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  • 51.
    Roth, Peter
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Asymmetric transfer hydrogenation of aromatic ketones and azirines with NH-ligands2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The Ru(arene)[(1S, 3R, 4R)-3-(Hydroxymethyl)-2-azabicyclo[2.2.1]heptane catalyst was optimized as ligand in the asymmetric transfer hydrogenation of ketones and resulted in increased activity and enantioselectivity of the catalyst. Dioxolane substitution at the rear end of the amino alcohol ligand and introduction of a (R)-methyl substituent yielded a catalyst that reduced acetophenone in 96% enantiomeric excess in 90 minutes with a substrate to catalyst molar ratio of 5000. A diversity of substituted aromatic ketones was reduced with excellent rate and enantioselectivity. Based on experimental and computational results, a study of the origin of the enantioselectivity was conducted. A combination of electrostatic, steric, dispersion forces and solvation effects was suggested to be the cause of the stereo discrimination. A set of amino sulfides built upon the 2-azabicyclo and the cyclohexane structures were prepared and tested as ligands in the enantioselective transfer hydrogenation of acetophenone with [IrCl(COD)]2 as metal precursor. With this type of catalysts, the reaction rates were good but the enantioselectivity unsatisfactory with 70% as the highest obtained enantiomeric excess. The first enantioselective reduction of aromatic 2H-azirines was accomplished by using the asymmetric transfer hydrogenation protocol. Aromatic azirines were reduced to yield chiral aziridines with up to 72% enantiomeric excess and good yields. The enantioselectivity and reactivity of the reaction were strongly influenced by substituents on the aromatic and aliphatic moiety of the substrate.

  • 52.
    Ryberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Concerted or Stepwise?: β-Elimination, Nucleophilic Substitution, Copper Catalysed Aziridination and Ruthenium Catalysed Transfer Hydrogenation Studied by Kinetic Isotope Effects and Linear Free-Energy Relationships2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis describes the use of kinetic isotope effects, linear free energy relationships and stereochamical studies to distinguish between different mechanistic alternatives and to obtain information about transition state structure.

    In the first part fluorine and deuterium kinetic isotope effects were determined for the base promoted HF elimination from 4-fluoro-4-(4’-nitrophenyl)butane-2-on. During this work a new method for the determination of fluorine kinetic isotope effects was developed. The results from the study demonstrates that the reaction proceeds via an E1cBip mechanism.

    In the second part the transition state structure for the SN2 reaction between ethyl chloride and cyanide ion in DMSO was studied. Kinetic isotope effects for six different positions in the reacting system, both in cyanide and ethyl chloride, were determined. The experimental isotope effects were then compared with the theoretically predicted isotope effects.

    The third part describes the use of Hammett type free-energy relationships and stereochemical evidence to study the mechanism of the copper catalysed alkene aziridination. The results from the study support a model that involves the simultaneous presence of two different copper nitrene intermediates. One which reacts non-stereospecifically via a radical intermediate and one which reacts stereospecifically via a concerted mechanism.

    In the fourth part a mechanistic study of the Ru(aminoalcohol) catalysed transfer hydrogenation of acetophenone in isopropanol is described. Kinetic isotope effects were determined for both proton and hydride transfer. The observation of significant primary deuterium kinetic isotope effects for both proton and hydride transfer support a mechanism where the proton and hydride are transferred simultaneously in a concerted mechanism.

  • 53.
    Schwartz, Lennart
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Eilers, Gerriet
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Fysikalisk kemi.
    Eriksson, Lars
    Gogoll, Adolf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Lomoth, Reiner
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Fysikalisk kemi.
    Ott, Sascha
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Fysikalisk kemi.
    Iron hydrogenase active site mimic holding a proton and a hydride2006Ingår i: Chemical Communications, ISSN 1359-7345, E-ISSN 1364-548X, Vol. 5, s. 520-522Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The first model of the iron hydrogenase active site has been prepared which concomitantly carries a proton and a hydride; the title species was characterized by IR and NMR spectroscopy and is reduced at more positive potential than any other mimic of this kind.

