Made available in DSpace on 2015-05-14T13:21:20Z (GMT). No. of bitstreams: 1 ArquivoTotal.pdf: 3274931 bytes, checksum: fad3ac5b146d775c69dcf930c8894e4e (MD5) Previous issue date: 2013-08-21 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / This work aimed to perform the kinetic bioresolution of Morita Baylis Hillman adducts (MBHA) using CALB lipase derived from Candida Antarctica fungus. Initially three MBHA we synthesized using acrylonitrile and m e p nitro benzaldehyde. Subsequently the respective acetates from MBHA were prepared in high yields using acetyl chloride and TEA. Methodologies for bioresolution of AMBH (obtained from nitro aldehydes m e p) were successfully developed producing the R enantiomers with 99.9% of enantiomeric excess determined by gas chromatography (using the beta cyclodextrin chiral column). However, using the same methodology it was not possible performed the bioresolution of AMBH derived from the o-benzaldehyde. To obtain the S enantiomers, the hydrolysis reactions of esters obtained from biocatalysis were made and separated by liquid chromatography. These hydrolysis reactions were carried out using K2CO3 and methanol, yielding the S enantiomers with 100% and 10% of chemical yields and 86.8% and 97.48% of enantiomeric excesses respectively. Using the method of Mosher through double derivatization chemical shift values obtained from 1H NMR spectra generated a NORS> and NORS 0 <0, which indicates that the absolute configuration of the asymmetric carbon of AMBH hydrolyzed by enzyme is R. The values of [S] D derived from m and p nitro aldehydes (S configuration) are +37 and +30 degrees. The values of [S] D of S corresponding acetates are -7 and -9 degrees respectively. The AMBH obtained from the m nitro aldehyde were bioavaliados in vitro in a R/S, R and S forms. The racemate was the most effective on L. braziliensis promastigotes and the S enantiomer was the lowest active. In the cell cytotoxicity analysis which were evaluated in the safe murine macrophages, the racemate was the most cytotoxic and the S enantiomer the less cytotoxic (some cytotoxicity were only observed at concentrations over 40 mg/mL) concluding that all evaluated compounds were more cytotoxic for L. braziliensis parasite that the safe macrophage. / Nesse trabalho visou-se a bio-resolução cinética dos Adutos de Morita Baylis Hillman (AMBH) utilizando a Lipase CALB derivada do fungo Candida Antarctica. Inicialmente foram sintetizados três AMBH usando acrilonitrila e os respectivos o, m e p nitrobenzaldeídos. Subsequentemente os seus respectivos acetatos foram preparados em altos rendimentos, usando cloreto de acetila e TEA. Foram desenvolvidas com êxito, metodologias para a bio-resolução dos AMBH oriundos dos nitroaldeídos m e p, obtendo os enantiômeros R com excessos enantioméricos de 99,9%, determinados pela técnica de cromatografia gasosa, usando à coluna quiral beta ciclodextrina e fase móvel (N2). Porém usando as metodologias acima não foi possível a bio-resolução do AMBH derivado do o-benzaldeído. Para obter os enantiômeros S, foram feitas as reações de hidrólise dos respectivos ésteres devidamente separados por cromatografia líquida das reações de biocatálise. As reações de hidrólise foram feitas usando K2CO3 e metanol, obtendo-se os enantiômeros S com rendimentos químicos de 100% e 10% e excessos enantioméricos de 86,8% e 97,48% respectivamente. Usando o método de Mosher através da dupla derivatização os valores de deslocamentos químicos obtidos dos espectros de RMN1H geraram um NORS>0 e NORS<0, o que demonstra que a configuração absoluta do carbono assimétrico dos AMBH os quais a enzima hidrolisou é R. Os valores de [S]D oriundos dos AMBH nitroaldeídos m e p (configuração R) são +37 e +30. Os valores de [S]D dos correspondentes acetatos S são -7 e -9 respectivamente. O AMBH oriundo do m-nitroaldeído nas formas R/S, R e S foram bioavaliados in vitro. A mistura racêmica foi a que se apresentou mais efetiva sobre promastigotas de L. braziliensis, e a substância S foi a que apresentou a menor atividade. Na análise de citotoxicidade celular no macrófago sadio de murinos observou-se que a mistura racêmica foi a mais citotóxica e o S o menos citotóxico (citotoxidade apenas a partir da concentração de 40 Xg/mL) constatando que todas as substâncias avaliadas foram mais citotóxicas para o parasita do que para macrófagos.

