studies of tetrapeptide and decapeptide analogues revealed the essential role of the β-turn in initiation of hairpin folding. Moreover, hydrogen bonding was shown to be the main interchain stabilizing force, whereas hydrophobic interactions were found to be relatively weak. Nevertheless, hydrophobic packing appears to provide an important contribution to the thermodynamic stability of β-hairpins.

    Photoswitchable peptidomimetics were prepared by incorporation of various stilbene moieties into tetra- and decapeptides. Synthesis, photochemical isomerisation and spectroscopic conformational analysis of the compounds were performed.

  • 24.
    Ericsson, Cecilia
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Organic Chemistry.
    Synthesis of Tetrahydrofuran and Pyrrolidine Derivatives Utilising Radical Reactions: Organochalcogenides in Reductive, Carbonylative and Group-Transfer Cyclisation2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes free-radical reactions for the construction of tetrahydrofuran and pyrrolidine derivatives. The studies are concerned with (i) diastereoselectivity in radical cyclisation, (ii) construction of tetrahydrofuran-3-ones and pyrrolidin-3-ones via radical carbonylation/cyclisation and (iii) synthesis of tetrahydrofuran derivatives via group-transfer cyclisation of organochalcogen compounds.

    (i) Diastereoselectivity in the synthesis of tetrahydrofuran derivatives via radical cyclisation was controlled by addition of Lewis acids. In the synthesis of 2,4-disubstitued tetrahydrofurans, the trans-isomer was formed as the major product in the unperturbed reaction. Upon addition of trialkylalumiums the diastereoselectivity was reversed. In a similar fashion, exo/endo-diastereoselectivity in the synthesis of bicyclic 2,3,4-trisubstituted tetrahydrofurans could also be controlled.

    (ii) Procedures for construction of tetrahydrofuran-3-ones and pyrrolidin-3-ones were presented. Epoxides were ring-opened with benzeneselenolate or benzenetellurolate and the resulting β-hydroxyalkyl phenyl chalcogenides were vinylated using ethyl propiolate/NMM or E-1,2-bis(phenylsulfonyl)ethylene/NaH. The corresponding nitrogen analogues were accessed by N-vinylation of aziridines followed by benzeneselenolate ring-opening. The two types of organochalcogen radical precursors were then treated with TTMSS/AIBN under an atmosphere of carbon monoxide (80 atm) to afford tetrahydrofuran-3-ones and pyrrolidin-3-ones, respectively, in high yields.

    (iii) Microwaves were found to induce group-transfer cyclisation of β-allyloxyalkyl aryl chalcogenides. Short time heating (3-10 min) at 250 oC in ethylene glycol was required to obtain tetrahydrofuran derivatives in 60-91% yield.

  • 25.
    Ericsson, Cecilia
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Organisk kemi.
    Engman, Lars
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Microwave-Assisted Group-Transfer Cyclization of Organotellurium Compounds2004In: The Journal of Organic Chemistry, Vol. 69, no 15, p. 5143-5146Article in journal (Refereed)
    Abstract [en]

    Primary- and secondary-alkyl aryl tellurides, prepared by arenetellurolate ring-opening of epoxides/O-allylation, were, found to undergo rapid (3-10 min) group-transfer cyclization to afford tetrahydrofuran derivatives in 60-74% yield when heated in a microwave cavity at 250C in ethylene glycol or at 180C in water. To go to completion, similar transformations had previously required extended photolysis in refluxing benzene containing a substantial amount of hexabutylditin. The only drawback of the microwave-assisted process was the loss in diastereoselectivity wich is a consequence of the higher reaction temperature. Substitution in the Te-aryl moiety of the secondary-alkyl aryl tellurides (4-OMe, 4-H, 4-CF3) did not affect the outcome of the group-transfer reaction in ethylene glycol. However, at lower temperature, using water as a solvent, the CF3 derivative failed to react. The microwave-assisted grouptransfer cyclization was extended to benzylic but not to primary- and secondary-alkyl phenyl selenides.

