This PhD thesis is focused on the development of novel catalysis with low-oxidation main group species, mainly based on the group 13 element gallium, a relatively abundant, inexpensive, and low-toxic metal. Gallium in its stable high-oxidation state ‘+III’ is a commonly used Lewis acid catalyst in organic synthesis. In contrast, gallium in its less stable low-oxidation state ‘+I’ is under-explored, but may display both acceptor and donor properties at a single site (ambiphilicity). Based on the hypothesis that potentially ambiphilic gallium(I) –oxidatively generated in situ from gallium(0) using a silver salt– may activate both basic and acidic reagents, various gallium(I)-catalyzed carbon–carbon bond formations have been developed. These include catalytic C–O and C–B bond activations of electrophiles (acetals and aminals) and pro-nucleophiles (allyl and allenyl boronates), respectively. Gallium(III) and other metal Lewis acids have proved to be ineffective. These results represent the first catalytic use of gallium(0) in organic synthesis and a rare example of gallium(I) catalysis. The identity of the gallium(I) catalyst and its regeneration have been confirmed by 71Ga NMR analysis, and a reactive allyl–Ga(I) intermediate has been detected for the first time. In combination with 11B NMR and HRMS analyses, an SN1 reaction mechanism has been proposed. Importantly, the potential for asymmetric gallium(I) catalysis has been demonstrated using a chiral silver co-catalyst (40% ee). This gallium(I) chemistry has proved to be applicable to the catalytic activation of other electrophiles, including ethers or aldehydes, and pro-nucleophiles such as boranes, silanes, or tin-based reagents. Finally, the potential of a related low-oxidation aluminium catalyst has been explored for C–C bond formation.

Made available in DSpace on 2015-07-13T12:10:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-23. Added 1 bitstream(s) on 2015-07-13T12:25:27Z : No. of bitstreams: 1 000825064_20160228.pdf: 307325 bytes, checksum: 19ac282fd1189c52ae2046a9f1acbd26 (MD5) Bitstreams deleted on 2016-02-29T12:16:24Z: 000825064_20160228.pdf,. Added 1 bitstream(s) on 2016-02-29T12:17:23Z : No. of bitstreams: 1 000825064.pdf: 6733720 bytes, checksum: 484cdda7e2b141896c1f3c18d4742888 (MD5) / Os biocatalisadores (enzimas e/ou micro-organismos) são amplamente utilizados na síntese de moléculas bioativas, em especial os fármacos, para gerar ou resolver centros quirais. O levetiracetam, comercialmente conhecido como Keppra®, é um composto quiral com propriedades anticonvulsivantes cuja atividade farmacológica está relacionada ao enantiômero (S). O aumento da opção pelo uso do levetiracetam em detrimento a outros fármacos anticonvulsivantes está intimamente associado à baixa ocorrência de efeitos colaterais provocados por este. Diversas rotas quimiossintéticas para sua produção são relatadas na literatura. A maioria delas envolve um elevado número de etapas, alto consumo energético, uso de catalisadores metálicos e baixos rendimentos globais. Em contrapartida, este projeto teve por objetivo empregar uma rota quimioenzimática, com menor número de etapas, condições mais brandas e ambientalmente amigáveis de reação para a síntese do levetiracetam e análogos (série alifática). A respectiva série aromática também foi sintetizada, uma vez que trata-se de blocos construtores quirais para a síntese de compostos com reconhecida atividade anti-malária. A primeira etapa consistiu na síntese das cianidrinas racêmicas seguida da substiuição da hidroxila destas por heterociclos nitrogenados. Uma coleção de enzimas do tipo nitrila hidratases (E.C. 4.2.1.84) foi empregada para catalisar a conversão das nitrilas α-substituidas por N-heterociclos nas respectivas amidas quirais. As enzimas foram utilizadas tanto na forma isolada (obtidas comercialmente) quanto em células íntegras de bactérias e leveduras da Coleção de Micro-organismos do Laboratório de Biocatálise do IQ-UNESP Araraquara. As reações enzimáticas foram conduzidas em meio aquoso tamponado e em sistemas binários líquido iônico : solução tampão (10, 20, 40 e 80%) a fim de avaliar a influência do... / Biocatalysts (enzymes and/or microorganisms) are widely used in the synthesis of bioactive molecules, in particular pharmaceuticals, to generate or resolve chiral centers. Levetiracetam, commercially known as Keppra®, is a chiral compound with anticonvulsant properties whose pharmacological activity is related to the (S)-enantiomer. The increase in option for the use of levetiracetam over the others anticonvulsant drugs is closely associated with low incidence of side effects caused by this. Several chemosynthetic routes for its production are reported in the literature. Most of them involve numerous synthetic steps, high energy consumption, use of metal catalysts and low overall yields. On the other hand, this project aims to develop a chemoenzymatic route, with fewer steps, milder conditions and environmentally friendly reaction for the synthesis of levetiracetam and analogues (aliphatic series). The respective aromatic series was also synthesized, since it is chiral building blocks for the synthesis of compounds with known antimalarial activity. The first step was the synthesis of racemic cyanohydrin followed by substitution of the hydroxyl group by nitrogen heterocycles. Collections of nitrile hydratase enzymes type (EC 4.2.1.84) were used to catalyze the conversion of N-heterocycles α-substituted nitriles in the respective chiral amides. The enzymes were used both in isolated form (obtained commercially) as in whole cells bacteria and yeast Collection of Microorganisms of Biocatalysis Laboratory of IQ-UNESP Araraquara. The enzymatic reactions were performed in buffered aqueous medium and ionic liquid : buffer (10, 20, 40 and 80%) binary systems in order to evaluate the influence of the solvent on the enantioselectivity and yield of these reactions. The ionic liquids synthesized and used in this work were 1-butyl-3-methylimidazolium tetrafluoroborate, 1-butyl-3-methylimidazolium...