Made available in DSpace on 2015-05-14T13:21:44Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 4637140 bytes, checksum: f9c50e9a2115f5a805442d163ed54f1e (MD5) Previous issue date: 2012-12-14 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The Morita-Baylis-Hillman Adducts (MBHA) is a class of molecules studied by our research group on synthetic, theoretical and bioactivity aspects. In this work, we present Quantitative Structure-Activity Relationship (QSAR) models involving 32 aromatic MBHA. Initially, the most stable conformations of thirty-two MBHA were investigated by theoretical methods, which were used to construct models. For this study, were obtained potential energy curves using AM1 semi-empirical method, considering rotational degrees of freedom (sigma bonds). From these curves, the less energy conformation to each molecule was selected and optimized at B3LYP/6- 31+G(d) level, considering solvent effects through Polarizable Continuum Model (PCM). Proton Nuclear Magnetic Ressonance data are in agreement with the conformational study. Intramolecular Hydrogen Bonds (IHB) are presents in the most of the studied compounds, according to structural characterization and QTAIM calculations. Curiously, compounds that showed hydrogen bonds involving the nitro and hydroxyl groups have the best values of biological activity (IC50). An explanation is based on redox mechanism of action of nitrocompounds. NBO (Natural Bond Orbital) charges and LUKO (Lowest Unoccupied Kohn-Sham Orbitals) analysis at the ortho-nitro group are in agreement with these analyses. Considering quantum calculations and structural observations, four descriptors were selected a priori and submitted to a QSAR study using PLS (Partial Least Squares) and MLR (Multiple Linear Regression) modeling. A second QSAR approach was made from the another set of descriptors obtained through the online platform E-DRAGON, which were submitted to a variable selection method. The quality parameters obtained for models indicate that both are robust and predictive. / Os Adutos de Morita-Baylis-Hillman (AMBH) compreendem uma classe de moléculas investigadas por nosso grupo de pesquisas nos aspectos sintéticos, teóricos e de bioatividade. Neste trabalho, apresentamos modelos de Relação Quantitativa entre a Estrutura Química e a Atividade Leishmanicida (QSAR) envolvendo 32 AMBH aromáticos. Deste modo, inicialmente foram investigadas as conformações mais estáveis de cada composto através de métodos teóricos, as quais foram utilizadas na construção dos modelos. Foram obtidas curvas de energia potencial utilizando o método semi-empírico AM1, considerando graus de liberdade rotacionais (ligações sigma). A partir destas curvas, a conformação de menor energia para cada molécula foi selecionada e otimizada ao nível B3LYP/6-31+G(d), considerando os efeitos do solvente aquoso usando PCM ( Polarizable Continuum Model ). Dados espectroscópicos de Ressonância Magnética Nuclear de prótons corroboraram o estudo conformacional. Ligações de Hidrogênio Intramoleculares (LHI) se mostraram presentes na maioria das moléculas estudadas, conforme caracterização estrutural e cálculos QTAIM ( Quantum Theory Atoms in Molecules ). Curiosamente, os compostos que apresentaram Ligações de Hidrogênio envolvendo o grupo nitro (NO2) e a hidroxila (OH) possuem melhores valores de atividade biológica (menor IC50). Uma explicação está baseada no mecanismo de ação redox de nitrocompostos. Observação das cargas NBO ( Natural Bond Orbitals ) e análise dos orbitais de fronteira LUKO ( Lowest Unoccupied Kohn-Sham Orbitals ) ao nível do grupo orto-nitro estão de acordo com estas análises. Considerando os cálculos quânticos, bem como observações estruturais, quatro descritores foram selecionados a priori e submetidos a um estudo QSAR ( Quantitative Structure- Activity Relationships ) utilizando modelagem PLS ( Partial Least Squares ) e MLR ( Multiple Linear Regression ). Uma segunda abordagem QSAR foi realizada a partir de outro conjunto de descritores obtidos através da plataforma online E-DRAGON, os quais foram submetidos ao método de seleção de variáveis OPS ( Ordered Predictor Selection ). Os parâmetros de qualidade obtidos para os modelos indicam que ambos são robustos e preditivos.