  • 54.
    Shanks, David
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Al-Maharik, Nawaf
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Malmström, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Engman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Eriksson, Petter
    Stenberg, Bengt
    Reitberger, Torbjörn
    Improved Antioxidant Formulations for Polymeric Materials: Synergistic Protective Effects in Combinations of Organotellurium Compounds with Conventional Phenolic Antioxidants or Thiols2003Ingår i: Polymer degradation and stability, ISSN 0141-3910, E-ISSN 1873-2321, Vol. 81, nr 2, s. 261-271Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    As judged by differential scanning calorimetry experiments at 190 °C and chemiluminescence measurements at 150 °C, addition of 0.10–0.30 wt.% of certain organotellurium compounds to polypropylene caused a notable protection against oxidation of the material. The best stabilizers (diaryl telluride 3 and alkyl aryl telluride 4), offered a similar degree of protection as commercial stabilizer formulations comprising a mixture of Irganox® 1010 and Irgafos® 168 (0.1 wt.% of each). The protective effect of the organotelluriums was substantially improved in combinations with sterically hindered phenols or thiols. The protection was often much better than the added effects of the individual components and, thus, can be considered as synergistic. Evaluation of a series of stabilizers where tellurium had been exchanged for selenium and sulfur (compounds 2) showed that the synergistic protective effect was unique for tellurium.

  • 55.
    Shanks, David
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Berlin, Stefan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Besev, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Ottosson, Henrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Engman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    On the origin of cis selectivity in the cyclization of N-protected 2-substituted 3-aza-5-hexenyl radicals: a density functional study2004Ingår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 69, nr 5, s. 1487-1491Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cyclization of the N-dimethylphosphinoyl-2-methyl-3-aza-5-hexenyl radical has been studied at the UB3LYP/6-31+G(d)//UB3LYP/6-31G(d) hybrid density functional level. The corresponding radical precursor has been synthesized and found to give cis/trans ratios of up to 10/1 in reductive radical cyclizations. The relative energies of reactant and transition state conformers were determined. In discord with the Beckwith-Houk model, it has been found that chair-axial transition states, which lead to cis products, are lowest in energy, rationalizing the observed experimental diastereoselectivity.

  • 56. Syvänen, Stina
    et al.
    Eriksson, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Genchel, Tove
    Lindhe, Örjan
    Antoni, Gunnar
    Långström, Bengt
    [1-11C]Ethyl iodide and [1-11C]propyl iodide in the synthesis of two potential NK1-receptor ligands and initial PET-imagingManuskript (Övrigt vetenskapligt)
  • 57.
    Trifonova, Anna
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Synthesis of Novel Chiral Bicyclic Ligands and their Application in Iridium-Catalyzed Reactions2005Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The synthesis of 2-aza-norborane derivatives is presented. The use of these compounds in preparation of Ir catalysts for asymmetric hydrogenations is described. The evaluation and optimization of the catalysts as well as the mechanistic aspects of the catalytic process are discussed.

    The use of non-activated iminodieniphiles in stereoselective aza-Diels-Alder reaction has expanded the scope of the reaction and provided a convenient root for preparation of 2-aza-norboranes, analogues of which were developed into novel bicyclic 2-aza-norbornyl-oxazoline ligands for Ir-catalyzed asymmetric transfer hydrogenations. Using ths Ir complexes acetophenone was hydrogenated in 79% ee.

    2-Aza-norbornyl-oxazolines were also developed into novel N,P-ligands. Resulting phosphine-oxazolines were evaluated in Ir-catalyzed asymmetric hydrogenation of structurally diverse imines and olefins.

