Synthesis of a 7-Membered Biaryl Guanidine Catalyst and its Use in the Vinylogous Aldol Reaction

The present thesis outlines the preparation of a 7-membered guanidine. Initial efforts to obtain this guanidine via 2-chloro-1,3-dimethylimidazolinium chloride induced ring forming chemistry failed to provide the target in a reproducible fashion. Changing strategies, we were able to obtain the desired guanidine through CuCl mediated amination of a 7-membered thiourea intermediate to arrive at the target. In addition, the catalytic activity of this compound was evaluated in a vinylogous aldol reaction of dibromofuranone and four aromatic aldehydes to generate chiral γ-butenolides with modest to good enantiomeric excess. It was found that electron-poor aldehydes resulted in higher, 81% ee, whereas electron rich aldehydes led to low, 41% ee, levels of enantiomeric excess.

Transient and Pulsed Electron Paramagnetic Resonance Spectroscopy on Type I Photosynthetic Reaction Centers

Two time-resolved EPR techniques, have been used to study the light induced electron transfer(ET) in Type I photosynthetic reaction centers(RCs). First, pulsed EPR was used to compare PsaA-M688H and PsaB-M668H mutants of Chlamydomonas reinhardtii and Synechosystis sp. PCC 6803.The out-of-phase echo modulation curves combined with other EPR and optical data show that the effect of the mutations is species dependent. Second, transient and pulsed EPR data are presented which show that PsaA-A660N and PsaB-A640N mutations in C. reinhardtii alter the relative quantum yield of ET in the A- and B-branches of PS I. Third, transient EPR studies on RCs from Heliobacillus mobilis that have been exposed to oxygen show partial inhibition of ET. In the RCs in which ET still occurs, the ET kinetics and EPR spectra show evidence of oxidation of some but not all of the, BChl g and BChl g' to Chl a.

(A) Photoregulation of DNA Functions by Cyclic Azobenzene-tethered Oligonucleotides (B) Site-specific Fluorescent Labeling of DNA using Inverse Electron Demand Diels-Alder Reaction between trans-Cyclooctene Derivatives and BODIPY-Tetrazine Adducts

(A) Most azobenzene-based photoswitches require UV light for photoisomerization, which limit their applications in biological systems due to possible photodamage. Cyclic azobenzene derivatives, on the other hand, can undergo cis-trans isomerization when exposed to visible light. A shortened synthetic scheme was developed for the preparation of a building block containing cyclic azobenzene and D-threoninol (cAB-Thr). trans-Cyclic azobenzene was found to thermally isomerize back to the cis-form in a temperature-dependent manner. cAB-Thr was transformed into the corresponding phosphoramidite and subsequently incorporated into oligonucleotides by solid phase synthesis. Melting temperature measurement suggested that incorporation of cis-cAB into oligonucleotides destabilizes DNA duplexes, these findings corroborate with circular dichroism measurement. Finally, Fluorescent Energy Resonance Transfer experiments indicated that trans-cAB can be accommodated in DNA duplexes. (B) Inverse Electron Demand Diels-Alder reactions (IEDDA) between trans-olefins and tetrazines provide a powerful alternative to existing ligation chemistries due to its fast reaction rate, bioorthogonality and mutual orthogonality with other click reactions. In this project, an attempt was pursued to synthesize trans-cyclooctene building blocks for oligonucleotide labeling by reacting with BODIPY-tetrazine. Rel-(1R-4E-pR)-cyclooct-4-enol and rel-(1R,8S,9S,4E)-Bicyclo[6.1.0]non-4-ene-9-ylmethanol were synthesized and then transformed into the corresponding propargyl ether. Subsequent Sonogashira reactions between these propargylated compounds with DMT-protected 5-iododeoxyuridine failed to give the desired products. Finally a methodology was pursued for the synthesis of BODIPY-tetrazine conjugates that will be used in future IEDDA reactions with trans-cyclooctene modified oligonucleotides.