Orientador: Fernando Antonio Santos Coelho / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-25T19:30:44Z (GMT). No. of bitstreams: 1 SouzaFilho_LuisGustavode1974-_D.pdf: 8902904 bytes, checksum: 85fa958ae1d753dea72d1d460737db4e (MD5) Previous issue date: 2014 / Resumo: Neste trabalho descrevemos uma nova abordagem para a síntese de ciclopentenonas substituídas com potencial atividade anti-inflamatória. As ciclopentenonas desempenham diversas atividades biológicas, a saber: anti-inflamatória, antineoplásica e antiviral. Devido a sua importância biológica sintetizamos várias ciclopentenonas utilizando adutos de Morita-Baylis-Hillman, como substrato. A sequencia se baseou no uso de uma reação de adição 1,4 catalisada por ródio, com adutos de Morita-Baylis-Hillman, levando à formação de cinamatos alfa-substituídos com elevada estereosseletividade E. A partir desses últimos, uma sequencia de etapas permitiu a preparação de 4 diferentes ciclopentenonas, em 7 etapas, com rendimentos globais variando de 10 a 30%. As ciclopentenonas sintetizadas tiveram seu perfil anti-inflamatório avaliado em modelos experimentais de inflamação não alérgica, edema de pata e peritonite ¿ in vivo e ensaio de agregação plaquetária ¿ in vitro. Demonstramos, através de tais experimentos, que essas ciclopentenonas inibem o processo inflamatório, ou seja, reduzem do edema de pata e a migração celular para a cavidade abdominal, além de uma possível indicação do mecanismo de ação dessas moléculas sobre a isoenzima ciclooxigenase tipo 2 (COX-2). Os ensaios de agregação plaquetária nos permitiram propor que o mecanísmo de ação possa ser por inibição de COX-2, já que tais ensaios mostraram que essas moléculas não inibem a enzima COX-1. Esse é o primeiro trabalho descrevendo a síntese de ciclopentenonas substituídas a partir de adutos de Morita-Baylis-Hillman / Abstract: This paper describes a new approach for the synthesis of substituted cyclopentenones with potential anti-inflammatory activity. The cyclopentenones play diverse biological activities, namely: anti-inflammatory, anticancer and antiviral. Due to their biological importance synthesize various cyclopentenones using Morita-Baylis-Hillman as substrate. The sequence was based on the use of a 1,4 addition reaction catalyzed by rhodium, with Morita-Baylis-Hillman, leading to the formation of alpha-substituted cinnamates with high stereoselectivity E. From the latter, a sequence of steps allowed the preparation of 4 different cyclopentenones in 7 steps with overall yields ranging from 10 to 30%. The cyclopentenones synthesized had their anti-inflammatory profile assessed in experimental models of non-allergic inflammation, paw edema and peritonitis ¿ in vivo and test platelet aggregation - in vitro. Demonstrated through such experiments , these cyclopentenones inhibit the inflammatory process, ie , reduce paw edema and cell migration into the abdominal cavity, as well as a possible indication of the mechanism of action of these molecules on the isoenzyme cyclooxygenase type 2 (COX-2). The platelet aggregation assays allowed us to propose that the mechanism of action may be through inhibition of COX - 2, since these trials have shown that these molecules do not inhibit COX-1 enzyme. This is the first paper describing the synthesis of substituted cyclopentenones from Morita-Baylis-Hillman adducts / Doutorado / Quimica Organica / Doutor em Ciências

Orientador: Fernando Antônio Santos Coelho / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-20T04:45:55Z (GMT). No. of bitstreams: 1 Santos_MariliaSimaodos_M.pdf: 8319783 bytes, checksum: b09561f94bf536402f8e5e21e0e6dc3c (MD5) Previous issue date: 2012 / Resumo: A potenciabilidade sintética dos adutos de Morita-Baylis-Hillman foi explorada no desenvolvimento de uma nova estratégia para a preparação de compostos tricarbonilados vicinais e derivados ciclopenta[b]indólicos. Os compostos tricarbonilados vicinais representam um padrão estrutural de grande interesse sintético, pois são empregados na síntese de heterociclos e diversas moléculas com atividade biológica. A metodologia desenvolvida envolve três etapas que constituem na síntese do aduto de MBH e de duas oxidações subsequentes. A rota se mostrou rápida, simples e eficiente, com rendimentos globais variando entre 15-75%. Além da