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  • 1. Afewerki, Samson
    et al.
    Ibrahem, Ismail
    Rydfjord, Jonas
    Breistein, Palle
    Córdova, Armando
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Direct Regiospecific and Highly Enantioselective Intermolecular α-Allylic Alkylation of Aldehydes by a Combination of Transition-Metal and Chiral Amine Catalysts2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 10, p. 2972-2977Article in journal (Refereed)
    Abstract [en]

    The first direct intermolecular regiospecific and highly enantioselective a-allylic alkylation of linear aldehydes by a combination of achiral bench-stable Pd0 complexes and simple chiral amines as co-catalysts is disclosed. The co-catalytic asymmetric chemoselective and regiospecific a-allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2-alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2-alkyl substituted hemiacetals, 2-alkyl-butane-1,4-diols, and amines. The concise co-catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.

  • 2.
    Ahlsten, Nanna
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bartoszewicz, Agnieszka
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Martín-Matute, Belén
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Allylic alcohols as synthetic enolate equivalents: Isomerisation and tandem reactions catalysed by transition metal complexes2012In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 41, no 6, p. 1660-1670Article in journal (Refereed)
    Abstract [en]

    Allylic alcohols can be isomerised into carbonyl compounds by transition metal complexes. In the last few years, catalyst design and development have resulted in highly efficient isomerisations under mild reaction conditions, including enantioselective versions. In addition, the isomerisation of allylic alcohols has been combined with C-C bond forming reactions when electrophiles such as aldehydes or imines were present in the reaction mixture. Also, C-F bonds can be formed when electrophilic fluorinating reagents are used. Thus, allylic alcohols can be treated as latent enol(ate)s. In this article, we highlight the latest developments concerning the isomerisation of allylic alcohols into carbonyl compounds, focusing in particular on tandem isomerisation/C-C or C-heteroatom bond formation processes. Significant attention is given to the mechanistic aspects of the reactions.

  • 3.
    Alam, Rauful
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pilarski, Lukasz T.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pershagen, Elias
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabo, Kalman J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Stereoselective intermolecular allylic C-H trifluoroacetoxylation of functionalized alkenes2012In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 21, p. 8778-8781Article in journal (Refereed)
    Abstract [en]

    Pd-catalyzed allylic C-H trifluoroacetoxylation of substituted alkenes was performed using PhI(OCOCF3)(2) as the oxidant and acyloxy source. Trifluoroacetoxylation of monosubstituted cyclopentenes and cyclohexenes proceeds with excellent regio- and diastereoselectivity. Studies with one of the possible (eta(3)-allyl)Pd(II) intermediates suggest that the reaction proceeds via stereoselective formation of Pd(IV) intermediates and subsequent stereo- and regioselective reductive elimination of the product.

  • 4. Barbion, Julien
    et al.
    Sorin, Geoffroy
    Selkti, Mohamed
    Kellenberger, Esther
    Baati, Rachid
    Santoro, Stefano
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pancrazi, Ange
    Lannou, Marie-Isabelle
    Ardisson, Janick
    Stereoselective functionalization of pyrrolidinone moiety towards the synthesis of salinosporamide A2012In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 68, no 32, p. 6504-6512Article in journal (Refereed)
    Abstract [en]

    An important feature of the synthesis of salinosporamide A. a potent proteasome inhibitor, is the establishment of the quaternary stereocenter at C3. A new route has been developed based on the methylation of a functionalized pyrrolidinone. Direct methylation reaction led to the unwanted diastereomer: however, by means of a Corey-Chaykovsky reaction followed by LiAlH4 epoxide opening, the desired alcohol was obtained. The pyrrolidinone was elaborated through a key allylation reaction between a tertiary allyltitanium reagent and an aldehyde bearing a spiroketal moiety in alpha-position.

  • 5.
    Bartoszewicz, Agnieszka
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Transition metal-catalysed hydrogen transfer processes for C-C and C-N bond formation: Synthetic studies and mechanistic investigations2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focusses on synthetic studies and mechanistic investigations into reactions involving hydrogen-transfer processes.

    In the first part, the development of an efficient method for the synthesis of β-hydroxy ketones (aldols) and β-amino ketones (Mannich products) from allylic alcohols and aldehydes is described. These reactions use  Ru(η5-C5Ph5)(CO)2Cl as the catalyst. The reaction parameters were optimised in order to suppress the formation of undesired by-products. Neutral and mild reaction conditions enabled the synthesis of a variety of aldol products in up to 99% yield, with a good syn/anti ratio. The influence of the stereoelectronic properties of the catalyst on the reaction outcome was also studied. Based on the results obtained, a plausible reaction mechanism has been proposed, involving as the key steps the 1,4-addition of hydride to α,β-unsaturated ketones and the formation of ruthenium (Z)-enolates.

    In the second part of this thesis, a ruthenium-catalysed tandem isomerisation/C-H activation reaction is presented. A number of ruthenium complexes, phosphine ligands, and additives were evaluated in order to establish the optimal reaction conditions. It was found that the use of a stable ruthenium catalyst, Ru(PPh3)3Cl2, together with PtBu3 and HCO2Na resulted in an efficient tandem transformation. Using this procedure, a variety of ortho-alkylated ketones were obtained in excellent yields. Moreover, homoallylic alcohols could also be used as starting materials for the reaction, which further expands the substrate scope. Mechanistic investigations into the isomerisation part of the process were carried out.

    The last project described in the thesis deals with the design and preparation of novel bifunctional iridium complexes containing an N-(2-hydroxy-isobutyl)-N-Heterocyclic carbene ligand. These complexes were used as catalysts to alkylate amines using alcohols as latent electrophiles. The catalytic system developed here was found to be one of the most active systems reported to date, allowing the reaction to be performed at temperatures as low as 50 °C for the first time. A broad substrate scope was examined. Combined experimental and theoretical studies into the reaction mechanism are consistent with a metal-ligand bifunctional activity of the new catalyst.

