Synthèse stéréosélective de pipéridines et activation électrophile chimiosélective d’amides en présence de dérivés de la pyridine

L’importance des produits naturels dans le développement de nouveaux médicaments est indéniable. Malheureusement, l’isolation et la purification de ces produits de leurs sources naturelles procure normalement de très faibles quantités de molécules biologiquement actives. Ce problème a grandement limité l’accès à des études biologiques approfondies et/ou à une distribution sur une grande échelle du composé actif. Par exemple, la famille des pipéridines contient plusieurs composés bioactifs isolés de sources naturelles en très faible quantité (de l’ordre du milligramme). Pour pallier à ce problème, nous avons développé trois nouvelles approches synthétiques divergentes vers des pipéridines polysubstituées contenant une séquence d’activation/désaromatisation d’un sel de pyridinium chiral et énantioenrichi. La première approche vise la synthèse de pipéridines 2,5-disubstituées par l’utilisation d’une réaction d’arylation intermoléculaire sur des 1,2,3,4-tétrahydropyridines 2-substituées. Nous avons ensuite développé une méthode de synthèse d’indolizidines et de quinolizidines par l’utilisation d’amides secondaires. Cette deuxième approche permet ainsi la synthèse formelle d’alcaloïdes non-naturels à la suite d’une addition/cyclisation diastéréosélective et régiosélective sur un intermédiaire pyridinium commun. Finalement, nous avons développé une nouvelle approche pour la synthèse de pipéridines 2,6-disubstituées par l’utilisation d’une réaction de lithiation dirigée suivie d’un couplage croisé de Negishi ou d’un parachèvement avec un réactif électrophile. Le développement de transformations chimiosélectives et versatiles est un enjeu crucial et actuel pour les chimistes organiciens. Nous avons émis l’hypothèse qu’il serait possible d’appliquer le concept de chimiosélectivité à la fonctionnalisation d’amides, un des groupements le plus souvent rencontrés dans la structure des molécules naturelles. Dans le cadre précis de cette thèse, des transformations chimiosélectives ont été réalisées sur des amides secondaires fonctionnalisés. La méthode repose sur l’activation de la fonction carbonyle par l’anhydride triflique en présence d’une base faible. Dans un premier temps, l’amide ainsi activé a été réduit sélectivement en fonction imine, aldéhyde ou amine en présence d’hydrures peu nucléophiles. Alternativement, un nucléophile carboné a été employé afin de permettre la synthèse de cétones ou des cétimines. D’autre part, en combinant un amide et un dérivé de pyridine, une réaction de cyclisation/déshydratation permet d’obtenir les d’imidazo[1,5-a]pyridines polysubstituées. De plus, nous avons brièvement appliqué ces conditions d’activation au réarrangement interrompu de type Beckmann sur des cétoximes. Une nouvelle voie synthétique pour la synthèse d’iodures d’alcyne a finalement été développée en utilisant une réaction d’homologation/élimination en un seul pot à partir de bromures benzyliques et allyliques commercialement disponibles. La présente méthode se distincte des autres méthodes disponibles dans la littérature par la simplicité des procédures réactionnelles qui ont été optimisées afin d’être applicable sur grande échelle.

Aproximacions sintètiques per a la preparació estereoselectiva de noves quinolil i pirazolilglicines i per a la preparació en fase sòlida de llibreries de benzotiazoles, 1,2,4-triazines i benzimidazoles

El treball experimental que ha permès redactar la present Tesi Doctoral ha estat dividit en dues parts. A la primera part es presenten els resultats referents a la síntesi estereocontrolada de noves heteroarilglicines (quinolil i pirazolilglicines) a partir de cetones acetilèniques, substrats quirals que permeten accedir a l'esquelet de diferents heterocicles (quinolines i pirazoles), la posterior obtenció dels corresponents quinolil i pirazolil--aminoalcohols i les diferents metodologies d'oxidació per tal d'accedir a les corresponents quinolil i priazolilglicines objectiu. A la segona part d'aquesta memòria s'ha estudiat, en dissolució, l'habilitat del grup alquilsulfona com a grup sortint eficaç en reaccions d'ipso-substitució nucleofilica. El desenvolupament d'aquesta reacció ha servit de punt de partida per a la creació de llibreries d'heterocicles amb alta diversitat molecular i potencial interès biològic sobre fase sòlida.