  • 26. Forngren, Tobias
    et al.
    Samuelsson, Linda
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    Långström, Bengt
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    A 11C-methylstannane (5-[11C]methyl-1-aza-5-stannabicyclo[3.3.3] undecane) for use in palladium-mediated [11C]C-Cbond forming reactions with organic halides2004In: J. Labelled Compd. Rad., no 47, p. 71-78Article in journal (Refereed)
  • 27.
    Franzén, Johan
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium-Catalyzed Carbocyclizations of Allenes with Unsaturated Hydrocarbons2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Palladium-catalyzed reactions of unsaturated hydrocarbons are important processes in organic chemistry especially for the generation of ring systems. This thesis describes the development and mechanistic studies of carbocyclization reactions of allenes with olefins, allyls or 1,3-dienes catalyzed by palladium(0)- and palladium(II)-complexes. These reactions generally exhibit high stereo- and regioselectivity and give rise to stereodefined [n,3,0] bicyclic systems (n=3,4,5,6) in good to excellent yields. The mechanisms for these reactions were investigated with special attention directed to the intramolecular reaction of (π-allyl)palladium(II)-complexes and (π-1,3-diene)palladium(II)-complexes with allenes. It was demonstrated that the carbon-carbon bond formation occurred by nucleophilic attack of the middle carbon atom of the allene on the face of the allyl or 1,3-diene opposite to that of the palladium atom. Further, two new types of oxidative palladium(II)-catalyzed reactions between allenes and olefins or 1,3-dienes have been developed. These cyclizations constitute a new type of carbon-carbon bond forming reaction and there are support for a palladium(II)-catalyzed C-H activation at the allenic moiety rendering a vinylidienepalladium-intermediate followed by carbon-carbon bond formation via insertion of the olefin or 1,3-diene.

  • 28.
    Gabrielsson, Jon
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate methods in tablet formulation2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes the application of multivariate methods in a novel approach to the formulation of tablets for direct compression. It begins with a brief historical review, followed by a basic introduction to key aspects of tablet formulation and multivariate data analysis. The bulk of the thesis is concerned with the novel approach, in which excipients were characterised in terms of multiple physical or (in most cases) spectral variables. By applying Principal Component Analysis (PCA) the descriptive variables are summarized into a few latent variables, usually termed scores or principal properties (PP’s). In this way the number of descriptive variables is dramatically reduced and the excipients are described by orthogonal continuous variables. This means that the PP’s can be used as ordinary variables in a statistical experimental design. The combination of latent variables and experimental design is termed multivariate design or experimental design in PP’s. Using multivariate design many excipients can be included in screening experiments with relatively few experiments.

    The outcome of experiments designed to evaluate the effects of differences in excipient composition of formulations for direct compression is, of course, tablets with various properties. Once these properties, e.g. disintegration time and tensile strength, have been determined with standardised tests, quantitative relationships between descriptive variables and tablet properties can be established using Partial Least Squares Projections to Latent Structures (PLS) analysis. The obtained models can then be used for different purposes, depending on the objective of the research, such as evaluating the influence of the constituents of the formulation or optimisation of a certain tablet property.

    Several examples of applications of the described methods are presented. Except in the first study, in which the feasibility of this approach was first tested, the disintegration time of the tablets has been studied more carefully than other responses. Additional experiments have been performed in order to obtain a specific disintegration time. Studies of mixtures of excipients with the same primary function have also been performed to obtain certain PP’s. Such mixture experiments also provide a straightforward approach to additional experiments where an interesting area of the PP space can be studied in more detail. The robustness of a formulation with respect to normal batch-to-batch variability has also been studied.

    The presented approach to tablet formulation offers several interesting alternatives, for both planning and evaluating experiments.

