<p>The ability of amino acids to form nucleophilic enamines with aldehydes and ketones has been used in the development of asymmetric <i>α</i>-oxidation reactions with electrophilic oxidizing agents. Singlet molecular oxygen has for the first time been asymmetrically incorporated into aldehydes and ketones, and the products were isolated as their corresponding diols in good yields and <i>ee</i>’s. Organocatalytic <i>α</i>-oxidations of cyclic ketones with iodosobenzene and <i>N</i>-sulfonyloxaziridine were also possible and furnished after reduction the product diols in generally low yields and in low to good <i>ee</i>’s. Amino acids have also been shown to catalyze the formation of carbohydrates by sequential aldol reactions. For example, proline and hydroxy proline mediate a highly selective trimerisation of <i>α</i>-benzyloxyacetaldehyde into allose, which was obtained in >99 % <i>ee</i>. Non linear effect studies of this reaction revealed the largest permanent nonlinear effect observed in a proline-catalyzed reaction to date. Moreover, polyketides were also assembled in a similar fashion by an amino acid-catalyzed one-pot reaction, and was successful for the trimerisation of propionaldehyde, however the sequential cross aldol reactions suffered from lower selectivities. This problem was overcome by the development of a two-step synthesis that enabled the formation of a range of polyketides with excellent selectivities from a variety of aldehydes. The method furnishes the polyketides via the shortest route reported and in comparable product yields to most multi-step synthesis. All polyketides were isolated as single diastereomers with >99 % <i>ee</i>. Based on the observed amino acid-catalysis, amino acids are thought to have taken part in the prebiotic formation of tetroses and hexoses.</p>

<p>This licentiate thesis is based on the development of catalytic reactions for the synthesis and application of organometallic reagents. By use of palladium pincer-complex catalysts, we have developed an efficient procedure for the synthesis of allylboronates starting from allylic alcohols. These reactions were further extended by including various one-pot multi-component reactions, using the in situ generated allylboronates. Furthermore, novel unsymmetrical palladium pincer-complexes were synthesized and studied in auto-tandem catalysis.</p>

This licentiate thesis is based on the development of catalytic reactions for the synthesis and application of organometallic reagents. By use of palladium pincer-complex catalysts, we have developed an efficient procedure for the synthesis of allylboronates starting from allylic alcohols. These reactions were further extended by including various one-pot multi-component reactions, using the in situ generated allylboronates. Furthermore, novel unsymmetrical palladium pincer-complexes were synthesized and studied in auto-tandem catalysis.

The ability of amino acids to form nucleophilic enamines with aldehydes and ketones has been used in the development of asymmetric α-oxidation reactions with electrophilic oxidizing agents. Singlet molecular oxygen has for the first time been asymmetrically incorporated into aldehydes and ketones, and the products were isolated as their corresponding diols in good yields and ee’s. Organocatalytic α-oxidations of cyclic ketones with iodosobenzene and N-sulfonyloxaziridine were also possible and furnished after reduction the product diols in generally low yields and in low to good ee’s. Amino acids have also been shown to catalyze the formation of carbohydrates by sequential aldol reactions. For example, proline and hydroxy proline mediate a highly selective trimerisation of α-benzyloxyacetaldehyde into allose, which was obtained in &gt;99 % ee. Non linear effect studies of this reaction revealed the largest permanent nonlinear effect observed in a proline-catalyzed reaction to date. Moreover, polyketides were also assembled in a similar fashion by an amino acid-catalyzed one-pot reaction, and was successful for the trimerisation of propionaldehyde, however the sequential cross aldol reactions suffered from lower selectivities. This problem was overcome by the development of a two-step synthesis that enabled the formation of a range of polyketides with excellent selectivities from a variety of aldehydes. The method furnishes the polyketides via the shortest route reported and in comparable product yields to most multi-step synthesis. All polyketides were isolated as single diastereomers with &gt;99 % ee. Based on the observed amino acid-catalysis, amino acids are thought to have taken part in the prebiotic formation of tetroses and hexoses.