  • 6.
    Bartoszewicz, Agnieszka
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Jezowska, Martina M.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Laymand, Kevin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Mobus, Juri
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Martín-Matute, Belén
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of β-Hydroxy and β-Amino Ketones from Allylic Alcohols Catalyzed by Ru(η5-C5Ph5)(CO)2Cl2012In: European Journal of Inorganic Chemistry, ISSN 1434-1948, E-ISSN 1099-1948, no 9, p. 1517-1530Article in journal (Refereed)
    Abstract [en]

    An efficient method for the synthesis of beta-hydroxy and beta-amino ketones from allylic alcohols catalyzed by Ru(5-C5Ph5)(CO)2Cl is described. The influence of the stereoelectronic properties of the catalyst on the reaction outcome has been studied. Optimization of the reaction conditions supressed the formation of undesired side products such as saturated ketones, benzyl alcohols, and a,beta-unsaturated ketones. Several aromatic and aliphatic allylic alcohols have been reacted with a large variety of aldehydes or imines to produce beta-hydroxy ketones or beta-amino ketones, respectively, in yields up to 99%. Based on experimental data, a mechanism via ruthenium alkoxides and ruthenium aldoxides is proposed. In addition, a C-bound ruthenium enolate has been characterized.

  • 7.
    Bartoszewicz, Agnieszka
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Marcos, Rocio
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sahoo, Suman
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Inge, A. Ken
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Zou, Xiaodong
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Martín-Matute, Belén
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    A Highly Active Bifunctional Iridium Complex with an Alcohol/Alkoxide-Tethered N-Heterocyclic Carbene for Alkylation of Amines with Alcohols2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 45, p. 14510-14519Article, review/survey (Refereed)
    Abstract [en]

    A series of new iridium(III) complexes containing bidentate N-heterocyclic carbenes (NHC) functionalized with an alcohol or ether group (NHC?OR, R=H, Me) were prepared. The complexes catalyzed the alkylation of anilines with alcohols as latent electrophiles. In particular, biscationic IrIII complexes of the type [Cp*(NHC-OH)Ir(MeCN)]2+2[BF4-] afforded higher-order amine products with very high efficiency; up to >99?% yield using a 1:1 ratio of reactants and 12.5 mol?% of Ir, in short reaction times (216 h) and under base-free conditions. Quantitative yields were also obtained at 50?degrees C, although longer reaction times (4860 h) were needed. A large variety of aromatic amines have been alkylated with primary and secondary alcohols. The reactivity of structurally related iridium(III) complexes was also compared to obtain insights into the mechanism and into the structure of possible catalytic intermediates. The IrIII complexes were stable towards oxygen and moisture, and were characterized by NMR, HRMS, single-crystal X-ray diffraction, and elemental analyses.

  • 8. Barzegar, Hamid Reza
    et al.
    Nitze, Florian
    Malolepszy, Artur
    Stobinski, Leszek
    Tai, Cheuk-Wai
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Wagberg, Thomas
    Water Assisted Growth of C-60 Rods and Tubes by Liquid-Liquid Interfacial Precipitation Method2012In: Molecules, ISSN 1420-3049, E-ISSN 1420-3049, Vol. 17, no 6, p. 6840-6853Article in journal (Refereed)
    Abstract [en]

    C-60 nanorods with hexagonal cross sections are grown using a static liquid-liquid interfacial precipitation method in a system of C-60/m-dichlorobenzene solution and ethanol. Adding water to the ethanol phase leads instead to C-60 tubes where both length and diameter of the C-60 tubes can be controlled by the water content in the ethanol. Based on our observations we find that the diameter of the rods/tubes strongly depends on the nucleation step. We propose a liquid-liquid interface growth model of C-60 rods and tubes based on the diffusion rate of the good C-60 containing solvent into the poor solvent as well as on the size of the crystal seeds formed at the interface between the two solvents. The grown rods and tubes exhibit a hexagonal solvate crystal structure with m-dichlorobenzene solvent molecules incorporated into the crystal structure, independent of the water content. An annealing step at 200 degrees C at a pressure <1 kPa transforms the grown structures into a solvent-free face centered cubic structure. Both the hexagonal and the face centered cubic structures are very stable and neither morphology nor structure shows any signs of degradation after three months of storage.

  • 9.
    Bouma, Marinus J.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    General One-Pot Synthesis of Alkynyliodonium Salts and Alkynyl Benziodoxolones from Aryl Iodides2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 45, p. 14242-14245Article in journal (Refereed)
  • 10.
    Buitrago, Elina
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Transition metal-catalyzed reduction of carbonyl compounds: Fe, Ru and Rh complexes as powerful hydride mediators2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A detailed mechanistic investigation of the previously reported ruthenium pseudo-dipeptide-catalyzed asymmetric transfer hydrogenation (ATH) of aromatic ketones was performed. It was found that the addition of alkali metals has a large influence on both the reaction rate and the selectivity, and that the rate of the reaction was substantially increased when THF was used as a co-solvent. A novel bimetallic mechanism for the ruthenium pseudo-dipeptide-catalyzed asymmetric reduction of prochiral ketones was proposed.

    There is a demand for a larger substrate scope in the ATH reaction, and heteroaromatic ketones are traditionally more challenging substrates. Normally a catalyst is developed for one benchmark substrate, and a substrate screen is carried out with the best performing catalyst. There is a high probability that for different substrates, another catalyst could outperform the one used. To circumvent this issue, a multiple screen was executed, employing a variety of ligands from different families within our group’s ligand library, and different heteroaromatic ketones to fine-tune and to find the optimum catalyst depending on the substrate. The acquired information was used in the formal total syntheses of (R)-fluoxetine and (S)-duloxetine, where the key reduction step was performed with high enantioselectivities and high yield, in each case.

    Furthermore, a new iron-N-heterocyclic carbene (NHC)-catalyzed hydrosilylation (HS) protocol was developed. An active catalyst was formed in situ from readily available imidazolium salts together with an iron source, and the inexpensive and benign polymethylhydrosiloxane (PMHS) was used as hydride donor. A set of sterically less demanding, potentially bidentate NHC precursors was prepared. The effect proved to be remarkable, and an unprecedented activity was observed when combining them with iron. The same system was also explored in the reduction of amides to amines with satisfactory results.