A assimetria nas preferências dos Bancos Centrais é um assunto que vem sendo muito discutido no meio acadêmico, mas até o momento essa polêmica tem se restringido a economias desenvolvidas como a canadense e inglesa. O que o texto a seguir se propõe é, em parte, tentar trazer essa discussão para o campo dos países emergentes, tomando como centro da análise a economia brasileira. Preferências assimétricas consistem num comportamento por parte da autoridade monetária que atribui perdas diferentes a desvios da taxa de inflação observada em relação à meta definida, que embora sejam de mesma magnitude apresentam sinais opostos. Replicando os testes já usados em outros estudos, o regime de Metas de Inflação é aqui abordado, iniciando sua análise sob uma ótica mais geral e depois o particularizando para a economia brasileira, desde sua concepção (em 1999 após a crise cambial de janeiro desse ano) até os dias atuais. Este comportamento assimétrico parece, ainda, ocasionar um viés inflacionário diferente daquele proposto pelo modelo KPBG (Kydland-Prescott-Barro-Gordon) que surge da ambição do Banco Central em estabelecer uma taxa de desemprego que esteja abaixo da taxa natural, num ambiente no qual as preferências, ao contrário do proposto, são quadráticas. Infelizmente, os dados brasileiros ainda não apontam na direção da assimetria, talvez por causa do tempo de implantação do regime no Brasil, talvez devido às turbulências que a economia brasileira sofreu decorrentes de crises internacionais e de suas conseqüências sobre o desempenho da política de Metas de Inflação que gerou inúmeros insucessos. No entanto, o histórico de hiperinflações e sua influência sobre as expectativas e os comportamentos dos agentes econômicos nos faz suspeitar de que dentro em breve a assimetria será não só detectada em nossa economia como também será fruto de estudos para o desenho e direcionamento da política monetária. / Central Banks preferences asymmetry is a subject that has been discussed for quite some time in academic publications. However, such controversy has been restricted to developed economies, such as the English and Canadian ones, so far. The following text intends to bring about the discussion to emerging countries, using the brazilian economy as the focus of the analysis. Asymmetric preferences can be defined as a particular behaviour of the monetary authorities that weigh differently their losses concerning inflation deviations from its predetermined target that have the same magnitude but different signs. The main tests used in other studies have been repeated here and the inflation target regime is approached, initially from a broader outlook and then specifically to the brazilian case, ever since its conception in 1999 (after the exchange rate crash in the same year) to the present day. The asymmetric behaviour seems to cause an inflationary bias different from the one proposed by the KPBG model (Kydland-Prescott-Barro-Gordon) which derives from the Central Bank ambition to establish an unemployment rate lower than its natural rate, in an environment in which preferences are quadratic. Unfortunately, brazilian data do not suggest asymmetry yet, maybe because the inflation target regime has been installed for too little time, or because of all the turmoil in the brazilian economy in recent international crisis and their consequences on the regime performance, that has been usually compromised. Nevertheless, the history of hyperinflations and their impacts on expectations and the agents behaviour raises suspicions that soon not only will asymmetry be found in our economy but it will also be studied to design monetary policy directives.