    Optimization of ligands was performed through: 1) Alteration of the stereoconfiguration at the 5’-position as well as variation of the size and geometry of the substituents at this position; 2) Screening through various phosphine substituents of the ligand. Both directions of optimization reflect on the influence of the ligands’ sterik bulk on stereoselectivity of catalytic process. High performance catalysts were developed for both transformations allowing asymmetric hydrogenation of imines with 92% ee and asymmetric hydrogenation of olefins with 99% ee.

    Possible mechanisms for these transformations were suggested based on computational studies. Selectivity model for rationalization of results of Ir-catalyzed olefin hydrogenation also was designed.

    Delarbeten
    1. The use of nonactivated iminodienophiles in the stereoselective aza-Diels-Alder reaction
    Öppna denna publikation i ny flik eller fönster >>The use of nonactivated iminodienophiles in the stereoselective aza-Diels-Alder reaction
    2004 Ingår i: Tetrahedron: Asymmetry, ISSN 0957-4166, Vol. 15, nr 3, s. 445-452Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-93021 (URN)
    Tillgänglig från: 2005-05-04 Skapad: 2005-05-04Bibliografiskt granskad
    2. Development of a new class of (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-oxazoline ligands and their application in asymmetric transfer hydrogenation
    Öppna denna publikation i ny flik eller fönster >>Development of a new class of (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-oxazoline ligands and their application in asymmetric transfer hydrogenation
    2004 Ingår i: Tetrahedron, ISSN 0040-4020, Vol. 60, nr 15, s. 3393-3403Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-93022 (URN)
    Tillgänglig från: 2005-05-04 Skapad: 2005-05-04Bibliografiskt granskad
    3. Application of Phosphine-Oxazoline Ligands in Ir-Catalyzed Asymmetric Hydrogenation of Acyclic Aromatic N-Arylimines
    Öppna denna publikation i ny flik eller fönster >>Application of Phosphine-Oxazoline Ligands in Ir-Catalyzed Asymmetric Hydrogenation of Acyclic Aromatic N-Arylimines
    2004 Ingår i: Organic Letters, ISSN 1523-7060, Vol. 6, nr 21, s. 3825-3837Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-93023 (URN)
    Tillgänglig från: 2005-05-04 Skapad: 2005-05-04Bibliografiskt granskad
    4. Asymmetric Hydrogenation of Imines and Olefins Using Phosphine-oxazoline Iridium Complexes as Catalysts
    Öppna denna publikation i ny flik eller fönster >>Asymmetric Hydrogenation of Imines and Olefins Using Phosphine-oxazoline Iridium Complexes as Catalysts
    Manuskript (Övrigt vetenskapligt)
    Identifikatorer
    urn:nbn:se:uu:diva-93024 (URN)
    Tillgänglig från: 2005-05-04 Skapad: 2005-05-04 Senast uppdaterad: 2010-01-13Bibliografiskt granskad
  • 58.
    Trifonova, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Andersson, Pher G.
    The use of nonactivated iminodienophiles in the stereoselective aza-Diels-Alder reaction2004Ingår i: Tetrahedron: Asymmetry, ISSN 0957-4166, Vol. 15, nr 3, s. 445-452Artikel i tidskrift (Refereegranskat)
  • 59.
    Trifonova, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Andersson, Pher G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    The use of nonactivated iminodienophiles in the stereoselective aza-Diels-Alder reaction2004Ingår i: Tetrahedron: asymmetry, ISSN 0957-4166, E-ISSN 1362-511X, Vol. 15, nr 3, s. 445-452Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This paper describes the preparation of nitrogen-containing bicycles by the aza-Diels–Alderreaction ofnonactivatediminodienophiles and cyclopentadiene. Readily available starting materials such as (S)-(−)-lactate and l-amino acids were used for the preparation of chiral aldehydes with high enantiomeric excess. The improved oxidation procedure by Dess–Martin periodinane was employed for the synthesis of l-alanine derived phthalimide protected aldehyde 14, which was difficult to obtain in high enantiomeric excess by other methods. The influence of different Lewis acids on the stereoselectivity of the aza-Diels–Alderreactionwas also investigated: It was found that the use of a combination of BF3·Et2O and TFA in the cycloaddition leads to complete racemization of the imine prepared from 14 whereas the use of TiCl4 gives the cycloaddition products 17a and 17b with high enantioselectivity (90%).