Approach to the Synthesis of Aza-Analogues of Narciclasine through an Intramolecular Heck Reaction

This thesis describes work towards the total synthesis of a 7-aza analogue of the Amaryllidaceae alkaloid narciclasine, a potent anticancer compound which suffers from a poor solubility profile. A key strategy in the formation of the C-ring is the biotransformation of bromobenzene by E.coli JM109. The densely substituted heterocyclic A-ring is obtained by sequential directed ortho-metalation and the fragment union accomplished with an amide coupling and subsequent intramolecular Heck reaction.

DFT Studies of the Organocatalytic Aldol Reaction and a Frustrated Lewis Pair

The computational study, and in particular the density functional theory (DFT) study of the organocatalytic α-chlorination-aldol reaction and the chiral backbone Frustrated Lewis Pair (FLP) system served as a valuable tool for experimental purposes. This thesis describes methods to consider different transition states of the proline- catalyzed α-chlorination aldol reaction to determine the reasonable transition state in the reaction between the enamine and α-chloro aldehydes. Moreover, the novel intramolecular Frustrated Lewis pair based on a chiral backbone for the asymmetric hydrogenation of imines and enamines was designed and the ability of hydrogen splitting by this new FLP system was examined by computational modeling and calculating the hydrogen activation energy barrier.

Politics in extraordinary times : a study of the reaction of political parties and elites to terrorism

Cette thèse porte sur le comportement des élites politiques durant les périodes de crise nationale et plus particulièrement sur leurs réactions aux attentats terroristes. Elle démontre que les crises terroristes sont tout comme les conflits militaires ou diplomatiques propices aux unions nationales et notamment aux ralliements des partis d’opposition auprès du gouvernement. L’analyse statistique d’actes terroristes s’étant produits dans cinq états démocratiques (Allemagne, Espagne, États-Unis d’Amérique, France et Royaume-Uni) entre 1990 et 2006 révèle que l’ampleur d’un attentat en termes de pertes humaines ainsi que la répétition de ces attentats influencent dans une large mesure la réaction des élites politiques. Ainsi plus l’ampleur d’un attentat est élevée, plus la probabilité d’un ralliement est grande. En revanche, la multiplication des attentats augmente la possibilité de dissension entre l’opposition et le gouvernement. Par ailleurs, l’opposition est plus susceptible de se rallier au gouvernement lorsque l’attentat est perpétré par des terroristes provenant de l’étranger. L’analyse quantitative indique également que l’existence d’un accord formel de coopération dans la lutte antiterroriste entre le gouvernement et l’opposition favorise l’union des élites. Enfin, les données analysées suggèrent que la proportion des ralliements dans les cinq pays est plus importante depuis les attentats du 11 septembre 2001. Une analyse qualitative portant exclusivement sur la France et couvrant la période 1980-2006 confirme la validité des variables identifiées dans la partie quantitative, mais suggère que les élites réagissent au nombre total de victimes (morts mais aussi blessés) et que la répétition des actes terroristes a moins d’impact lors des vagues d’attentats. Par ailleurs, les analyses de cas confirment que les élites politiques françaises sont plus susceptibles de se rallier quand un attentat vise un haut-fonctionnaire de l’État. Il apparaît également que les rivalités et rancœurs politiques propre à la France (notamment suite à l’arrivée de la gauche au pouvoir en 1981) ont parfois empêché le ralliement des élites. Enfin, cette analyse qualitative révèle que si l’extrême gauche française soutient généralement le gouvernement, qu’il soit de gauche ou de droite, en période de crise terroriste, l’extrême droite en revanche saisit quasi systématiquement l’opportunité offerte par l’acte terroriste pour critiquer le gouvernement ainsi que les partis de l’establishment. La thèse est divisée en sept chapitres. Le premier chapitre suggère que le comportement des élites politiques en période de crises internationales graves (guerres et conflits diplomatiques) est souvent influencé par la raison d’État et non par l’intérêt électoral qui prédomine lors des périodes plus paisibles. Le second chapitre discute du phénomène terroriste et de la littérature afférente. Le troisième chapitre analyse les causes du phénomène d’union nationale, soumet un cadre pour l’analyse de la réaction des élites aux actes terroristes, et présente une série d’hypothèses. Le quatrième chapitre détaille la méthodologie utilisée au cours de cette recherche. Les chapitres cinq et six présentent respectivement les résultats des analyses quantitatives et qualitatives. Enfin, le chapitre sept conclut cette thèse en résumant la contribution de l’auteur et en suggérant des pistes de recherche.