Os filhos evangélicos do novo caldeirão do diabo: a conversão religiosa na penitenciária de alcaçuz

The theme of the research is inserted at a field of intersection between the Sociology of Religion and Sociology of Violence, having as the general objective study the sociological meaning of the conversion of prisoners that lives at the biggest prison (Prison of Alcaçuz) of Rio Grande do Norte to the evangelical churches. The research is justified, because Brazil shelter the fourth greater arrested population arrested of the world, with projections indicating that it can turn the greatest in 2034. Besides, this study about religious conversion of prisoners to the Social Sciences is too important, because is a theme little developed in Brazil and deserves attention, one time that as the arrested people as the evangelicals are in expansion in our country. Starting from the precedent observations, we guide ourselves by the following problematic of research: the religious practice in Alcaçuz presents a mere instrumental perspective, where the actions of prisoners converted was on purpose oriented to conquest material or symbolic privileges; or purely religious, where seek a moral renovation? To develop the work, the scientific methodology adopted was exploratory and explanatory, using the Goffman´s theory about total institutions and presentation of self, and Blumer´s doctrine relating to Symbolic Interacionism and the Story life method, besides considerations about evangelical religion. Having this theoretical basis, was accomplished the Field research, when were made interviews and applied questionnaires to 11 Jailer Agents, 31 prisoners, Director and Vice-Dictor (in November, 2011), the coordinator of social projects of the prison and the coordinator of evangelization at the prisons in Rio Grande do Norte. As results, it was seeing in Alcaçuz that the prisoners can be separated in two groups: the one of Pavilions and other one of the Medical Section. The Pavilions are branded for managerial and structural problems, where are found idle prisoners in collective cells and with a historical of escaping attempts, mutinies and murders. The Medical Section has some individual cells or destined for two people, besides few collective also, and the prisoners work and have a more disciplined behavior, there isn t escapes or rebellions and that, for these reasons end for have more confidence from the Administration. About the presence of evangelical prisoners, most are at Medical Section, where exist a specific place to the cults (what doesn t at Pavilions). At the end, the conclusion is that the prisoner that says himself evangelical in Alcaçuz, although can be seeing with distrust about your real conversion, he gets win a trust vote and until the opposite being demonstrated in other words, that he is not hiding himself behind the bible to divert the vigilance of Direction and practice disciplinary faults without make any suspicions, is treated with more respect and has more opportunities live at Medical Section; have work, that most of times is paid and guarantee the homologation of your payment of penalty with work, besides other benefits, diminishing his time in jail

A escola de ensino médio público noturno: uma conjuntura favorável ao protagonismo estudantil coletivo em contraposição ao protagonismo juvenil via empoderamento

Ce travail etude le protagonisme juvénile en école de enseignement sécondaire publique, avec emphase a l enseignement nocturne. Considere las médiations que determinent le paradigme du protagonisme juvénile defendu pour théoriciens pos modernes et documents de reforme de enseignement sécondaire brésilien. Montre que les explications sur le protagonisme juvénile font part d une conception de pouvoir juvenile, proposé pour organismes multilatérales avec la volonté de mobiliser les jeunes pauvres pour faire actions du combat a pauvreté dans les nations sur le point de développement, conjoncture auquel sont proposées théories et pratiques que viabilizent la subsistance des jeunes pauvres en situation de risque. Discute la question de pouvoir juvenile et indique que la proposition de le protagonisme juvénile via pouvoir ont une espace favorable dans le sphère du enseignement sécondaire, niveau de la plupart de jeunes. Montre que la défense de pouvoir juvenile occulte chances de actions étudiants collectifs que permetent une intervention sociopolitique au élève de enseignement sécondaire, qui ont selement une function de homologation. Propose une recherche de possibilités de incentifs a le protagonisme juvénile collectif ou protagonisme étudiant collectif, auquel le étudiant presente suggestions pour le planification et éxecution de activités didactique pédagogiques dans l`école publique de enseignement sécondaire. Defend que la gestion démocratique, avec emphase en procès participatif, c est la principal déterminacion pour le protagonisme étudiant collectif. Méthodiquement , considere las dimensions suivantes pour le protagonisme juvénile: a) configuration de protagonisme juvénile b) protagonisme juvénile dans perspective légal/institutionel ; c) enseignement sécondaire et protagonisme juvénile ; d) possibilité de construction de protagonisme étudiant collectif dans enseignement sécondaire nocturne en Rio Grande do Norte, état choisi pour recherche. Sistematize une technique de revision de litérature sur le thème et informations d une consultation de documents, au-delà de donné constants de Banc de donées de la recherche Le Enseignement Sécondaire Publique Nocturne :registre et analyse de expérience dans l état de Rio Grande do Norte. Conclusion : il faut contribuer pour débats sur la participation politique de les jeunes dans le enseignement sécondaire nocturne, en presentant possibilités reéles de protagonisme étudiant collectif ; opinions presentées pour élèves sont très importantes a une direction d un rôle académique fait pour institutions scolaires dans ce moment , parce que des étudiants sont correspondants a interlocuteurs privilégiés ; le élève peut et deut être consulté depuis le moment de élaboration jusqu a réalisation de activités scolaires ; bien que il y a des entraves et difficultés immanents au enseignement sécondaire publique nocturne, se forment noveaux espaces de démocratisation de idées