  • 11.
    Buitrago, Elina
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lundberg, Helena
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Andersson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ryberg, Per
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    High Throughput Screening of a Catalyst Library for the Asymmetric Transfer Hydrogenation of Heteroaromatic Ketones: Formal Syntheses of (R)-Fluoxetine and (S)-Duloxetine2012In: ChemCatChem, ISSN 1867-3880, E-ISSN 1867-3899, Vol. 4, no 12, p. 2082-2089Article in journal (Refereed)
    Abstract [en]

    A total of 21 amino acid based ligands including hydroxy amide, thioamide, and hydroxamic acid functionalities, respectively, were combined with [Ru(p-cymene)Cl2]2 and [RhCp*Cl2]2, and used as catalysts for the asymmetric transfer hydrogenation of four different heteroaromatic ketones in 2-propanol. The reactions were performed on a Chemspeed automated high-throughput screening robotic platform. Optimal catalysts were identified for the individual heterocyclic substrate classes. Based on these results, the formal syntheses of the antidepressant drugs (R)-fluoxetine and (S)-duloxetine were conducted by using the found catalysts in the key reaction step, which results in high isolated yields (94?%) and excellent product enantioselectivities (>99?% ee) of the formed 1,3-amino alcohols.

  • 12.
    Buitrago, Elina
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Tinnis, Fredrik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Efficient and Selective Hydrosilylation of Carbonyls Catalyzed by Iron Acetate and N-Hydroxyethylimidazolium Salts2012In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 354, no 1, p. 217-222Article in journal (Refereed)
    Abstract [en]

    Aromatic aldehydes, along with aryl alkyl, heteroaryl alkyl, and dialkyl ketones were efficiently reduced to their corresponding primary and secondary alcohols, respectively, in high yields, using the commercially available and inexpensive polymeric silane, polymethylhydrosiloxane (PMHS), as reducing agent. The reaction is catalyzed by in situ generated iron complexes containing hydroxyethyl-functionalized NHC ligands. Turnover frequencies up to 600 h−1 were obtained

  • 13. Coll, Mercedes
    et al.
    Ahlford, Katrin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pamies, Oscar
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Dieguez, Montserrat
    Modular Furanoside Pseudodipeptides and Thioamides, Readily Available Ligand Libraries for Metal-Catalyzed Transfer Hydrogenation Reactions: Scope and Limitations2012In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 354, no 2-3, p. 415-427Article in journal (Refereed)
    Abstract [en]

    Two new highly modular carbohydrate-based, pseudodipeptide and thioamide ligand libraries have been synthesized for the rhodium- and ruthenium-catalyzed asymmetric transfer hydrogenation (ATH) of prochiral ketones. These series of ligands can be prepared efficiently from easily accessible D-xylose and D-glucose. The ligand libraries contain two main ligand structures (pseudodipeptide and thioamide) that have been designed by making systematic modifications to one of the most successful ligand families developed for the ATH. As well as studying the effect of these two ligand structures on the catalytic performance, we also evaluated the effect of modifying several of the ligand parameters. We found that the effectiveness of the ligands at transferring the chiral information in the product can be tuned by correctly choosing the ligand components (ligand structure and ligand parameters). Excellent enantioselectivities (ees up to 99%) were therefore obtained in both enantiomers of the alcohol products using a wide range of substrates.

  • 14.
    Deiana, Luca
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Afewerki, Samson
    Palo-Nieto, Carlos
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Verho, Oscar
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Johnston, Eric V.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cordova, Armando
    Stockholm University, Faculty of Science, Department of Organic Chemistry. Mid Sweden University.
    Highly Enantioselective Cascade Transformations by Merging Heterogeneous Transition Metal Catalysis with Asymmetric Aminocatalysis2012In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 2, p. 851-Article in journal (Refereed)
    Abstract [en]

    The concept of combining heterogeneous transition metal and amine catalysis for enantioselective cascade reactions has not yet been realized. This is of great advantage since it would allow for the recycling of expensive and non-environmentally friendly transition metals. We disclose that the use of a heterogeneous Pd-catalyst in combination with a simple chiral amine co-catalyst allows for highly enantioselective cascade transformations. The preparative power of this process has been demonstrated in the context of asymmetric cascade Michael/carbocyclization transformations that delivers cyclopentenes bearing an all carbon quaternary stereocenters in high yields with up to 30: 1 dr and 99% ee. Moreover, a variety of highly enantioselective cascade hetero-Michael/carbocyclizations were developed for the one-pot synthesis of valuable dihydrofurans and pyrrolidines (up to 98% ee) by using bench-stable heterogeneous Pd and chiral amines as co-catalysts.

  • 15.
    Deiana, Luca
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Zhao, Gui-Ling
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Leijonmarck, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lehmann, Christian
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Physical, Inorganic and Structural Chemistry, Structural Chemistry.
    Lehmann, Christian W.
    Córdova, Armando
    Stockholm University, Faculty of Science, Department of Organic Chemistry. Mid Sweden University.
    Direct Catalytic Asymmetric Synthesis of Pyrazolidine Derivatives2012In: ChemistryOpen, ISSN 2191-1363, Vol. 1, no 3, p. 134-139Article in journal (Refereed)
    Abstract [en]

    A highly enantioselective, metal-free cascade reaction between di-1,2-N-protected hydrazine and α,β-unsaturated aldehydes is disclosed. The catalytic, asymmetric cascade transformation is a direct entry to 3-hydroxypyrazolidine and 3-allylpyrazolidine derivatives in one step and two steps, respectively, with >19:1 d.r. and 98–99 % ee using simple chiral pyrrolidines as catalysts.

  • 16.
    Deng, Youqian
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bartholomeyzik, Teresa
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Persson, Andreas K. A.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Sun, Junliang
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium-Catalyzed Oxidative Arylating Carbocyclization of Allenynes2012In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 51, no 11, p. 2703-2707Article in journal (Refereed)
  • 17.
    Engström, Karin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Enantioselective biotransformations using engineered lipases from Candida antarctica2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Enzymes are attractive catalysts in organic synthesis since they are efficient, selective and environmentally friendly. A large number of enzyme-catalyzed transformations have been described in the literature. If no natural enzyme can carry out a desirable reaction, one possibility is to modify an existing enzyme by protein engineering and thereby obtain a catalyst with the desired properties. In this thesis, the development of enantioselective enzymes and their use in synthetic applications is described. 