  • 29. Garner, J.
    et al.
    Hill, T.
    Odell, L.R.
    Keller, P.
    Morgan, J.
    McCluskey, A.
    Identification of Aminopyrimidine Regioisomers via Line Broadening Effects in 1H and 13C NMR Spectroscopy2004In: Australian Journal of Chemistry, Vol. 57, no 11, p. 1079-1083Article in journal (Refereed)
    Abstract [en]

    Substituted mono- and diamino-pyrimidines were synthesized as part of our medicinal chemistry programmes. Primary amines substituted at the 4-position exhibited room-temperature line broadening effects in both 1H and 13C NMR spectroscopy due to the presence of rotamers, but these effects were not observed for substituents in the 2-position. This provided a simple diagnostic tool for the identification of regioisomers, a determination which would otherwise have required two-dimensional experiments.

  • 30.
    Gayet, Arnaud
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Organisk kemi.
    Bolea, Christine
    Andersson, Pher
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry I. Organisk kemi.
    Development of new camphor based N,S chiral ligands and their application in transfer hydrogenation2004In: Organic & Biomolecular Chemistry, no 2, p. 1887-1893Article in journal (Refereed)
  • 31.
    Ghirmai, Senait
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Synthesis of Organic Compounds for Nuclide Therapy: Derivatives of Carboranes, 9-Aminoacridine and Anthracyclines2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis addresses the synthesis of organic compounds, some of them are derivatives of compounds with DNA binding properties, for potential use in targeted nuclide therapy. The compounds synthesized therefore also need to contain potent nuclides. Here the nuclides considered are the radionuclide 125I, and the stable isotope 10B, which becomes radioactive upon neutron activation. 125I is an Auger-electron emitter, which emits particles that can travel only about 1-2 µm through human tissue and hence has to be delivered to the cancer cell nucleus to cause DNA damage. Neutron activated 10B emits highly cell killing α-particles and 7Li3+ ions, the application of which in Boron Nuclide Capture Therapy (BNCT) has proven very promising.

    The thesis can be divided into three parts:

    i) A nido-carborate, 7-(3´-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), has been synthesized and radioiodinated for use as a pendant group for attachment of 125I to tumor-seeking macromolecules. Radiolabeling was achieved in greater than 95% yield.

    ii) Both enantiomers of m-carboranylalanine, a carborane analogue of phenylalanine, have been prepared in high enantiomeric excess, and are of potential interest in BNCT. The synthesis involved amination of the N-acyl derivative formed from [3-(1,7-dicarba-closo-dodecarborane(12)-1-yl)-2-propanoic acid and Oppolzer’s camphor sultam.

    iii) Derivatives of the DNA intercalating compounds 9-aminoacridine, daunorubicin and doxorubicin have been synthesized and labeled with 125I. The 9-aminoacridines were synthesised with a variety of functional groups such as carboxyl, amino and hydroxyl. The anthracylines daunorubicin and doxorubicin are efficient chemotherapeutic agents; the synthesis routes of ester, amide and amine derivatives of these compounds are presented.

    The Chloramine T method was used for the radioiodinations, and the radioiodination precursors of both the acridine and the anthracycline derivatives, were made to contain either a trimethylstannyl group or a phenolic substituent. In the former case the trimethylstannyl group was replaced by 125I, and in the latter case, the compounds were radiolabeled directly at the o- position to the phenolic hydroxyl group. Both methods gave high radiolabeling yields.

  • 32.
    Ghirmai, Senait
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Malmquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Lundquist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Sjöberg, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Synthesis and Radioiodination of 7-(3´-Ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), (ANC)2004In: Journal of labelled compounds & radiopharmaceuticals, ISSN 0362-4803, E-ISSN 1099-1344, Vol. 47, no 9, p. 557-569Article in journal (Refereed)
    Abstract [en]

    Derivatives of nido-carborate have potential use in tumour targeting as hydrophilic boron-rich compounds for boron neutron capture therapy (BNCT) and as pendant groups for attachment of radiohalogens to tumour-seeking molecules. For this purpose, functionalized derivatives of nido-carborates that can be conjugated to biomolecules should be synthesized and evaluated. In this study, racemic 1, 7-(3′-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1) (acronym ANC) was obtained by degradation of the corresponding aminopropyl-o-carborane, which was synthesized in three steps from 1-tert-butyldimethylsilyl-2-(3-bromopropyl)-o-carborane, with sodium hydroxide in absolute ethanol. The racemate 1 was radioiodinated (125I) using the Chloramine-T method. Radio-TLC results showed that radiolabelling with 125I was achieved in a yield greater than 95%.