abstract: The need for multi-core architectural trends was realized in the desktop computing domain fairly long back. This trend is also beginning to be seen in the deeply embedded systems such as automotive and avionics industry owing to ever increasing demands in terms of sheer computational bandwidth, responsiveness, reliability and power consumption constraints. The adoption of such multi-core architectures in safety critical systems is often met with resistance owing to the overhead in migration of the existing stable code base to the new system setup, typically requiring extensive re-design. This also brings about the need for exhaustive testing and validation that goes hand in hand with such a migration, especially in safety critical real-time systems. This project highlights the steps to develop an asymmetric multiprocessing variant of Micrium µC/OS-II real-time operating system suited for a multi-core system. This RTOS variant also supports multi-core synchronization, shared memory management and multi-core messaging queues. Since such specialized embedded systems are usually developed by system designers focused more so on the functionality than on the coding standards, the adoption of automatic production code generation tools, such as SIMULINK's Embedded Coder, is increasingly becoming the industry norm. Such tools are capable of producing robust, industry compliant code with very little roll out time. This project documents the process of extending SIMULINK's automatic code generation tool for the AMP variant of µC/OS-II on Freescale's MPC5675K, dual-core Microcontroller Unit. This includes code generation from task based models and multi-rate models. Apart from this, it also de-scribes the development of additional software tools to allow semantically consistent communication between task on the same kernel and those across the kernels. / Dissertation/Thesis / Masters Thesis Computer Science 2014