Evaluation of multiple reaction monitoring cubed for the analysis of tachykinin related peptides in rat spinal cord using a hybrid triple quadrupole–linear ion trap mass spectrometer

Targeted peptide methods generally use HPLC-MS/MRM approaches. Although dependent on the instrumental resolution, interferences may occur while performing analysis of complex biological matrices. HPLC-MS/MRM3 is a technique, which provides a significantly better selectivity, compared with HPLC-MS/MRM assay. HPLC-MS/MRM3 allows the detection and quantitation by enriching standard MRM with secondary product ions that are generated within the linear ion trap. Substance P (SP) and neurokinin A (NKA) are tachykinin peptides playing a central role in pain transmission. The objective of this study was to verify whether HPLC-HPLCMS/ MRM3 could provide significant advantages over a more traditional HPLC-MS/MRM assay for the quantification of SP and NKA in rat spinal cord. The results suggest that reconstructed MRM3 chromatograms display significant improvements with the nearly complete elimination of interfering peaks but the sensitivity (i.e. signal-to-noise ratio) was severely reduced. The precision (%CV) observed was between 3.5% - 24.1% using HPLC-MS/MRM and in the range of 4.3% - 13.1% with HPLC-MS/MRM3, for SP and NKA. The observed accuracy was within 10% of the theoretical concentrations tested. HPLC-MS/MRM3 may improve the assay sensitivity to detect difference between samples by reducing significantly the potential of interferences and therefore reduce instrumental errors.

Development and use of a multiplex real-time quantitative polymerase chain reaction assay for detection and differentiation of Porcine circovirus-2 genotypes 2a and 2b in an epidemiological survey.

By the end of 2004, the Canadian swine population had experienced a severe 2 increase in the incidence of Porcine circovirus-associated disease (PCVAD), a problem that was 3 associated with the emergence of a new Porcine circovirus-2 genotype (PCV-2b), previously 4 unrecovered in North America. Thus it became important to develop a diagnostic tool that could 5 differentiate between the old and new circulating genotypes (PCV-2a and -2b, respectively). 6 Consequently, a multiplex real-time quantitative polymerase chain reaction (mrtqPCR) assay that 7 could sensitively and specifically identify and differentiate PCV-2 genotypes was developed. A 8 retrospective epidemiological survey that used the mrtqPCR assay was performed to determine if 9 cofactors could affect the risk of PCVAD. From 121 PCV-2–positive cases gathered for this 10 study, 4.13%, 92.56% and 3.31% were positive for PCV-2a, PCV-2b, and both genotypes, 11 respectively. In a data analysis using univariate logistic regressions, PCVAD compatible 12 (PCVAD/c) score was significantly associated with the presence of Porcine reproductive and 13 respiratory syndrome virus (PRRSV), PRRSV viral load, PCV-2 viral load, and PCV-2 14 immunohistochemistry (IHC) results. Polytomous logistic regression analysis revealed that 15 PCVAD/c score was affected by PCV-2 viral load (P = 0.0161) and IHC (P = 0.0128), but not by 16 the PRRSV variables (P > 0.9); suggesting that mrtqPCR in tissue is a reliable alternative to IHC. 17 Logistic regression analyses revealed that PCV-2 increased the odds ratio of isolating 2 major 18 swine pathogens of the respiratory tract, Actinobacillus pleuropneumoniae and Streptococcus 19 suis serotypes 1/2, 1, 2, 3, 4, and 7, which are serotypes commonly associated with clinical 20 diseases.