    In the first part of this thesis, enantioselective variants of Candida antarctica lipase A (CALA) towards α-substituted p-nitrophenyl esters were developed by directed evolution. A highly selective variant of CALA towards p-nitrophenyl 2-phenylpropanoate was developed by pairwise randomization of amino acid residues close to the active site. The E value of this variant was 276 compared to 3 for the wild type.

    An approach where nine residues were altered simultaneously was used to discover another highly enantioselective CALA variant (E = 100) towards an ibuprofen ester. The sterical demands of this substrate made it necessary to vary several residues at the same time in order to reach a variant with improved properties.

    In the second part of the thesis, a designed variant of Candida antarctica lipase B (CALB) was employed in kinetic resolution (KR) and dynamic kinetic resolution (DKR) of secondary alcohols. The designed CALB variant (W104A) accepts larger substrates compared to the wild type, and by the application of CALB W104A, the scope of these resolutions was extended.

    First, a DKR of phenylalkanols was developed using CALB W104A. An enzymatic resolution was combined with in situ racemization of the substrate, to yield the products in up to 97% ee. Secondly, the KR of diarylmethanols with CALB W104A was developed. By the use of diarylmethanols with two different aryl groups, highly enantioselective transformations were achieved.

  • 18.
    Engström, Karin
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Vallin, Michaela
    Hult, Karl
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kinetic resolution of diarylmethanols using a mutated variant of lipase CALB2012In: Tetrahedron, ISSN 0040-4020, E-ISSN 1464-5416, Vol. 68, no 37, p. 7613-7618Article in journal (Refereed)
    Abstract [en]

    An enzymatic kinetic resolution of diarylmethanols via acylation has been developed. This was achieved by the use of a mutated variant of CALB that accepts larger substrates compared to the wild type. By the use of diarylmethanols with two differently sized aryl groups, enantioselective transformations were achieved. A larger size-difference led to a higher enantioselectivity. In addition, substrates with electronically different aryl groups, such as phenyl and pyridyl, also gave an enantioselective reaction. The highest E value was observed with a substrate where steric and electronic effects were combined.

  • 19.
    Eriksson, Lars
    et al.
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Methyl 3-O-α-l-fucopyranosyl β-d-glucopyranoside tetrahydrate2012In: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. 68, p. o3180-o3181Article in journal (Refereed)
    Abstract [en]

    The title compound, C13H24O10·4H2O, is the methyl glycoside of a disaccharide structural element present in the backbone of the capsular polysaccharide from Klebsiella K1, which contains only three sugars and a substituent in the polysaccharide repeating unit. The conformation of the title disaccharide is described by the glycosidic torsion angles ϕH = 51.1 (1)° and ψH = 25.8 (1)°. In the crystal, a number of O—HO hydrogen bonds link the methyl glycoside and water mol­ecules, forming a three-dimensional network. One water mol­ecule is disordered over two positions with occupancies of 0.748 (4) and 0.252 (4).

  • 20. Eriksson, Lars
    et al.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Methyl α-l-rhamnosyl-(1→2)[α-l-rhamnosyl-(1→3)]-α-l-rhamnoside penta­hydrate: synchrotron study2012In: Acta Crystallographica Section E: Structure Reports Online, ISSN 1600-5368, E-ISSN 1600-5368, Vol. 68, no 7, p. o2221-o2222Article in journal (Refereed)
    Abstract [en]

    The title hydrate, C19H34O13·5H2O, contains a vicinally disubstituted tris­accharide in which the two terminal rhamnosyl sugar groups are positioned adjacent to each other. The conformation of the tris­accharide is described by the glycosidic torsion angles ϕ2 = 48 (1)°, ψ2 = −29 (1)°, ϕ3 = 44 (1)° and ψ3 = 4 (1)°, whereas the ψ2 torsion angle represents a conformation from the major state in solution, the ψ3 torsion angle conformation may have been caught near a potential energy saddle-point when compared to its solution structure, in which at least two but probably three conformational states are populated. Extensive inter­molecular O—HO hydrogen bonding is present in the crystal and a water-containing channel is formed along the b-axis direction.

  • 21.
    Fontana, Carolina
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Structural studies of glycans by NMR spectroscopy2012Licentiate thesis, comprehensive summary (Other academic)
  • 22.
    Fontana, Carolina
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Lundborg, Magnus
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Weintraub, Andrej
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Structural studies and biosynthetic aspects of the o antigen polysaccharide from Escherichia coli o1742012In: Carbohydrate Research, ISSN 0008-6215, E-ISSN 1873-426X, Vol. 354, p. 102-105Article in journal (Refereed)
    Abstract [en]

    The structure of the repeating unit of the O-antigenic polysaccharide (PS) from Escherichia coli O174 has been determined. Component analysis together with H-1 and C-13 NMR spectroscopy experiments were employed to elucidate the structure. Inter-residue correlations were determined by H-1, C-13-heteronuclear multiple-bond correlation and H-1, H-1-NOESY experiments. The PS is composed of tetrasaccharide repeating units with the following structure: -> 4)-beta-D-GlcpA-(1 -> 3)-beta-D-Galp-(1 -> 3)-beta-D-GalpNAc-(1 -> vertical bar beta-D-GlcpNAc-(1 -> 2) Cross-peaks of low intensity were present in the NMR spectra consistent with a beta-D-GlcpNAc-(1 -> 2)-beta-D-GlcpA(1 -> structural element at the terminal part of the polysaccharide, which on average is composed of similar to 15 repeating units. Consequently the biological repeating unit has a 3-substituted N-acetyl-D-galactosamine residue at its reducing end.

  • 23.
    Jalalian, Nazli
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development and Applications of Hypervalent Iodine Compounds: Powerful Arylation and Oxidation Reagents2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The first part of this thesis describes the efficient synthesis of several hypervalent iodine(III) compounds. Electron-rich diaryliodonium salts have been synthesized in a one-pot procedure, employing mCPBA as the oxidant. Both symmetric and unsymmetric diaryliodonium tosylates can be isolated in high yields. An in situ anion exchange also enables the synthesis of previously unobtainable diaryliodonium triflates.