facilidade operacional essa estratégia é quimicamente sustentável já que apresenta um baixo nível de geração de resíduos químicos. Os núcleos ciclopenta[b]indólicos estão presentes na estrutura de diversos produtos naturais e moléculas bioativas, fato que se torna um estímulo para o desenvolvimento de novas rotas sintéticas. A estratégia baseia-se na oxidação do aduto de MBH seguida de adição de Michael utilizando indol. O produto gerado sofre redução e em seguida é ciclizado em meio ácido levando à obtenção do núcleo de interesse. A síntese se mostrou altamente diastereosseletiva e o mecanismo da etapa de ciclização foi investigado através de espectrometria de massas. Os compostos foram avaliados contra algumas linhagens de células tumorais exibindo atividade citótóxica promissora / Abstract: The synthetic potential of Morita-Baylis-Hillman adducts was exploited towards the development of a new strategy for the preparation of vicinal tricarbonyl compounds and cyclopenta [b] indole derivatives. The vicinal tricarbonyl compounds represent a structural pattern of great synthetic interest because they are employed in the synthesis of heterocycles and several biologically active compounds. The three steps methodology involves the the preparation of MBH adducts, followed by two subsequent oxidations. The route proved to be fast, simple and efficient, with overall yields ranging from 15 to 75%. This strategy is operationally ease and sustainable, since a low level of waste is generated. The nuclei cyclopenta [b]indoles are present in the structure of some natural products and bioactive compounds. This has stimulated efforts towards the development of new synthetic routes to prepare this heterocyclic pattern. Our strategy is based on the oxidation of MBH adduct followed by Michael addition using indole as nucleophile to provide a substituted b-ketoester. The keto carbonyl was reduced and the substituted b-hydroxyester was therefore cyclized in acid conditions leading the desired heterocycles. The synthesis was highly diastereoselectivity and mechanism of the cyclization step was monitored by mass spectrometry. The compounds were evaluated against some tumor cell lines exhibiting promising cytotoxic activity / Mestrado / Quimica Organica / Mestra em Química

Orientadores: Marcos Nogueira Eberlin, Fernando Antonio Santos Coelho / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-26T16:01:36Z (GMT). No. of bitstreams: 1 Galaverna_RenanSouza_M.pdf: 4687299 bytes, checksum: d06d242cdf07c9f8f7f1abfb050e76ba (MD5) Previous issue date: 2014 / Resumo: Essa dissertação de Mestrado visa estudar o mecanismo da reação de Morita-Baylis-Hillman (MBH) em três versões (Clássica, Aza e Assimétrica) utilizando a técnica de espectrometria de massas com ionização por eletrospray (ESI-MS). Para o monitoramento mecanístico das versões clássica e Aza (MBH/Aza-MBH) foi introduzida uma nova abordagem, que é a utilização de reagentes marcados com etiquetas de carga (líquidos iônicos), a fim de facilitar a detecção dos intermediários e maximizar a aquisição de dados obtidos pelo monitoramento destas reações. Entre os reagentes de partida, (eletrófilo, catalisador e alceno ativado) o alceno ativado foi o reagente marcado, utilizou-se o íon metil imidazólio como etiqueta de carga. Além do uso de um reagente marcado, ambas as versões foram monitoradas utilizando reagentes neutros, com o propósito de avaliar em nível de comparação as metodologias abordadas, marcada e não-marcada. Para versão assimétrica da reação de MBH, foram utilizadas duas aminas hidroxiladas quirais derivadas de alcalóides cinchona, quinidina e ?-isocupreidina. O monitoramento mecanístico da versão assimétrica foi realizado utilizando um espectrômetro de massas com mobilidade iônica IM-MS. O tipo de mobilidade utilizada nesse estudo foi a Traveling Wave, comercialmente conhecida como TWIM-MS (Traveling Wave Ion Mobility Mass Spectrometry). A utilização desta possibilitou a separação e caracterização de intermediários estereoisoméricos formados no percurso da reação. Cálculos teóricos dos estados de transição para formação desses intermediários foram realizados a fim de suportar os dados obtidos por TWIM-MS. A utilização de um reagente marcado no monitoramento completo da reação de MBH/Aza-MBH mostrou melhores resultados em relação