Ruthenium complexes of Schiff base ligands as efficient catalysts for catechol–hydrogen peroxide reaction

Zeolite Y-encapsulated ruthenium(III) complexes of Schiff bases derived from 3-hydroxyquinoxaline-2-carboxaldehyde and 1,2- phenylenediamine, 2-aminophenol, or 2-aminobenzimidazole (RuYqpd, RuYqap and RuYqab, respectively) and the Schiff bases derived from salicylaldehyde and 1,2-phenylenediamine, 2-aminophenol, or 2-aminobenzimidazole (RuYsalpd, RuYsalap and RuYsalab, respectively) have been prepared and characterized. These complexes, except RuYqpd, catalyze catechol oxidation by H2O2 selectively to 1,2,4-trihydroxybenzene. RuYqpd is inactive. A comparative study of the initial rates and percentage conversion of the reaction was done in all cases. Turn over frequency of the catalysts was also calculated. The catalytic activity of the complexes is in the order RuYqap > RuYqab for quinoxaline-based complexes and RuYsalap > RuYsalpd > RuYsalab for salicylidene-based complexes. The reaction is believed to proceed through the formation of a Ru(V) species.

Three Component Mannich Reaction and 1,5-Benzodiazepine Synthesis Catalyzed by a Tetranitrile-Silver Complex

This manuscript describes the first example of silver ion complex of a dendritic tetranitrile ligand catalyzed one-pot three component Mannich reaction and 1,5-benzodiazepine synthesis. The catalyst can be separated from the products by a change in the solvent. The catalyst is reusable.

Study of cyclohexanol decomposition reaction over the ferrospinels, A1−xCuxFe2O4 (A=Ni or Co and x=0, 0.3, 0.5, 0.7 and 1), prepared by ‘soft’ chemical methods

Preparation of simple and mixed ferrospinels of nickel, cobalt and copper and their sulphated analogues by the room temperature coprecipitation method yielded fine particles with high surface areas. Study of the vapour phase decomposition of cyclohexanol at 300 °C over all the ferrospinel systems showed very good conversions yielding cyclohexene by dehydration and/or cyclohexanone by dehydrogenation, as the major products. Sulphation very much enhanced the dehydration activity over all the samples. A good correlation was obtained between the dehydration activities of the simple ferrites and their weak plus medium strength acidities (usually of the Brφnsted type) determined independently by the n-butylamine adsorption and ammonia-TPD methods. Mixed ferrites containing copper showed a general decrease in acidities and a drastic decrease in dehydration activities. There was no general correlation between the basicity parameters obtained by electron donor studies and the ratio of dehydrogenation to dehydration activities. There was a leap in the dehydrogenation activities in the case of all the ferrospinel samples containing copper. Along with the basic properties, the redox properties of copper ion have been invoked to account for this added activity.

Synthesis of dimethyl acetal of ketones: design of solid acid catalysts for one-pot acetalization reaction

The synthesis of dimethyl acetals of carbonyl compounds such as cyclohexanone, acetophenone, and benzophenone has successfully been carried out by the reaction between ketones and methanol using different solid acid catalysts. The strong influence of the textural properties of the catalysts such as acid amount and adsorption properties (surface area and pore volume) determine the catalytic activity. The molecular size of the reactants and products determine the acetalization ability of a particular ketone. The hydrophobicity of the various rare earth exchanged Mg–Y zeolites, K-10 montmorillonite clay, and cerium exchanged montmorillonite (which shows maximum activity) is more determinant than the number of active sites present on the catalyst. The optimum number of acidic sites as well as dehydrating ability of Ce3+-montmorillonite and K-10 montmorillonite clays and various rare earth exchanged Mg–Y zeolites seem to work well in shifting the equilibrium to the product side.

Studies on the Solvent Dependence in the Reaction of a Few (Anthracen-9-yl)MethyLamines and Sulfanes with Reactive Acetylenes

The thesis entitled ‘Studies on the Solvent Dependence in the Reaction of a Few (Anthracen-9-yl)methylamines and Sulfanes with Reactive Acetylenes’ is divided into six chapters. ln Chapter l a general survey of electron transfer reactions, Diels-Alder reactions and Michael-type additions is presented. A detailed discussion on the synthesis of several (anthracen-9-yl)methylamines is presented in Chapter 2. In Chapter 3, results of preliminary photophysical studies on a few (anthracen-9yl) methylamines are compiled. A detailed discussion on extensive examination of dependence in the reaction of (anthracen-9-yl)methylamines with reactive acetylenes is presented Chapter 4. Details on the synthesis and reaction of a few (anthracen-9-yl)methylsulfanes with DMAD are described in Chapter 5.