    A large-scale protocol for the synthesis of a derivative of Koser’s reagent, that is an isolable intermediate in the diaryliodonium tosylate synthesis, is furthermore described. The large-scale synthesis is performed in neat TFE, which can be recovered and recycled. This is very desirable from an environmental point of view.

    One of the few described syntheses of enantiopure diaryliodonium salts is discussed. Three different enantiopure diaryliodonium salts bearing electron-rich substituents are synthesized in moderate to high yields. The synthesis of these three salts shows the challenge in the preparation of electron-rich substituted unsymmetric salts.

    The second part of the thesis describes the application of both symmetric and unsymmetric diaryliodonium salts in organic synthesis. A metal-free efficient and fast method for the synthesis of diaryl ethers from diaryliodonium salts has been developed. The substrate scope is wide as both the phenol and the diaryliodonium salt can be varied. Products such as halogenated ethers, ortho-substituted ethers and bulky ethers, that are difficult to obtain with metal-catalyzed procedures, are readily prepared. The mild protocol allows arylation of racemization-prone a-amino acid derivatives without loss of enantiomeric excess.

    A chemoselectivity investigation was conducted, in which unsymmetric diaryliodonium salts were employed in the arylation of three different nucleophiles in order to understand the different factors that influence which aryl moiety that is transferred to the nucleophile.

  • 24.
    Jalalian, Nazli
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Petersen, Tue B.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Olofsson, Berit
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Metal-Free Arylation of Oxygen Nucleophiles with Diaryliodonium Salts2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 44, p. 14140-14149Article in journal (Refereed)
    Abstract [en]

    Phenols and carboxylic acids are efficiently arylated with diaryliodonium salts. The reaction conditions are mild, metal free, and avoid the use of halogenated solvents, additives, and excess reagents. The products are obtained in good-to-excellent yields after short reaction times. Steric hindrance is very well tolerated, both in the nucleophile and diaryliodonium salt. The scope includes ortho-and halo-substituted products, which are difficult to obtain by metal-catalyzed protocols. Many functional groups are tolerated, including carbonyl groups, heteroatoms, and alkenes. Unsymmetric salts can be chemoselectively utilized to obtain products with hitherto unreported levels of steric congestion. The arylation has been extended to sulfonic acids, which can be converted to sulfonate esters by two different approaches. With recent advances in efficient synthetic procedures for diaryliodonium salts the reagents are now inexpensive and readily available. The iodoarene byproduct formed from the iodonium reagent can be recovered quantitatively and used to regenerate the diaryliodonium salt, which improves the atom economy.

  • 25.
    Janson, Pär G.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Metal-catalyzed oxidative formation of C-CF3 and C-O bonds in alkenes and alkynes2012Licentiate thesis, comprehensive summary (Other academic)
  • 26.
    Janson, Pär G.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ghoneim, Ibrahim
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ilchenko, Nadia O.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabó, Kálmán J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Electrophilic Trifluoromethylation by Copper-Catalyzed Addition of CF3-Transfer Reagents to Alkenes and Alkynes2012In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 14, no 11, p. 2882-2885Article in journal (Refereed)
    Abstract [en]

    Regio- and stereoselective Cu-catalyzed addition of the above hypervalent iodine reagent to alkynes and alkenes was achieved. In the presence of Cul, the reaction is suitable to perform trifluoromethyl-benzoyloxylation and trifluoromethyl-halogenation of alkenes and alkynes. Electron-donating substituents accelerate the process, and alkenes react faster than alkynes emphasizing the electrophilic character of the addition reaction.

  • 27.
    Jiang, Min
    et al.
    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.
    Palladium-Catalyzed Oxidative Diarylating Carbocyclization of Enynes2012In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 14, no 13, p. 3538-3541Article in journal (Refereed)
    Abstract [en]

    A mild and efficient palladium-catalyzed oxidative diarylating carbocyclization of enynes is described. The reaction tolerates a range of functionalized arylboronic acids to give diarylated products in good yields. Control experiments suggest that the reaction starts with an arylpalladation of the alkyne, followed by carbocyclization, transmetalation, and reductive elimination to afford the diarylated product.

  • 28.
    Jiang, Tuo
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium(II)-catalyzed oxidativecarbocyclization: Functionalization with Boron-Containing Reagents2012Licentiate thesis, comprehensive summary (Other academic)
  • 29.
    Johnston, Eric V.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Verho, Oscar
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kärkäs, Markus
    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).
    Palmgren, Pål
    Eriksson, Kristofer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Oscarsson, Sven
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Highly dispersed palladium nanoparticles on mesocellular foam: an efficient and recyclable heterogeneous catalyst for alcohol oxidation2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 39, p. 12202-12206Article in journal (Refereed)
  • 30.
    Jonsson, K. Hanna M.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Säwén, Elin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Studies on the conformational flexibility of alpha-L-rhamnose-containing oligosaccharides using C-13-site-specific labeling, NMR spectroscopy and molecular simulations: implications for the three-dimensional structure of bacterial rhamnan polysaccharides2012In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 10, no 12, p. 2453-2463Article in journal (Refereed)
    Abstract [en]

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

  • 31.
    Joosten, Antoine
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Persson, Andreas K. A.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Millet, Renaud
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Johnson, Magnus T.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium(II)-Catalyzed Oxidative Cyclization of Allylic Tosylcarbamates: Scope, Derivatization, and Mechanistic Aspects2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 47, p. 15151-15157Article, review/survey (Refereed)
    Abstract [en]

    A highly selective oxidative palladium(II)-catalyzed (Wacker-type) cyclization of readily available allylic tosylcarbamates is reported. This operationally simple catalytic reaction furnishes tosyl-protected vinyl-oxazolidinones, common precursors to syn-1,2-amino alcohols, in high yield and excellent diasteroselectivity (>20:1). It is demonstrated that both stoichiometric amounts of benzoquinone (BQ) as well as aerobic reoxidation (molecular oxygen) is suitable for this transformation. The title reaction is shown to proceed through overall trans-amidopalladation of the olefin followed by beta-hydride elimination. This process is scalable and the products are suitable for a range of subsequent transformations such as: kinetic resolution (KR) and oxidative Heck-, Wacker-, and metathesis reactions.