Chemoenzymatic Synthesis of alpha-Hydroxy-beta-methyl-gamma-hydroxy Esters: Role of the Keto-Enol Equilibrium To Control the Stereoselective Hydrogenation in a Key Step

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Reações de Etanol com CO/H2 na Presença do Sistema Catalítico Ru(acac)3/I-

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

OXIDES AS HETEROGENEOUS PROMOTERS FOR LIQUID-PHASE HYDROCARBONYLATION REACTIONS WITH IODOCARBONYLRUTHENIUM CATALYSTS

Basic or acid oxides, used as heterogeneous promoters of carbonylruthenium catalysts in liquid-phase hydrocarbonylation reactions on oxygenated substrates, strongly affect the activity and selectivity of the catalytic system. Concurrent or successive reactions of simple carbonylation, homologation, hydrogenation to hydrocarbons, and etherification take place to varying extents. Carbonylation and etherification are favored by acid oxides and homologation and hydrogenation by basic oxides. This behavior is related to the formation and stabilization by the oxides of H+ and H- hydridocarbonylruthenium catalytic species, whose relative concentrations in solution depend on the nature of the oxide. Heterogeneous oxides are easily separated and recycled from the reaction mixture. Their use simplifies the catalytic system and allows one to direct the catalytic process toward the target product.

De como a raposa encontrou a serra do sol: discurso, memória e identidades

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cooperative effects of H+ and H- hydrido carbonyl ruthenium derivatives; role of homogeneous and heterogeneous protonic and lewis acids in catalytic hydrocarbonylation reactions

The role played by H+ hydrido iodocarbonyl and H- hydrido carbonyl ruthenium catalysts in the different catalytic steps of hydroformylation and hydroesterification of olefins, and in the homologation of alcohols has been investigated. The H- hydrido carbonyl species are mainly involved in the activation of olefins and in the hydrogenation of the acyl intermediates to aldehydes and alcohols, whereas the H+ hydrido iodocarbonyl derivatives are involved in the activation of alcohols and other oxygenated substrates, and in their carbonylation to esters. The cooperation between the two species, possible under particular reaction conditions, results in an improvement of the selectivity towards homologation (carbonylation plus hydrogenation) products. Heterogeneous Lewis acid promoters, easily recyclable from the reaction mixture, have also been successfully used in the hydrocarbonylation of alcohols, resulting in an increase of the carbonylation and homologation products. A reaction pathway in agreement with the experimental results is discussed. © 1989.

Procedimento para homologação de sistemas ecoeficientes para obtenção de créditos de carbono

This paper deals with the homologation process for obtaining carbon credits through the Clean Development Mechanism (CDM), that regulates the greenhouse gases reductions under the rules of the Kyoto Protocol. The CDM evaluates projects through a project cycle, which begins with the preparation of the Project Design Document (PDD) until the project certification to receive Certified Emission Reductions (CERs), popularly known as carbon credits. This study analyzed the implementation of the system Burner Recorder System for Low Flows of Biogas (QRBBV), developed by Marcelino Junior & Godoy (2009), in an eco-friendly wastewater treatment mini-plant (miniEETERA), built at the site of UNESP - Guaratinguetá SP. The QRBBV system is low cost and high reliability, developed to burn the methane generated at sites of low and variable production of biogas, which is not economically justified their energy recovery. Currently, almost all wastewater generated at the site of the campus is being treated by miniEETERA and, as a result, the biogas originated by this activity is being released into the atmosphere. Therefore, the project activity aims to capture and burn the biogas generated by miniEETERA, reducing the negative effects caused by the methane emissions into the atmosphere and, thus, claim to receive carbon credits. This work aimed to demonstrate the project applicability under CDM through the study and preparation of the PDD, as well as an analysis of the entire project cycle required for homologation. The result of the work obtained an estimate of only 20 CERs per year and proved to be economically unviable for approval through the CDM, since the spending with the approval process would not be compensated with the sale of CERs, mainly due the low carbon price in the world market. From an environmental standpoint, the project is perfectly... (Complete abstract click electronic access below)

Procedimento para homologação de sistemas ecoeficientes para obtenção de créditos de carbono