  • 60.
    Trifonova, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Diesen, Jarle S.
    Andersson, Pher G.
    Asymmetric Hydrogenation of Imines and Olefins Using Phosphine-oxazoline Iridium Complexes as CatalystsManuskript (Övrigt vetenskapligt)
  • 61. Trifonova, Anna
    et al.
    Diesen, Jarle S.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Andersson, Pher G.
    Hydrogenation of Imines and Olefins Using Phosphine-Oxazoline Iridium Complexes as Catalysts2006Ingår i: Chemistry-A European Journal, Vol. 12, nr 8, s. 2318-2328Artikel i tidskrift (Refereegranskat)
  • 62. Trifonova, Anna
    et al.
    Diesen, Jarle S.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Chapman, Christopher C.
    Andersson, Pher G.
    Application of Phosphine-Oxazoline Ligands in Ir-Catalyzed Asymmetric Hydrogenation of Acyclic Aromatic N-Arylimines2004Ingår i: Organic Letters, Vol. 6, nr 21, s. 3825-3827Artikel i tidskrift (Refereegranskat)
  • 63.
    Trifonova, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Diesen, Jarle S.
    Chapman, Christopher J.
    Andersson, Pher G.
    Application of Phosphine-Oxazoline Ligands in Ir-Catalyzed Asymmetric Hydrogenation of Acyclic Aromatic N-Arylimines2004Ingår i: Organic Letters, ISSN 1523-7060, Vol. 6, nr 21, s. 3825-3837Artikel i tidskrift (Refereegranskat)
  • 64.
    Trifonova, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Diesen, Jarle S.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Chapman, Christopher J.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Andersson, Pher G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Application of Phosphine-Oxazoline Ligands in Ir-Catalyzed Asymmetric Hydrogenation of Acyclic Aromatic N-Arylimines2004Ingår i: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 6, nr 21, s. 3825-3827Artikel i tidskrift (Refereegranskat)
  • 65.
    Trifonova, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Källström, Klas E.
    Andersson, Pher G.
    Development of a new class of (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-oxazoline ligands and their application in asymmetric transfer hydrogenation2004Ingår i: Tetrahedron, ISSN 0040-4020, Vol. 60, nr 15, s. 3393-3403Artikel i tidskrift (Refereegranskat)
  • 66.
    Trifonova, Anna
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Källström, Klas E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Andersson, Pher G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Development of a new class of (1S,3R,4R)-2-azabicyclo[2.2.1]heptane-oxazoline ligands and their application in asymmetric transfer hydrogenation2004Ingår i: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 60, nr 15, s. 3393-3403Artikel i tidskrift (Refereegranskat)
  • 67.
    Velikyan, Irina
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Liljegren Sundberg, Åsa
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Lindhe, Örjan
    Höglund, A Urban
    Eriksson, Olof
    Werner, Eva
    Carlsson, Jörgen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Bergström, Mats
    Långström, Bengt
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Tolmachev, Vladimir
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för onkologi, radiologi och klinisk immunologi, Enheten för biomedicinsk strålningsvetenskap.
    Preparation and evaluation of (68)Ga-DOTA-hEGF for visualisation of EGFR expression in malignant tumours2005Ingår i: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 46, nr 11, s. 1881-1888Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Detection of epidermal growth factor receptor (EGFR) overexpression in many carcinomas provides important diagnostic information, which can influence patient management. The use of PET may enable such detection in vivo by a noninvasive procedure with high sensitivity. The aim of this study was to develop a method for preparation of a positron-emitting tracer based on a natural ligand to EGFR, the recombinant human epidermal growth factor (hEGF), and to perform a preclinical evaluation of the tracer.