à reação não-marcada. Intermediários não detectados pela metodologia não-marcada foram detectados e caracterizados pela metodologia marcada, além do fato que a intensidade desses intermediários foi maior quando comparado à versão não-marcada. Para versão assimétrica, os dados obtidos por TWIM-MS e cálculos teóricos possibilitaram um melhor entendimento acerca da enantiosseletividade da reação de MBH quando diferentes catalisadores quirais são utilizados / Abstract: This dissertation aims to study the mechanism of the Morita-Baylis-Hillman reaction in three versions (Classical, Aza and Asymmetric) using Electrospray Ionization Mass Spectrometry (ESI-MS). For the mechanistic monitoring of the classical and Aza versions (MBH/Aza-MBH) a new approach was introduced, that is the use of marked reagents with charge tag (ionic liquid) in order to facilitate the detection of the reaction intermediates and maximize the data acquisition when monitoring these reactions. Among the start material, (electrophile, catalyst and activated alkene) the activated alkene was the marked reagent, using imidazolium ion as charge tag. Besides the use of a marked reagent, both versions (MBH/Aza-MBH) were monitored using neutral reagents, in order to compare the methodologies used, with and without charge tag. For the asymmetric MBH reaction, were used two hidroxylated chiral amines derived from cinchona alkaloids, quinidine and ?-isocupreidine. The mechanistic monitoring of the asymmetric reaction was performed using an ion mobility mass spectrometry IM-MS. The type of mobility used in this study was "traveling wave", commercially known as TWIM-MS (Traveling Wave Ion Mobility Mass Spectrometry). Using this instrument was possible to separate and characterize stereoisomerics intermediates formed in the course of the reaction. Theoretical calculations of the transition states for the formation of these intermediates were performed in order to support the data obtained by TWIM-MS. The use of a marked reagent in complete monitoring of the MBH/Aza-MBH reaction showed better results than non-tag reaction. Intermediates not detected by the non-tag methodology were detected and characterized by the charge tag methodology, furthermore, the intensity of these intermediates were higher than non-tag reaction. For the asymmetric version, the data obtained by TWIM-MS and theoretical calculations enabled a better understanding of the enantioselectivity of the MBH reaction when different chiral catalysts are used / Mestrado / Quimica Organica / Mestre em Química

L’objet de cette thèse est l’étude des catégories singulières des k-algèbres associatives surun anneau commutatif k. On développe la théorie de Morita pour les catégories singulières. Plus précisément, on propose une définition d’équivalence singulière à la Morita avec niveau, qui généralise la notion d’équivalence stable à la Morita introduite par Michel Broué. On montre qu’une équivalence dérivée de type standard induit une équivalence singulière à la Morita avec niveau. La deuxième partie de cette thèse est l’étude de la cohomologie de Hochschild singulière HH_sg(A,A) c’est-à-dire, l’espace des morphismes de A vers A[i] dans la catégorie singulière Dsg(A Aop) pour tous les nombres entiers i. Similaire à la cohomologie de Hochschild HH_(A,A), on montre que la cohomologie de Hochschild singulière HH_sg(A,A) est une algèbre de Gerstenhaber et donne une interprétation pour le crochet de Lie sur HH_sg(A,A) du point de vue de la théorie de PROP. On peut associer un complexe de cochaînes, qu’on appelle complexe de cochaînes de Hochschild singulières, C_sg(A,A) qui calcule la cohomologie de Hochschild singulière HH_sg(A,A). Alors on étudie une structure algébrique supérieure (e.g. l’algèbre de B1) sur C_sg(A,A) et propose une version singulière d’une conjecture de Deligne. L’objet de la troisième partie de cette thèse est de montrer que la structure d’algèbre de Gerstenhaber sur la cohomologie de Hochschild singulière est invariante par équivalences dérivées et équivalences singulières à la Morita avec niveau. L’idée de cette démonstration est analogue à l’approche développée par Keller lorsqu’il démontre que la structure d’algèbre de Gerstenhaber sur la cohomologie de Hochschild est invariante par équivalences dérivées. Similaire à la démonstration