  • 33.
    Ghirmai, Senait
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Mume, Eskender
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Henssen, Cecile
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Ghaneolhusseini, Hadi
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Lundqvist, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Tolmachev, Vladimir
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Sjöberg, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry.
    Orlova, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences.
    Synthesis and Radioiodination of Some 9-Aminoacridine Derivatives2004In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 17, p. 3719-3725Article in journal (Refereed)
  • 34.
    Guliashvili, Tamaz
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry, Organic Chemistry.
    Synthesis and Reactivity Studies of Zwitterionic Silenes and 2-Silenolates2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes synthesis and reactivity studies of 2-amino-2-siloxysilenes and 2-silenolates, species that are strongly influenced by reversed Si=C bond polarization, i.e. an Siδ-=Cδ+ polarization as compared to the natural Siδ+=Cδ- polarization. Because of the reversed polarization, the 2-amino-2-siloxysilenes are zwitterions and the 2-silenolates are predominantly described by the resonance structure with the negative charge at Si.

    Transient zwitterionic 2-amino-2-siloxysilenes are formed thermolytically from carbamylpolysilanes (tris(trimethylsilyl)silylamides) and trapped with 1,3-dienes in nearly quantitative yields. These silenes have structure and reactivity characteristics that differ from earlier studied Si=C bonded compounds. They are thermodynamically stable toward dimerization and react with 1,3-dienes to give exclusively [4+2] cycloadducts. Their reactions with 1,3-dienes proceed in accordance with inverse electron demand (IED) Diels-Alder reactions which is explained by the electron-rich nature of these silenes. The 2-amino-2-siloxysilenes are also less reactive toward alcohols than earlier silenes. Hence, alcohols do not react with 2-amino-2-siloxysilenes but with the silene precursor, the carbamylpolysilanes, leading to alkoxysilanes in high yields. The latter reaction represents a novel base-free synthetic protocol for protection of primary and secondary alcohols with the fluoride resistant but photolabile tris(trimethylsilyl)silyl group.

    Another class of formally Si=C bonded compounds, metal 2-silenolates, has been formed in high yields using a novel facile method. Reaction of acyl- and carbamylpolysilanes with potassium tert-butoxide in tetrahydrofurane gives potassium 2-silenolates. The potassium 2-silenolates are stable at room temperature, in contrast to earlier lithium 2-silenolates that degrade rapidly at ambient temperature. The first crystallisable complex of a 2-silenolate was formed and characterized by X-ray crystallography. This 2-silenolate has a pyramidal central Si (ΣSi = 317.8°), and an Si-C single rather than Si=C double bond (r(SiC) = 1.926 Å). The potassium 2-silenolates give exclusively Si alkylated products with alkyl halides and only [4+2] cycloadducts with 1,3-dienes.

  • 35.
    Gustavsson, S
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
    Rosén, A
    Grennberg, H
    Bolton, K.
    Computational Studies of Carbon Nanotube-Hydrocarbon Bond Strengths at Nanotube Ends: Effect of Link Heteroatom and Hydrocarbon Structure2004In: Chemistry - A European Journal, Vol. 10, no 9, p. 2223-2227Article in journal (Refereed)
  • 36.
    Hallman, Kristina
    et al.
    KTH, Superseded Departments, Chemistry.
    Frölander, Anders
    KTH, Superseded Departments, Chemistry.
    Wondimagegn, Tebikie
    KTH, Superseded Departments, Chemistry.
    Svensson, Mats
    KTH, Superseded Departments, Chemistry.
    Moberg, Christina
    KTH, Superseded Departments, Chemistry.
    OH–Pd(0) Interaction as a Stabilizing Factor in Palladium-Catalyzed Allylic Alkylations2004In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, no 15, p. 5400-5404Article in journal (Refereed)
    Abstract [en]

    In palladium-catalyzed alkylations of allylic acetates with malonate as nucleophile, catalysts with oxazoline ligands bearing hydroxymethyl substituents in 4-position have been shown by density functional theory computations to undergo a conformational change on nucleophilic attack, which is accompanied by reduction of Pd(II) to Pd(0). The conformations of the Pd(0) complexes were shown to be governed by the presence of a hydrogen bond with the metal center acting as a hydrogen bond acceptor. The conformational change, which is absent in catalysts with O-alkylated analogs, largely affects the enantioselectivity of the catalytic process. This process is a previously uninvestigated example of where this type of weak hydrogen bond has been shown to influence the stereochemistry of a chemical reaction.