This thesis presents the development of new palladium-catalyzed transformations involving synthesis and application of allylborane reagents. In these reactions various palladium sources, including pincer complexes and commonly used catalysts were applied. A new transformation for allylation of aldehyde and imine substrates was devised using allyl acetates, diboronate reagents and catalytic amounts of Pd2(dba)3. By employment of commercially available chiral diboronates enantioenriched homoallyl alcohols could be obtained. We have also developed a palladium-catalyzed method for synthesis of functionalized allylboronic acids from vinyl cyclopropane, vinyl aziridine, allyl acetate and allyl alcohol substrates using diboronic acid as reagent. In this process a highly selective selenium based pincer-complex was used as catalyst. The resulting allylboronic acid products were converted to potassium trifluoro(allyl)borates or allylboronates. The functionalized allylboronic acids generated in the above procedure were employed as reagents in two synthetic transformations. One of these transformations involves a palladium(0)-catalyzed coupling reaction between allylboronic acids and aryl iodides. The reaction was regioselective for the branched allylic product, typically difficult to prepare in the absence of directing groups. We also developed another transformation for allylation of aldehydes with allyl alcohols via allylboronic acid intermediate. This procedure can be performed as a simple one-pot sequence affording homoallyl alcohols with excellent stereo- and regioselectivity.

Glutathione transferases (GSTs) play a pivotal role in cellular defense, since they are main contributors to the inactivation of genotoxic compounds of exogenous and endogenous origins. Directed evolution was used to improve the catalytic activities of Theta class GST T1-1 toward different substrates. The library was constructed by recombination of cDNA coding for human GST T1-1 and rodent Theta class GSTs, resulting in the F2-F5 generations. The clones were heterologously expressed in Escherichia coli and screened for variants with enhanced alkyltransferase activity. A mutant, F2:1215, with a 70-fold increased catalytic efficiency with 4-nitrophenethyl bromide (NPB) compared to human GST T1-1, was isolated from the second generation. NPB was used as a surrogate substrate of the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in order to facilitate the screening process. The catalytic efficiency of the F2:1215 with BCNU had improved 170-fold compared to wild-type human GST T1-1, suggesting that NPB is a suitable model substrate for the anticancer drug BCNU. The sequence of the F2:1215 mutant differs from wild-type human GST T1-1 by three residues; one of these differences is Arg234, which corresponds to Trp in the human enzyme. Upon replacing the Trp234 in the human GST T1-1 with Arg, the resulting mutant (hTrp234Arg) showed enhanced alkyltransferase activity with a wide range of substrates (e.g. haloalkanes and other typical GSTs substrates). The three-dimensional structures of both wild-type human GST T1-1 and hTrp234Arg mutant help to explain the higher activity showed by of hTrp234Arg mutant compared to wild-type enzyme. The reciprocal mutation of the residue 234 in mouse GST T1-1 to that found in human, mArg234Trp, caused a dramatic decrease in the activity of the mouse enzyme to be similar to human GST T1-1. This indicates that residue 234 can be considered as a master switch of activities between human and rodent GST T1-1. Another important residue in the C-terminal helix of GST T1-1 is Met232. Although residue 232 points away from the H-site, it influences the catalytic activity and substrate selectivity of the mouse GST T1-1. A minor modification of Met232 induces major changes in the substrate-activity profile of the mouse GST T1-1 to favor novel substrates such as isothiocyanates and hydroperoxides and decreases the activity toward substrates that catalyzed by the wild-type enzyme.

This thesis deals with the study of oxazoline-based ligands in metal-catalyzed asymmetric reactions. The first part describes the synthesis of six new bifunctinal pyridine-bis(oxazoline) ligands and their applications in asymmetric metal-catalysis. These ligands, in addition to a Lewis acid coordination site, are equipped with a Lewis basic part in the 4-position of the oxazoline rings. Dual activation by means of this system was probed in cyanide addition to aldehydes. The second part is concerned with the synthesis of two pyridine-bis(oxazoline) ligands bearing bulky triazole groups in the 4-position of the oxazoline rings and a macrocyclic ligand consisting of a pyridine-bis(oxazoline) moiety and a diaza-18-crown-6 ether. The synthesis of these compounds benefits from the use of “click chemistry”. The ligands thus obtained were tested in different asymmetric catalytic reactions. Complexation studies with different bifunctional molecules that could bind into the cavity of the macrocycle were carried out using NMR spectroscopy. A third chapter is devoted to the synthesis of a supported pyridine-bis(oxazoline) catalyst and its use in catalysis. The pyridine-bis(oxazoline) ligand was efficiently connected to a polystyrene resin via a robust triazole linker. This resin could be employed in different metal-catalyzed asymmetric reactions and good results were obtained in terms of yield and enantioselectivity. Moreover, this polymer-bound ligand could be easily and efficiently recycled. Finally, the last part deals with the use of a hydroxy-containing phosphinooxazoline ligand in the hydrosilylation of imines and in the asymmetric intermolecular Heck reaction. A cationic iridium complex of this ligand was studied by NMR spectroscopy. / QC 20100914