A assimetria nas preferências dos Bancos Centrais é um assunto que vem sendo muito discutido no meio acadêmico, mas até o momento essa polêmica tem se restringido a economias desenvolvidas como a canadense e inglesa. O que o texto a seguir se propõe é, em parte, tentar trazer essa discussão para o campo dos países emergentes, tomando como centro da análise a economia brasileira. Preferências assimétricas consistem num comportamento por parte da autoridade monetária que atribui perdas diferentes a desvios da taxa de inflação observada em relação à meta definida, que embora sejam de mesma magnitude apresentam sinais opostos. Replicando os testes já usados em outros estudos, o regime de Metas de Inflação é aqui abordado, iniciando sua análise sob uma ótica mais geral e depois o particularizando para a economia brasileira, desde sua concepção (em 1999 após a crise cambial de janeiro desse ano) até os dias atuais. Este comportamento assimétrico parece, ainda, ocasionar um viés inflacionário diferente daquele proposto pelo modelo KPBG (Kydland-Prescott-Barro-Gordon) que surge da ambição do Banco Central em estabelecer uma taxa de desemprego que esteja abaixo da taxa natural, num ambiente no qual as preferências, ao contrário do proposto, são quadráticas. Infelizmente, os dados brasileiros ainda não apontam na direção da assimetria, talvez por causa do tempo de implantação do regime no Brasil, talvez devido às turbulências que a economia brasileira sofreu decorrentes de crises internacionais e de suas conseqüências sobre o desempenho da política de Metas de Inflação que gerou inúmeros insucessos. No entanto, o histórico de hiperinflações e sua influência sobre as expectativas e os comportamentos dos agentes econômicos nos faz suspeitar de que dentro em breve a assimetria será não só detectada em nossa economia como também será fruto de estudos para o desenho e direcionamento da política monetária. / Central Banks preferences asymmetry is a subject that has been discussed for quite some time in academic publications. However, such controversy has been restricted to developed economies, such as the English and Canadian ones, so far. The following text intends to bring about the discussion to emerging countries, using the brazilian economy as the focus of the analysis. Asymmetric preferences can be defined as a particular behaviour of the monetary authorities that weigh differently their losses concerning inflation deviations from its predetermined target that have the same magnitude but different signs. The main tests used in other studies have been repeated here and the inflation target regime is approached, initially from a broader outlook and then specifically to the brazilian case, ever since its conception in 1999 (after the exchange rate crash in the same year) to the present day. The asymmetric behaviour seems to cause an inflationary bias different from the one proposed by the KPBG model (Kydland-Prescott-Barro-Gordon) which derives from the Central Bank ambition to establish an unemployment rate lower than its natural rate, in an environment in which preferences are quadratic. Unfortunately, brazilian data do not suggest asymmetry yet, maybe because the inflation target regime has been installed for too little time, or because of all the turmoil in the brazilian economy in recent international crisis and their consequences on the regime performance, that has been usually compromised. Nevertheless, the history of hyperinflations and their impacts on expectations and the agents behaviour raises suspicions that soon not only will asymmetry be found in our economy but it will also be studied to design monetary policy directives.

Orientador: Luiz Carlos Dias / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Quimica / Made available in DSpace on 2018-08-06T22:02:57Z (GMT). No. of bitstreams: 1 SallesJunior_AirtonGoncalves_M.pdf: 2256633 bytes, checksum: 3fa984f2e156e431c4bffe35b6799992 (MD5) Previous issue date: 2006 / Resumo: Este trabalho relata a síntese assimétrica do fragmento C29-C39 do potente imunossupressor sangliferina A. O plano sintético utiliza como etapa-chave a reação aldólica com indução 1,5-anti entre a metil cetona 7.3 e o aldeído 31.3(S). A metil cetona 7.3 foi obtida a partir da amida de Weinreb 10.3 utilizando como etapas principais, reação de Horner-Wadsworth-Emmons, epoxidação régio- e diastereosseletiva e abertura de epóxido com cuprato de alta ordem. A amida 10.3 foi obtida a partir da reação aldólica entre N-propioniloxazolidinona 12.3 e a metacroleína mediada por titânio e hidroboração diastereosseletiva. O rendimento total para obtenção do fragmento C29-C39 foi de 18% para 16 etapas. / Abstract: This work describes the stereoselective synthesis of the C29-C39 fragment of the immunosuppressant sanglifehrin A. Our strategy involved a diastereoselective boron-mediated 1,5-anti aldol reaction of methyl ketone 7.3 with chiral aldehyde 31.3(S) as the key step.j Methyl ketone 7.3 is viewed as arising from Weinreb amide 10.3. Key steps in this approach are Horner-Waddsworth-Emmons homologation, selective epoxidation and epoxide ring opening with a higher order cuprate. The Weireb amide 10.3 is available from a titanium mediated aldol reaction of N-propionyloxazolidinone 12.3 with metacrolein followed by a diastereoselective hydroboration. This approach to the C29-C39 fragment of sanglifehrin A requires 16 steps and produced the desired molecule in 18% overall yield. / Mestrado / Quimica Organica / Mestre em Química