  • 37.
    Hedenström, Mattias
    Umeå University, Faculty of Science and Technology, Chemistry.
    NMR as a tool in drug research: Structure elucidation of peptidomimetics and pilicide-chaperone complexes2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In the last decades NMR spectroscopy has become an invaluable tool both in academic research and in the pharmaceutical industry. This thesis describes applications of NMR spectroscopy in biomedicinal research for structure elucidation of biologically active peptides and peptidomimetics as well as in studies of ligand-protein interactions.

    The first part of this thesis describes the theory and methodology of structure calculations of peptides using experimental restraints derived from NMR spectroscopy. This methodology has been applied to novel mimetics of the peptide hormones desmopressin and Leu-enkephalin. The results of these studies highlight the complicating issue of conformational exchange often encountered in structural determination of peptides and how careful analysis of experimental data as well as optimization of experimental conditions can enable structure determinations in such instances. Although the mimetics of both desmopressin and Leu-enkephalin were found to adopt the wanted conformations, they exhibited no or very poor biological activity. These results demonstrate the difficulties in designing peptidomimetics without detailed structural information of the receptors. A stereoselective synthetic route towards XxxΨ[CH2O]Ala pseudodipeptides is also presented. Such pseudodipeptides can be used as isosteric amide bond replacements in peptides in order to increase their resistance towards proteolytic degradation.

    The second part of this thesis describes the study of the interaction between compounds that inhibit pilius assembly, pilicides, and periplasmic chaperones from uropathogenic Escherichia coli. Periplasmic chaperones are key components in assembly of pili, i.e. hair-like protein complexes located on the surface of Escherichia coli that cause urinary tract infections. Detailed knowledge about this interaction is important in understanding how pilicides can inhibit pilus assembly by binding to chaperones. Relaxation-edited NMR experiments were used to confirm the affinity of the pilicides for the chaperones and chemical shift mapping was used to study the pilicide-chaperone interaction surface. These studies show that at least two interaction sites are present on the chaperone surface and consequently that two different mechanisms resulting in inhibition of pilus assembly may exist.

  • 38. Hederos, Sofia
    et al.
    Broo, Kerstin
    Jakobsson, Emma
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Biochemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Kleywegt, Gerard J
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Biochemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Mannervik, Bengt
    Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Biochemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    Baltzer, Lars
    Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Biochemistry. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Structural Molecular Biology.
    A new enzyme by rational design - the incorporation of a single His residue enables efficient thioester hydrolysis by human glutathione transferase A1-12004In: Proc. Nat. Acad. Sci., Vol. 101, p. 13163-13167Article in journal (Refereed)
    Abstract [en]

    A strategy for rational enzyme design is reported and illustrated by the engineering of a protein catalyst for thiol-ester hydrolysis. Five mutants of human glutathione (GSH; gamma-Glu-Cys-Gly) transferase A1-1 were designed in the search for a catalyst and to provide a set of proteins from which the reaction mechanism could be elucidated. The single mutant A216H catalyzed the hydrolysis of the S-benzoyl ester of GSH under turnover conditions with a k(cat)/K(M) of 156 M(-1) x min(-1), and a catalytic proficiency of >10(7) M(-1) when compared with the first-order rate constant of the uncatalyzed reaction. The wild-type enzyme did not hydrolyze the substrate, and thus, the introduction of a single histidine residue transformed the wild-type enzyme into a turnover system for thiol-ester hydrolysis. By kinetic analysis of single, double, and triple mutants, as well as from studies of reaction products, it was established that the enzyme A216H catalyzes the hydrolysis of the thiol-ester substrate by a mechanism that includes an acyl intermediate at the side chain of Y9. Kinetic measurements and the crystal structure of the A216H GSH complex provided compelling evidence that H216 acts as a general-base catalyst. The introduction of a single His residue into human GSH transferase A1-1 created an unprecedented enzymatic function, suggesting a strategy that may be of broad applicability in the design of new enzymes. The protein catalyst has the hallmarks of a native enzyme and is expected to catalyze various hydrolytic, as well as transesterification, reactions.