  • 32.
    Kalek, Marcin
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Combining Meyer-Schuster Rearrangement with Aldol and Mannich Reactions: Theoretical Study of the Intermediate Interception Strategy2012In: Journal of the American Chemical Society, ISSN 0002-7863, E-ISSN 1520-5126, Vol. 134, no 46, p. 19159-19169Article in journal (Refereed)
    Abstract [en]

    Interception of the transient allenyl enolate intermediate of the vanadium-catalyzed Meyer-Schuster rearrangement with aldehydes and imines has been studied computationally using density functional theory. Mechanistic details of the catalytic cycles for each of the reaction variants are established. In particular, it is shown that the active form of I the catalyst contains two triphenylsiloxy ligands, the transesterification of vanadate occurs via sigma-bond metathesis, and vanadium enolate is directly involved in the key C-C bond formation. The calculations also provide support for the dissociative course of the key 1,3-shift step. The stereochemistry of the reaction is thoroughly investigated, and the obtained energy barriers reproduce and rationalize the experimentally observed (Z)-, (E)-selectivity. The calculated free energy profiles are analyzed in terms of efficiency of the intermediate enolate interception. It is shown that the investigated reactions represent borderline cases, in which the intermediate trapping is only slightly favored over the undesired isomerization pathway.

  • 33. Kotsyubynskyy, Dmytro
    et al.
    Zerbetto, Mirco
    Šoltésová, Mária
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Charles University Prague .
    Engström, Olof
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Pendrill, Robert
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Kowalewski, Josef
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Polimeno, Antonin
    Stochastic Modeling of Flexible Biomolecules Applied to NMR Relaxation: 2. Interpretation of Complex Dynamics in Linear Oligosaccharides2012In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 116, no 50, p. 14541-14555Article in journal (Refereed)
    Abstract [en]

    A computational stochastic approach is applied to the description of flexible molecules. By combining (i) molecular dynamics simulations, (ii) hydrodynamics approaches, and (iii) a multidimensional diffusive description for internal and global dynamics, it is possible to build an efficient integrated approach to the interpretation of relaxation processes in flexible systems. In particular, the model is applied to the interpretation of nuclear magnetic relaxation measurements of linear oligosaccharides, namely a mannose-containing trisaccharide and the pentasaccharide LNF-1. Experimental data are reproduced with sufficient accuracy without free model parameters.

  • 34.
    Laakso, Johanna
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Rosser, Geraldine A.
    Szijjarto, Csongor
    Beeby, Andrew
    Borbas, Eszter
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Synthesis of chlorin sensitized near infrared emitting lanthanide complexes2012In: Inorganic Chemistry, ISSN 0020-1669, E-ISSN 1520-510X, Vol. 51, no 19, p. 10366-10374Article in journal (Refereed)
    Abstract [en]

    Lanthanide (Yb3+, Nd3+) complexes equipped with red-absorbing hydroporphyrin (chlorin) antennae were synthesized and characterized. The syntheses are scalable, highly modular, and enable the introduction of different chlorins functionalized with a single reactive group (COOH or NH2). Absorption maxima were dependent on chlorin substitution pattern (monomeso aryl or dimeso aryl) and metalation state (free base or zinc chelate). The complexes benefit from dual chlorin (610-639 nm) and lanthanide (980 or 1065 nm for Yb- or Nd-complexes, respectively) emission in the biologically relevant red and near IR region of the spectrum.

  • 35.
    Landström, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bergström, Maria
    Hamark, Christoffer
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ohlson, Sten
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Combining weak affinity chromatography, NMR spectroscopy and molecular simulations in carbohydrate-lysozyme interaction studies2012In: Organic and biomolecular chemistry, ISSN 1477-0520, E-ISSN 1477-0539, Vol. 10, no 15, p. 3019-3032Article in journal (Refereed)
    Abstract [en]

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

  • 36.
    Li, Jia-Qi
    et al.
    Uppsala University, Sweden.
    Xu, Quan
    Uppsala University, Sweden.
    Andersson, Pher
    Uppsala University, Sweden; University Of KwaZulu-Natal, South Africa.
    Highly Enantioselective Iridium Catalyzed Hydrogenation of α, β-Unsaturated Esters2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 34, p. 10609-10616Article in journal (Refereed)
    Abstract [en]

    α,β-Unsaturated esters have been employed as substrates in iridium-catalyzed asymmetric hydrogenation. Full conversions and good to excellent enantioselectivities (up to 99 % ee) were obtained for a broad range of substrates with both aromatic- and aliphatic substituents on the prochiral carbon. The hydrogenated products are highly useful as building blocks in the synthesis of a variety of natural products and pharmaceuticals.

  • 37.
    Lihammar, Richard
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Chemoenzymatic Dynamic Kinetic Resolution of Functionalized Secondary Alcohols2012Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dynamic kinetic resolution (DKR) is the combination of a kinetic resolution with an in situ racemization and is a powerful method for obtaining optically active compounds. In this thesis various secondary alcohols are transformed to their corresponding enantiomerically enriched acetates by employing immobilized lipases as resolution catalysts and transition metal complexes as racemization catalysts.

    In the first part 3-hydroxypiperidines and 3-hydroxypyrrolidines are transformed to their corresponding acetates in high yields and high enantiomeric excesses using the DKR method. This was the first report of DKR on these types of N-heterocycles. It was found that the immobilization method used has a significant impact on the enzyme selectivity and reactivity.

    In the second part, cyclic allylic alcohols are investigated as substrates for DKR. After optimization, the amount of enone by-product could be reduced to <10% and a range of allylic alcohols could be converted to enantiomerically pure allylic acetates in high ee. The possibility of further transformation of an iodo-substituted substrate was investigated and initial results obtained are promising. Electron-rich allylic alcohols are not suitable for this method due to competing formation of homo coupled ether.

    DKR has also been applied in the total synthesis of Duloxetine, the active species of the pharmaceutical CymbaltaTM. CymbaltaTM is administered as a drug against physical disorder like depression, stress urinary incontinence, and obsessive compulsive disorder. By performing a sixs tep synthesis, utilizing DKR in the enantiodetermining step, Duloxetine could be isolated in an overall yield of 37% and an enantiomeric excess above 96%.