ÉTUDES VERS LA SYNTHESE TOTALE DE LA (+)-TAUTOMYCETINE: La (+)-tautomycétine (2 ,TTN), polycétide naturel isolé en 1989 à partir de souches de Streptomyces griseochromogenes possède, en plus de sa structure chimique unique, des activités biologiques prometteuses. Plus récemment, comme étant un inhibiteur spécifique des sérine/thréonine phosphatases de type 1 (PP1) et 2A (PP2A). Nous nous sommes intéressés au développement d'une voie de synthèse pour accéder à la (+)-tautomycétine. Nous avons réussi à synthétiser les deux fragments principaux de la tautomycétine, le fragment B2 correspondant à la partie C1-C12 et compos 260, qui constitue la partie C7'-C13. Ces deux fragments contiennent tous les carbones de la TTN. / STUDIES TOWARD THE TOTAL SYNTHESIS OF (+)-TAUTOMYCETIN: (+)-Tautomycetin is a polyketide natural product isolated in 1989 from Streptomyces griseochromogenes with antifungal activity. Currently, TTN is best known for its activity in serine/threonine phosphatase proteins. We developed a convergent synthetic route to this natural product. Two key fragments of (+)-tautomycetin were synthesized, the B2 fragment containing the C1-C12 chain and the compound 260, corresponding to the C7'-C13 fragment of (+)-tautomycetin. The synthesis of fragment B2 employed a stereoselective chiral epoxide opening reaction as a key step, which consist of a novel strategy to prepare the desoxypropionate moiety of TTN. The synthesis of 260 employed a novel method for bis-esterification of anhydrides developed in the Dias-Campagne groups

Efavirenz, a drug that is still inaccessible to millions of people worldwide, is potent non nucleoside reverse transcriptase inhibitor (NNRTI), is one of the preferred agents used in combination therapy for first-line treatment of the human immunodeficiency virus (HIV). NNRTIs attach to and block an HIV enzyme called reverse transcriptase, by blocking reverse transcriptase; NNRTIs prevent HIV from multiplying and can reduce the amount of HIV in the body. Efavirenz can't cure HIV/AIDS, but taken in combination with other HIV medicines (called an HIV regimen) every day helps people with HIV live longer healthier lives. Efavirenz also reduces the risk of HIV transmission and can be used by children who are suffering from HIV/AIDS. All the above therapeutic uses of efavirenz prompted us to identify the novel and hopefully cost efficient synthetic methodology for the preparation of efavirenz. In this thesis a new synthetic method for asymmetric synthesis of efavirenz is described. This route started from commercially available starting materials and it is first established in traditional batch chemistry and further the parameters transferred to a semi continuous flow protocol for optimization.

Several camphor and pinane derivatives have been synthesised and evaluated for use as chiral auxiliaries in asymmetric synthesis. Various blocking groups have been attached to the camphor skeleton in attempts to improve stereofacial selectivity; these include α-methoxybenzyl and xylyl groups, and novel stereoisomeric ketal moieties derived from meso- and (R,R)-(-)-2,3-butanediol. Benzylation reactions carried out on the lithium enolates of ester derivatives of the camphor-derived chiral auxiliaries afforded α-benzylated products in 5-60% diastereomeric excess. Stereochemical aspects have been explored using high resolution NMR, X-ray crystallographic and computer modelling techniques, and hydrolysis of selected α-benzylated products has permitted the diasteroselective bias to be confirmed. Opposite configurations at the new stereogenic centre are clearly favoured by the xylyl and ketal blocking groups - an observation rationalised in terms of the presence or absence of chelating potential in the blocking group. Baylis-Hillman reactions carried out on a series of specially prepared camphor-derived acrylic esters containing the ketal blocking group exhibited both low diastereoselectivities (0-30% d.e.) and very long reaction times. Chiral silyl enol ethers, synthesised using both pinane and camphor derivatives as chiral auxiliaries, showed up to 20% diastereomeric excess in MCPBA oxidation, alkylation and Mukaiyama reactions. Attempts to bring the prochiral centre in the silyl enol ether substrates closer to the chiral auxiliary, and thus improve the stereofacial selectivity, proved unsuccessful. The silyl enol ether derivatives, however, display interesting fragmentation patterns in their electron impact mass spectra, which were investigated using a combination of high resolution MS, comparative low resolution MS and metastable peak analysis.

No description available.