  • 39. Hill, Timothy A
    et al.
    Odell, Luke R
    Quan, Annie
    Abagyan, Ruben
    Ferguson, Gemma
    Robinson, Phillip J
    McCluskey, Adam
    Long chain amines and long chain ammonium salts as novel inhibitors of dynamin GTPase activity.2004In: Bioorganic & Medicinal Chemistry Letters, ISSN 0960-894X, E-ISSN 1090-2120, Vol. 14, no 12Article in journal (Refereed)
    Abstract [en]

    We examined a number of ligands with the view of inhibiting the GTPase activity of dynamin. Dynamin contains a pleckstrin homology (PH) domain that interacts with lipids. We report a series of simple lipid-like molecules that display moderate inhibitory activity. Inhibitory activity is linked to chain length and quaternarization of the terminal amine. A change in the counterion, Cl versus Br or I, had little effect on potency. However, introduction of a hydrophobic collar proximal to the charged site was beneficial to dynamin GTPase inhibitory action. The most potent compound was myristoyl trimethyl ammonium bromide (MTMAB, IC(50) 3.15 microM).

  • 40.
    Horváth, Attila
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mild and Efficient Palladium(II)-Catalyzed Racemization of Allenes2004In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, no 8, p. 964-965Article in journal (Refereed)
    Abstract [en]

    Allenes undergo racemization in the presence of catalytic amounts of Pd(OAc)2/LiBr under mild conditions; the reaction proceeds via a bromopalladation–debromopalladation sequence and tolerates various functional groups.

     

  • 41.
    Horváth, Attila
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-Erling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Benner, Jessica
    Simple, Enantiocontrolled Synthesis of 3-Pyrrolines from α-Amino Allenes2004In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, Vol. 2004, no 15, p. 3240-3243Article in journal (Refereed)
    Abstract [en]

    Cyclization of -amino allenes in the presence of N-bromosuccinimide afforded pyrrolines in good yields. The products were obtained with high enantiomeric excesses when optically active allenes were used as substrates. The synthesis of a 2,5-dehydroprolinol derivative is also presented.

  • 42.
    Ibrahem, Ismail
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Casas, Jesus
    Cordova, Armando
    Direct Catalytic Enantioselective a-aminomethylation of ketones2004In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 43, p. 6528-Article in journal (Refereed)
  • 43.
    Isaksson, Dan
    et al.
    KTH, Superseded Departments, Chemistry.
    Lindmark-Henriksson, Marcia
    KTH, Superseded Departments, Chemistry.
    Manoranjan, T
    Sjödin, Kristina
    KTH, Superseded Departments, Chemistry.
    Högberg, Hans-Erik
    KTH, Superseded Departments, Chemistry.
    Hemiacetals and their esters as side-products in lipase-catalysed transesterifications of vinyl esters with sterically hindered alcohols2004In: Journal of Molecular Catalysis B: Enzymatic, ISSN 1381-1177, E-ISSN 1873-3158, Vol. 31, p. 31-37Article in journal (Refereed)
    Abstract [en]

    Lipase-catalysed transesterifications of vinyl esters with various sterically hindered secondary alcohols sometimes give hemiacetals and hemiacetal esters as major side-products along with the expected esters, especially in the presence of aldehydes. The substrates, reaction conditions, and the lipases required for the formation of such hemiacetal products have been studied. Hemiacetals and their esters are very easily hydrolysed. Therefore, when conventional work-up procedures are used, the formation of such products in lipase-catalysed transesterification reactions may easily escape notice, leading to, e.g. an unexpectedly low enantiomeric purity of the isolated remaining substrate in a resolution reaction.