  • 38.
    Lin, Shuangzheng
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Deiana, Luca
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Tseggai, Abrehet
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cordova, Armando
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Concise Total Synthesis of Dihydrocorynanthenol, Protoemetinol, Protoemetine, 3-epi-Protoemetinol and Emetine2012In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 2, p. 398-408Article in journal (Refereed)
    Abstract [en]

    A concise asymmetric assembly of secologanine tryptamine and dopamine alkaloids by means of a one-pot three-component cascade reaction methodology is disclosed. This is demonstrated by the expeditious total syntheses of (-)-dihydrocorynanthenol, (-)-protoemetinol, (-)-protoemetine, (-)-3-epi-protoemetinol, and emetine (3-6 steps). The biomimetic synthetic strategy involved the following key steps: (i) One-pot three-component highly enantioselective catalytic Michael/Pictet-Spengler/lactamization cascade reactions; (ii) One-pot tandem Swern oxidation/Wittig sequences; (iii) One-pot tandem hydrogenation sequences.

  • 39.
    Lundberg, Helena
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Amidst the green Metal-catalyzed amide formation from carboxylic acids2012Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes novel methods for transition metal-catalyzed transformation of non-activated carboxylic acids to amides. It was found that 2-10 mol% of zirconium(IV) chloride or 10-20 mol% titanium(IV) isopropoxide catalyzed the formation of a range of secondary and tertiary amides in good to excellent yields (61-99%) in THF at 70-100°C, with molecular sieves present as water scavengers. The protocols proved to be suitable for gram scale preparation of amides, where a straight-forward work-up procedure was used for the isolation of the amide products. Furthermore, it was found that ammonium carbamates were suitable equivalents for gaseous ammonia and dimethylamine, in the group (IV) metal-catalyzed amidation of structurally different carboxylic acids, resulting in good to excellent yields (61-99%) of primary and N,N-dimethyl amides.

  • 40.
    Lundberg, Helena
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Tinnis, Fredrik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Direct Amide Coupling of Non-activated Carboxylic Acids and Amines Catalysed by Zirconium(IV) Chloride2012In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 18, no 13, p. 3822-3826Article in journal (Refereed)
  • 41.
    Lundberg, Helena
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Tinnis, Fredrik
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Titanium(IV) Isopropoxide as an Efficient Catalyst for Direct Amidation of Nonactivated Carboxylic Acids2012In: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 23, no 15, p. 2201-2204Article in journal (Refereed)
    Abstract [en]

    Secondary and tertiary amides are formed in high yields, in an efficient and environmentally benign titanium(IV) isopropoxide catalyzed direct amidation of carboxylic acids with primary and secondary amines.

  • 42. Ma, Guangning
    et al.
    Lin, Shuangzheng
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Ibrahem, Ismail
    Kubik, Grzegorz
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Liu, Leifeng
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Sun, Junliang
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK).
    Cordova, Armando
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Achiral Co-Catalyst Induced Switches in Catalytic Asymmetric Reactions on Racemic Mixtures (RRM): From Stereodivergent RRM to Stereoconvergent Deracemization by Combination of Hydrogen Bond Donating and Chiral Amine Catalysts2012In: Advanced Synthesis and Catalysis, ISSN 1615-4150, E-ISSN 1615-4169, Vol. 354, no 14-15, p. 2865-2872Article in journal (Refereed)
    Abstract [en]

    A stereochemical divergent approach for the highly enantioselective synthesis of distinct bicyclic products with multiple stereocenters from a racemate using a single chiral catalyst is disclosed. It is based on switches of the overall reaction pathways in the chiral amine-catalyzed cascade reactions between racemic ?-nitro ketones and a,beta-unsaturated aldehydes using different achiral co-catalysts. The utility of the method is exemplified by the highly diasteroselective switch and stereoconvergent deracemization process by combination of chiral amine and achiral hydrogen-bond-donating catalysts.

  • 43. Moberg, Christina
    et al.
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Concepts in asymmetric catalysis2012In: Israel Journal of Chemistry, ISSN 0021-2148, Vol. 52, no 7 SI, p. 571-571Article in journal (Refereed)
  • 44.
    Nordin, Mikael
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Liao, Rong-Zhen
    Ahlford, Katrin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Adolfsson, Hans
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Himo, Fahmi
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Theoretical study of asymmetric transfer hydrogenation of ketones catalyzed by amino acid derived rhodium complexes2012In: ChemCatChem, ISSN 1867-3880, E-ISSN 1867-3899, Vol. 4, no 8, p. 1095-1104Article in journal (Refereed)
    Abstract [en]

    Density functional theory calculations are employed to study the asymmetric transfer hydrogenation of ketones catalyzed by rhodiumarene complexes containing hydroxamic acid-functionalized amino acid ligands. Firstly, the ligandmetal binding is investigated and it is shown that both the N,N and O,O binding modes Are viable. For each of these, the full free energy profile for the transfer hydrogenation is calculated according to the outer-sphere reaction mechanism. Three factors are demonstrated to influence the stereoselectivity of the process, namely the energy difference between the metalligand binding modes, the energy difference between the intermediate hydrogenated catalyst, and the existence of a stabilizing CHp interaction between the Cp* ligand of the catalyst and the phenyl moiety of the substrate. Theoretical reproduction of the selectivity of a slightly modified ligand that is shown experimentally to yield the opposite enantioselectivity corroborates these results. Finally, a technical observation made is that inclusion of dispersion interactions (using the B3LYP-D2 correction or the M06 functional) proved to be very important for reproducing the enantioselectivity.