par Keller, on réalise HH_sg(A,A) avec le crochet de Lie comme une algèbre de Lie graduée du groupe algébrique gradué associé au groupe de Picard singulière sgDPic(A). / In this thesis, we are concerned with some aspects of singular categories of unitalassociative k-algebras over a commutative ring k. First, we develop a Morita theory for singular categories. Analogous to the classical Morita theory, we propose a definition of singular equivalence of Morita type with level. This follows and generalizes a definition of stable equivalence of Morita type introduced by Michel Broué. A derived equivalence of standard type induces a singular equivalence of Morita type with level. Second, we study the Hom-space from A to A[i] in the singular category Dsg(AkAop) of the enveloping algebra AkAop, where A is an associative k-projective k-algebra and i is any integer. Recall that the i-th Hochschild cohomology group HHi(A,A) can be realized as the Hom-space from A to A[i] in the bounded derived category Db(A k Aop). From this motivation, we call HomDsg(AkAop)(A,A[i]) the i-th singular Hochschild cohomology group and denote this group by HHi sg(A,A). Analogous to the Hochschild cohomology ring HH_(A,A), we prove that there is a Gerstenhaber algebra structure on the singular Hochschild ring HH_sg(A,A) and provide an interpretation of the Lie bracket from the point of view of PROP theory. We also associate a cochain complex, which we call singular Hochschild cochain complex, C_sg(A,A) to the singular Hochschild cohomology. Thenwe study the higher algebraic structures (e.g. B1-algebra) on C_sg(A,A) and propose asingular version of the Deligne conjecture. Following Keller’s approach which was developed for derived equivalences, we establish the invariance of the Gerstenhaber algebra structure which we defined on the singular Hochschild cohomology under singular equivalence of Morita type with level. In this proof, we define the singular derived Picard group sgDPic(A) of an associative algebra A and develop what we call a singular infinitesimal deformation theory. Then we realize HH_sg(A,A) as the graded Lie algebra of the ‘graded algebraic group’ associated to sgDPic(A).

Background. Depression and anxiety are common and debilitating disorders, and at least one third of patients do not respond to available interventions. Morita Therapy, a Japanese psychological therapy which contrasts with established Western approaches, is currently untested in the UK and may represent a potentially effective alternative approach. Aim. To optimise and investigate the feasibility and acceptability of Morita Therapy as a treatment for depression and anxiety in the UK. Design. Three studies were undertaken in line with the MRC framework (2008) for complex interventions. Study One: scoping and systematic review to describe the extent, range and nature of Morita Therapy research activity reported in English. Study Two: intervention optimisation study, integrating literature synthesis with qualitative research, to develop the UK Morita Therapy outpatient protocol. Study Three: mixed methods feasibility study encompassing a pilot randomised controlled trial (RCT) and embedded qualitative interviews to prepare for a fully-powered RCT of Morita Therapy versus treatment as usual (TAU). Results. Study One: 66 papers meeting the inclusion criteria highlighted heterogeneity in the implementation of Morita Therapy, and an absence of both UK-based research and relevant unbiased RCTs. Study Two: a potentially deliverable and acceptable therapy protocol and tailored therapist training programme were developed for a UK population. Study Three: 68 participants were recruited and 94% retained at four month follow-up; 70.6% of Morita Therapy participants adhered to the minimum treatment dose, and 66.7% achieved remission in depressive symptoms (compared to 30.0% in TAU). Qualitative and mixed methods findings indicated that Morita Therapy was broadly acceptable to therapists and participants, and highlighted potential moderators of acceptability, treatment adherence and outcomes. Conclusions. Patients in the UK can accept the premise of Morita Therapy and find the approach beneficial. It is feasible to conduct a large-scale UK-based trial of Morita Therapy with minor modifications to the pilot trial protocols.