    METHODS: DOTA-hEGF (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) was prepared by coupling of a N-sulfosuccinimide ester of DOTA to hEGF. The conjugate was labeled with a generator-produced positron-emitting nuclide, (68)Ga (half-life = 68 min), using microwave heating. Binding specificity, affinity, internalization, and retention of (68)Ga-DOTA-hEGF was studied in 2 EGFR-expressing cell lines, U343 glioma cells and A431 cervical carcinoma cells. Biodistribution and microPET visualization studies were performed in BALB/c nu/nu mice bearing A431 carcinoma xenografts.

    RESULTS: A 1-min-long microwave-assisted labeling provided radioactivity incorporation of 77% +/- 4%. Both cell lines demonstrated receptor-specific uptake of the conjugate, rapid internalization of the tracer, and good retention of radioactivity. Binding to both cell lines occurred with high affinity, approximately 2 nmol/L. The biodistribution study demonstrated accumulation of radioactivity in xenografts and in EGFR-expressing organs. The microPET imaging study enabled visualization of tumors and demonstrated quick--within 5 min--localization of radioactivity in tumors.

    CONCLUSION: (68)Ga-DOTA-hEGF has potential for imaging EGFR overexpression in tumors.

  • 68.
    Zeng, Xiaofeng
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Kemiska institutionen, Avdelningen för organisk kemi.
    Mechanisms for Solvolytic Elimination and Substitution Reactions Involving Short-lived Carbocation Intermediates2002Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Solvolysis reactions of a range of tertiary substrates in largely aqueous solvents were studied in such respects as β-deuterium kinetic isotope effects, linear free energy relationships and stereochemistry.

    Solvolysis of the fluorene derivatives 9-methyl–9-(2´-X-2´-propyl)fluorene (1-X, X = Cl, Br, OOCCF3) involves a very short-lived carbocation intermediate. The fraction of alkene is increased by addition of general bases, which can be expressed by a Brφnsted parameter β = 0.07. The kinetic deuterium isotope effects vary with solvent composition in a way which is not consistent with a common carbocation intermediate which has time to choose between dehydronation and addition of a solvent water molecule.

    In the absence of bases, the reaction of 4-chloro-4-(4´-nitrophenyl)pentan-2-one (2-Cl) proceeds through a short-lived carbocation intermediate yielding 4-(4´-nitrophenyl)-2-oxopent-4-ene (2-t-ne)as the main elimination product. Addition of acetate ion and other weak bases results in the base-promoted E2 (or E1cb) reaction to give (E)-4-(4´-nitrophenyl)-2-oxopent-3-ene (2-E-ne) and (Z)-4-(4´-nitrophenyl)-2-oxopent-3-ene(2-Z-ne). There is no evidence for a water-promoted E2 (or E1cb) reaction.

    The stereochemistry studies of elimination from (R,S and S,R)-[1-(3´-fluoro)phenyl-2-methyl]cyclopentyl-p-nitrobenzoate (3-PNB) and its (R,R and S,S)isomer 3´-PNB and (R,S and S,R)-[1´-(3´´-fluoro)phenyl-2´-methylcyclopentyl]-2,2,2-trifluoroacetate(3-OOCCF3) exclude the concerted pericyclic elimination mechanism for formation of the alkene 1-(3´-fluoro)phenyl-2-methylcyclopentene(3-m-ne). The effects of added thiocyanate ion and halide ions on the solvolysis reaction are discussed.

    Mass spectrometry analysis showed complete incorporation of the labeled oxygen from solvent water into the product 2-hydroxy-2-phenyl-3-butene (4-OH), confirming that it is the tertiary carbon-oxygen bond that is broken in the acid-catalyzed solvolysis of 2-methoxy-2-phenyl-3-butene (4-OMe). The mechanism for the dominant formation of the less stable 4-OH is discussed.

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