Today there are strict demands regarding emissions to water and air from the Swedish industries. This degree project, conducted at Smurfit Kappa Piteå, will focus on the emissions of organic material in waste water from the paper mill. The overall goal was through dynamic simulations predict the Total Organic Carbon (TOC) emissions from the paper mill at the time a foreseen increase of production is implemented. The recovery boiler is currently a bottleneck in the process and the production of sulphate pulp has today its maximum capacity. This means that production growth will occur exclusively by increasing the intake of recycled fiber. The work started with a comprehensive mapping of TOC, in which ingoing pulps in pulp towers, head boxes and effluent flows were mapped. This was done over a period of two weeks and thus covered a whole production cycle. A TOC method evaluation was conducted where the most suitable analysis method was determined. Mapped data were thereupon evaluated and significant variables were identified. It was determined that use of recycled fiber was the single most important variable to TOC load from paper machine 1 (PM1), but also starch addition to paper machine 2 (PM2) was found to be significant. The work then continued with the simulation phase, consisting of two main parts. The first part consisted of preparatory work where the model was developed to be able to accurately measure TOC load to the waste water treatment plant. This part also included work to identify necessary process changes as a result of an increased production. The second part consisted of the simulation. Three different scenarios were simulated for each paper machine plus two scenarios for the recycled fiber plant. The dynamic simulation model was successively calibrated with respect to TOC concentration and trends followed the ones expected by experience. In the production increase scenario simulated, TOC load distribution between PM1, PM2 and recycled fiber plant will more evenly distributed compared to current production. The largest increase of TOC load will come from the recycled fiber plant, which according to the simulation will increase with about 30 %. / Idag ställs höga krav på de svenska industrierna vad avser utsläpp till vatten och luft. I detta examensarbete som utförts på Smurfit Kappa Piteå undersöktes avloppsflöden från pappersbruket till bioreningsanläggningen. Den övergripande målsättningen var att genom dynamiska simuleringar prediktera de TOC utsläpp pappersbruket kommer att generera efter planerad produktionsökning. Sodapannan är i dagsläget en flaskhals i processen, något som medför att produktionen av nyfibermassa idag så hög den kan vara. Detta medför att produktionsökningen uteslutande kommer att bestå av ökat intag av returfibermassa. Arbetet startade med en omfattande TOC kartering där ingående massor, inloppslådor samt avloppsflöden karterades. Detta utfördes under två veckor och täckte på så sätt en hel produktionscykel. En metodutvärdering genomfördes där lämplig metod för att mäta TOC i just de karterade provpunkterna bestämdes. Erhållna data från karteringen analyserades därpå och signifikanta variabler utvärderades. Det konstaterades att användningen av returfibermassa var den enskilt mest korrelerade variabeln till TOC nivå för pappersmaskin 1 (PM1), samt att stärkelsetillsats på pappersmaskin 2 (PM2) påvisades vara signifikant under den karterade perioden. Simuleringsfasen tog sedan vid, vilken bestod av två delar. En del bestod av förberedande arbete där modellen utvecklades för att simulera TOC halt med så god precision som möjligt. I denna del ingick även arbete för att ta fram nödvändiga processförändringar i och med den ökade produktionen. Den andra delen bestod av själva simuleringsfasen där tre olika scenarion simulerades för respektive pappersmaskin samt två stycken för returfiberanläggningen. Den dynamiska simuleringsmodellen lyckades på ett bra sätt balanseras med karterade mätdata. De utförda simuleringarna av TOC belastning till bioreningen påvisade rimliga resultat och följde de trender som erfarenhetsmässigt kan förklaras. Vid den simulerade produktionsökningen scenariot kommer TOC fördelningen mellan PM1, PM2 och returfiberanläggningen vara mer jämnt fördelat. Den största ökningen av TOC belastning kommer från returfiberanläggningen som enligt simuleringen kommer att öka med omkring 30 %.

Acrylfentanyl is a synthetic opioid that has been widely used in the last year. To help in the fight against synthetic drugs two potential metabolites of acrylfentanyl, one monohydroxy and one dihydroxy were synthesized. These metabolites will hopefully later be implemented in the analytical methods for metabolites of acrylfentanyl in urine by the Swedish National Board of Forensic Medicine. To have metabolites for analysis are very important as they are the main target in drug testing. The method used to synthesize the metabolites is a five-step synthesis with an additional 6th step for the dihydroxy metabolite. The methods used in the synthesis includes protection of amine with tert-butyloxycarbonyl, reductive amination with sodium triaceto boronhydride, alkylation and demethylation with boron tribromide. The methods used produced good results with high yields in nearly all steps.

No description available.