  • 44.
    Itsenko, Oleksiy
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    Kihlberg, Tor
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    Långström, Bengt
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry. Department of Biochemistry and Organic Chemistry, Organic Chemistry II. Organisk kemi.
    Photoinitiated Carbonylation with [11C]Carbon Monoxide Using Amines and Alkyl Iodides2004In: J. Org. Chem., no 69, p. 4356-4360Article in journal (Refereed)
  • 45.
    Johansson, Olof
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Wolpher, Henriette
    Borgström, Magnus
    Hammarström, Leif
    Bergquist, Jonas
    Sun, Licheng
    Åkermark, Björn
    Intramolecular charge separation in a hydrogen bonded tyrosune-ruthenium(II) baphthalene diimide triad2004In: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, p. 194-195Article in journal (Refereed)
  • 46.
    Johansson, Tommy
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Studies on Transformations of H-Phosphonates into DNA Analogues Containing P-S or P-C Bonds2004Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

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

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

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

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

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

  • 47.
    Johnson, Ann-Louise
    et al.
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institute.
    Bergman, Jan
    Södertörn University, School of Chemistry, Biology, Geography and Environmental Science. Karolinska Institute.
    Sjögren, M
    Bohlin, L
    Synthesis of barettin2004In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 60, no 4, p. 961-965Article in journal (Refereed)
    Abstract [en]

    The indole alkaloid barettin (with bromine in 6-position), isolated from the marine sponge Geodia Barretti, has been synthesised via a Horner-Wadsworth-Emmons type reaction from 6-bromoindole-3-carboxaldehyde to introduce the dehydro-functionality. Subsequent deprotection and cyclisation afforded the natural product in Z-conformation.

  • 48.
    Jönsson, Christina
    et al.
    KTH, Superseded Departments, Chemistry.
    Lundgren, Stina
    KTH, Superseded Departments, Chemistry.
    Haswell, S. J.
    Department of Chemistry, University of Hull.
    Moberg, Christina
    KTH, Superseded Departments, Chemistry.
    Asymmetric Catalysis in a Micro Reactor: Ce, Yb and Lu Catalysed Enantioselective Addition of Trimethylsilyl Cyanide to Benzaldehyde2004In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 60, no 46, p. 10515-10520Article in journal (Refereed)
    Abstract [en]

    A T-shaped micro reactor was used for the optimisation of reaction conditions for the enantioselective silyleyanation of benzaldehyde catalysed by lanthanide-pybox complexes. Compared to a conventional batch procedure, higher conversion was observed within shorter reaction time. The micro reactor process involving Lu(III) afforded essentially the same enantioselectivity as the batch process (73 vs 76% ee), whereas the enantioselectivity was lower in the micro reactor for catalysts containing Yb(III) (53 compared to 72%). Ce(III) provided very low selectivity in both types of processes (1 and 11 % ee, respectively). A study of the effect of additives showed that the enantioselectivity in the Yb catalysed reaction performed in the micro reactor could be increased to 66%, whereas only a minor improvement, to 78% ee, was observed in the reaction with Lu.

  • 49.
    Kjellgren, Johan
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sundén, Henrik
    Szabó, Kálmán J.
    Palladium Pincer-Complex Catalyzed Trimethyltin Substitution of Functionalized Propargylic Substrates: An Efficient Route to Propargyl- and Allenyl-Stannanes2004In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 126, no 2, p. 474-476Article in journal (Refereed)
  • 50.
    Källström, Klas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Hedberg, Christian
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Brandt, Peter
    Bayer, Annette
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Andersson, Pher
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry. Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Biochemistry and Organic Chemistry, Organic Chemistry I.
    Rationally Designed LIgands for Asymmetric Iridium-Catalyzed Hydrogenation of Olefins2004In: J. Am. Chem. Soc., no 126, p. 14308-14309Article in journal (Refereed)
    Abstract
123 1 - 50 of 110
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