This paper deals with the homologation process for obtaining carbon credits through the Clean Development Mechanism (CDM), that regulates the greenhouse gases reductions under the rules of the Kyoto Protocol. The CDM evaluates projects through a project cycle, which begins with the preparation of the Project Design Document (PDD) until the project certification to receive Certified Emission Reductions (CERs), popularly known as carbon credits. This study analyzed the implementation of the system Burner Recorder System for Low Flows of Biogas (QRBBV), developed by Marcelino Junior & Godoy (2009), in an eco-friendly wastewater treatment mini-plant (miniEETERA), built at the site of UNESP - Guaratinguetá SP. The QRBBV system is low cost and high reliability, developed to burn the methane generated at sites of low and variable production of biogas, which is not economically justified their energy recovery. Currently, almost all wastewater generated at the site of the campus is being treated by miniEETERA and, as a result, the biogas originated by this activity is being released into the atmosphere. Therefore, the project activity aims to capture and burn the biogas generated by miniEETERA, reducing the negative effects caused by the methane emissions into the atmosphere and, thus, claim to receive carbon credits. This work aimed to demonstrate the project applicability under CDM through the study and preparation of the PDD, as well as an analysis of the entire project cycle required for homologation. The result of the work obtained an estimate of only 20 CERs per year and proved to be economically unviable for approval through the CDM, since the spending with the approval process would not be compensated with the sale of CERs, mainly due the low carbon price in the world market. From an environmental standpoint, the project is perfectly... (Complete abstract click electronic access below)

Total synthesis of (-)-indolizidine 167B via an unusual Wolff rearrangement from an alpha,beta-unsaturated diazoketone

A concise synthesis of the (-)-indolizidine alkaloid 167B and two formal syntheses of (-)-indolizidine 209D and (-)-coniceine are described in just three steps from an alpha,beta-unsaturated diazoketone, via an unusual photochemical Wolff rearrangement. Preparation of the unsaturated diazoketone is straightforward from N-Cbz-prolinal and a 3-diazo-2-oxopropylphosphonate, employing a Horner-Wadsworth-Emmons reaction. The strategy should be feasible and easily adaptable to the synthesis of other indolizidine alkaloids and analogues. (C) 2011 Elsevier Ltd. All rights reserved.

Total Synthesis of (+)-trans-Trikentrin A

Several syntheses have already been reported for cis-trikentrins and herbindoles, which are indole alkaloids unsubstituted at the C2 and C3 positions that bear a trans-1,3-dimethylcyclopentyl unit. Herein, we describe the first asymmetric and stereoselective synthesis of the more challenging trans-trikentrin A as its naturally occurring isomer. Different approaches were investigated and the strategy of choice was a combination of an enzymatic kinetic resolution and a thallium(III)-mediated ring contraction. The antiproliferative activities of the natural product and related intermediates have been tested against human tumor cell lines, leading to the discovery of new compounds with potent antitumor activity.

Optimal Supervisory Control of Hybrid Vehicles

Hybrid vehicles (HV), comprising a conventional ICE-based powertrain and a secondary energy source, to be converted into mechanical power as well, represent a well-established alternative to substantially reduce both fuel consumption and tailpipe emissions of passenger cars. Several HV architectures are either being studied or already available on market, e.g. Mechanical, Electric, Hydraulic and Pneumatic Hybrid Vehicles. Among the others, Electric (HEV) and Mechanical (HSF-HV) parallel Hybrid configurations are examined throughout this Thesis. To fully exploit the HVs potential, an optimal choice of the hybrid components to be installed must be properly designed, while an effective Supervisory Control must be adopted to coordinate the way the different power sources are managed and how they interact. Real-time controllers can be derived starting from the obtained optimal benchmark results. However, the application of these powerful instruments require a simplified and yet reliable and accurate model of the hybrid vehicle system. This can be a complex task, especially when the complexity of the system grows, i.e. a HSF-HV system assessed in this Thesis. The first task of the following dissertation is to establish the optimal modeling approach for an innovative and promising mechanical hybrid vehicle architecture. It will be shown how the chosen modeling paradigm can affect the goodness and the amount of computational effort of the solution, using an optimization technique based on Dynamic Programming. The second goal concerns the control of pollutant emissions in a parallel Diesel-HEV. The emissions level obtained under real world driving conditions is substantially higher than the usual result obtained in a homologation cycle. For this reason, an on-line control strategy capable of guaranteeing the respect of the desired emissions level, while minimizing fuel consumption and avoiding excessive battery depletion is the target of the corresponding section of the Thesis.

la necesidad de un proceso de homologacion para los acuerdos de refinanciación en la ley española

En esta tesis doctoral he encontrado un enorme problema en la regulación de los Acuerdos de Refinanciación en la Ley Concursal. Impide el derecho de defensa de los acreedores y de cualquier otro interesado. Por ello en aplicación de la Ley Concursal Italiana (modelo elegido por el legislador español) los problemas serían solucionados. La solución la encontramos mediante la inserción del proceso de homologación de los Acuerdos de Refinanciación en la Ley Concursal Española.