  • 45. Norris, Scott E.
    et al.
    Landström, Jens
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Weintraub, Andrej
    Bull, Thomas E.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Freedberg, Darón I.
    Transient hydrogen bonding in uniformly 13C,  15N labeled carbohydrates in water2012In: Biopolymers, ISSN 0006-3525, E-ISSN 1097-0282, Vol. 97, no 3, p. 145-154Article in journal (Refereed)
    Abstract [en]

    We report NMR studies of transient hydrogen bonding in a polysaccharide (PS) dissolved in water without cosolvent at ambient temperature. The PS portion of the Escherichia coli O142 lipopolysaccharide is comprised of repeating pentasaccharide units of GalNAc (N-acetyl galactosamine), GlcNAc (N-acetyl glucosamine), and rhamnose in a 3:1:1 ratio, respectively. A 105-ns molecular dynamics (MD) simulation on one pentasaccharide repeat unit predicts transient inter-residue hydrogen bonds from the GalNAc NH groups in the PS. To investigate these predictions experimentally, the PS was uniformly 13C,15N enriched and the NH, carbonyl, C2, C4, and methyl resonances of the GalNAc and GlcNAc residues assigned using through-bond triple-resonance NMR experiments. Temperature dependence of amide NH chemical shifts and one-bond NH J couplings support that NH groups on two of the GalNAc residues are donors in transient hydrogen bonds. The remaining GalNAc and GlcNAc NHs do not appear to be donors from either temperature-dependent chemical shifts or one-bond NH J couplings. These results substantiate the presence of weak or partial hydrogen bonds in carbohydrates, and that MD simulations of repeating units in PSs provide insight into overall PS structure and dynamics.

  • 46.
    Pershagen, Elias
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Development and applications of lanthanide-based luminescent probes2012Licentiate thesis, comprehensive summary (Other academic)
  • 47.
    Persson, Andreas K. Å.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium(II)-Catalyzed Oxidative Cyclization Strategies: Selective Formation of New C-C and C-N Bonds2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The main focus of this thesis has been directed towards preparation and oxidative carbocyclization of en-, dien- and aza-enallenes.

    In the first part of this thesis, a stereoselective oxidative carbocyclization of dienallenes was realized. By employing cheap and readily available palladium trifluoroacetate we were able to efficiently cyclize a variety of dienallenes into hydroxylated carbocycles in high yield and high selectivity. This oxidative process was compatible with two different reoxidation protocols: one relying on p-benzoquinone (BQ) as the oxidant and the other employing molecular oxygen as the oxidant.

    In the second part of the thesis the carbocyclization methodology was extended to include carbocyclization of aza-enallenes. This was achieved in two distinct steps. First, a copper-catalyzed coupling of allylic sulfonamides with bromoallenes was developed, giving access to the corresponding aza-enallenes. Subjecting these substrates to catalytic amounts of palladium acetate, along with BQ as the oxidant, rendered N-heterocycles in good yield. The reactivity of these N-heterocycles towards activated dienophiles was later exploited in a tandem (aerobic) oxidative carbocyclization/Diels-Alder reaction.

    The third topic involves efficient oxidative arylative/borylative carbocyclization of enallenes. These reactions, catalyzed by palladium acetate, relies on transmetallation of a (σ-alkyl)palladium(II) intermediate with diboranes or arylboronic acids. With this novel methodology we were able to obtain an array of arylated or borylated carbocycles, as single diastereomers, in high yield.

    Finally, we developed a palladium(II)-catalyzed cyclization of allylic carbamates. This mild, operationally simple, and scalable catalytic reaction opens up access to an array of oxazolidinones in high yield and excellent diastereoselectivity.

  • 48.
    Raducan, Mihai
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Alam, Rauful
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Szabo, Kalman J.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Palladium-Catalyzed Synthesis and Isolation of Functionalized Allylboronic Acids: Selective, Direct Allylboration of Ketones2012In: Angewandte Chemie International Edition, ISSN 1433-7851, E-ISSN 1521-3773, Vol. 51, no 52, p. 13050-13053Article in journal (Refereed)
  • 49.
    Rönnols, Jerk
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Burkhardt, Anja
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Cumpstey, Ian
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Widmalm, Göran
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    pK(a)-Determination and Conformational Studies by NMR Spectroscopy of D-Altrose-Containing and other Pseudodisaccharides as Glycosidase Inhibitor Candidates2012In: European Journal of Organic Chemistry, ISSN 1434-193X, E-ISSN 1099-0690, no 1, p. 74-84Article in journal (Refereed)
    Abstract [en]

    The pK(a) values of six amine-linked pseudodisaccharides have been determined by using an NMR-based titration method. The pK(a) varies significantly depending on the linkage position and is inversely correlated with the number of electronegative groups in the beta-position to the amino group. Four of the pseudodisaccharides contain alpha-altroside moieties, the conformations of which were determined in the protonated and neutral states, again by using NMR techniques. In the neutral state, 2-amino-2-deoxyaltrosides and 3-amino-3-deoxyaltrosides were both found to occupy C-4(1) and S-O(2) conformations. On protonation, little change in the population distribution was seen for the 3-amino-3-deoxyaltrosides, but for the 2-amino-2-deoxyaltrosides, a shift in equilibrium position towards the skew conformer (more than 80% populated) takes place, and also a small amount of the other chair conformer (i.e., C-1(4), approximately 10% populated) was observed. 3-Amino-3-deoxyaltrosides have been shown to act as glycosidase inhibitors and insights into conformational equilibria as a function of protonation state should facilitate the design of better glycosidase inhibitors based on flexible monosaccharide amines.

  • 50.
    Sandström, Anders G.
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Wikmark, Ylva
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Engström, Karin
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Nyhlén, Jonas
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Bäckvall, Jan-E.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Combinatorial reshaping of the Candida antarctica lipase A substrate pocket for enantioselectivity using an extremely condensed library2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 1, p. 78-83Article in journal (Refereed)
    Abstract [en]

    A highly combinatorial structure-based protein engineering method for obtaining enantioselectivity is reported that results in a thorough modification of the substrate binding pocket of Candida antarctica lipase A (CALA). Nine amino acid residues surrounding the entire pocket were simultaneously mutated, contributing to a reshaping of the substrate pocket to give increased enantioselectivity and activity for a sterically demanding substrate. This approach seems to be powerful for developing enantioselectivity when a complete reshaping of the active site is required. Screening toward ibuprofen ester 1, a substrate for which previously used methods had failed, gave variants with a significantly increased enantioselectivity and activity. Wild-type CALA has a moderate activity with an E value of only 3.4 toward this substrate. The best variant had an E value of 100 and it also displayed a high activity. The variation at each mutated position was highly reduced, comprising only the wild type and an alternative residue, preferably a smaller one with similar properties. These minimal binary variations allow for an extremely condensed protein library. With this highly combinatorial method synergistic effects are accounted for and the protein fitness landscape is explored efficiently.

12 1 - 50 of 68
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