Let $\overline{R}$ be a finitely bordered Riemann surface, and let $\mathfrak{E}_\rho(\overline{R})$ be a flat matrix $PU_n(\mathbb{C})$-bundle over $\overline{R}$. Let $\Gamma_c(\overline{R}, \mathfrak{E}(\overline{R}))$ denote the $C^*$-algebra of continuous cross-sections of $\mathfrak{E}(\overline{R})$, and let $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$ denote the subalgebra consisting of the continuous holomorphic sections, i.e.~the continuous cross-sections that are holomorphic on the interior of $\overline{R}$. The algebra $\Gamma_c(\overline{R}, \mathfrak{E}(\overline{R}))$ is an example of an $n$-homogeneous $C^*$-algebra, and the subalgebra $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$ is the principal object of study of this thesis. The algebras $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$ appeared in the earlier works \cite{Abrahamse1976} and \cite{Blecher2000}. Operators that can be viewed as elements in $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$ are the subject of \cite{Abrahamse1976}. The Morita theory of $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$, under the guise of a fixed-point algebra and in the special case of an annulus $R$, is studied in \cite[Ex.~8.3]{Blecher2000}. This thesis studies these algebras and their topological data $\mathfrak{E}_\rho(\overline{R})$ motivated by several problems in the theory of nonselfadjoint operator algebras. Boundary representations are an invariant of operator algebras that were introduced by Arveson in 1969. However, it took nearly 50 years to show that boundary representations existed in sufficient abundance in all cases. I show that every boundary representation of $\Gamma_c(\overline{R}, \mathfrak{E}(\overline{R}))$ for $\Gamma_h(\overline{R}, \mathfrak{E}(\overline{R}))$ is given by evaluation at some point $r \in \partial R$. As a corollary, the $C^*$-envelope of $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$ is $\Gamma_c(\partial R, \mathfrak{E}(\partial R))$. Using the $C^*$-envelope, I show that for certain choices of fibre and base space, $\Gamma_h(\overline{R}, \mathfrak{E}_\rho(\overline{R}))$ is not completely isometrically isomorphic to $A(\overline{R})\otimes M_n(\mathbb{C})$ unless the representation $\rho$ is the trivial representation. I also show that $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$ is an Azumaya over its center. Azumaya algebras are the ``pure-algebra'' analogues to $n$-homogeneous $C^*$-algebras \cite{Artin1969}. Thus the structure of the nonselfadjoint subalgebra $\Gamma_h(\overline{R},\mathfrak{E}(\overline{R}))$ reflects some of the structure of its $C^*$-envelope (which is $n$-homogeneous). Finally, I answer a question raised in \cite[Ex.~8.3]{Blecher2000} on the $cb$ and strong Morita theory of $\Gamma_h(\overline{R},\mathfrak{E}_\rho(\overline{R}))$, showing in particular that $\Gamma_h(\overline{R},\mathfrak{E}_\rho(\overline{R}))$ is $cb$ Morita equivalent to its center $A(\overline{R})$. As suggested in \cite[Ex.~8.3]{Blecher2000}, I provide additional evidence that $\Gamma_h(\overline{R},\mathfrak{E}_\rho(\overline{R}))$ may not be strongly Morita equivalent to its center. This evidence, in turn, suggests that there may be a Brauer group -like analysis for these algebras.

Morita Baylis-Hillman (MBH) reaction a carbon-carbon bond forming reaction between an α,β-unsaturated carbonyl and aldehydes or activated ketones in the presence of a nucleophilic catalyst. The MBH reaction is an atom-economical method of rapid increase of molecular complexity. The development of this process has received considerable attention in recent years. This dissertation presents the development of a new catalytic system for the symmetric and asymmetric MBH reaction. The new system for the racemic version of this reaction was accomplished employing a 1:1:1 ratio of catalytic amounts (10 mol%) of MgI2, TMEDA and DMAP and proved to be highly effective. For the asymmetric version was developed a highly enantio-selective system based on Fu’s planar chiral DMAP derivative (II) with ee´s up to 98%. Abnormal MBH adducts are obtained employing either ethyl 2,3-butadienoate or ethyl propiolate in good yields, in the presence if MgI2 and either a tertiary amine or phosphine as the nucleophile. The α,β-unsaturated carbonyls where prepared by a modified direct α- methylenation using paraformaldehyde, diisopropylammonium trifluoroacetate, and catalytic acid or base with excellent yields for several carbonyls compounds. The Negishi cross-coupling reaction is the Pd or Ni-catalyzed stereoselective cross-coupling or organozincs and aryl-, alkenyl-, or alkynyl halides. Enantioselective Negishi cross-coupling of aryl zincs and α-bromo ketones was accomplished employing a NCN Pincer complex as the catalyst with ee´s up 99%. The required pincer complexes have been prepared by the oxidative addition of pincer ligands with palladium or nickel. Additionally, It has been developed a direct and highly active, (NCN)-Pd catalytic system for the α-arylation of ketones with a variety of aryl bromides using the air and moisture stable [t-BuPheBox-Me2]PdBr (XVI) as the catalyst. The adducts are obtained in excellent yields (92% average for 20 examples) in only 1 hour using 1 mol% of catalyst loading. Perhaps more importantly, the work described here shows that XVI is highly reactive, highly selective, even on substrates bearing challenging functional groups such alkenes.

Freiburg i. Br., Univ., Diss., 2006.