Le travail présenté dans ce manuscrit concerne le développement d'une nouvelle voie d'accès à une famille de butyrolactames naturels à fort potentiel thérapeutique basé sur une réaction de cycloaddition [2+2] suivie d'une expansion de cycle. Dans la partie principale, une méthodologie permettant l'accès aux cyclobutanones hautement fonctionnalisées par cycloaddition [2+2] entre des éthers d'énols chiraux et divers cétènes fonctionnalisés a été développée. Avec cette méthodologie, diverses cyclobutanones ont pu être obtenues de façon hautement chimio-, régio- et stéréosélective. L'expansion de cycle sur les cyclobutanones préparées précédemment afin d'obtenir le squelette butyrolactame de la (–)-Salinosporamide A a ensuite été étudiée. La dernière partie de ce travail consiste en une étude de la réaction de cycloaddition [2+2] entre un cétène et un éther d'énol activée par un acide de Lewis présent en quantité catalytique. Cette première étude semble indiquer qu'une activation avec un acide de Lewis est possible lorsqu'un éther d'énol encombré est utilisé. / The work reported in this manuscript concerns the development of a new approach to a family of natural butyrolactames, with a high therapeutic potential, based on a [2+2] cycloaddition reaction followed by a ring expansion. In the main part, a procedure for the preparation of highly functionalized cyclobutanones by [2+2] cycloaddition between chiral enols ethers and functionalized ketenes has been developed. With this method, a variety of cyclobutanones were obtained in a highly chemo-, regio- and stéréosélective manner. The ring expansion of the previously prepared cyclobutanones to obtain the butyrolactame skeleton of (–)-Salinosporamide A was next investigated. The last part of this manuscript consists in a study of the [2+2] cycloaddition reaction between ketene and enol ether activated by a Lewis acid in catalytic amount. This first study seems to point out that an activation of [2+2] cycloaddition reaction is possible when a sterically hindered enol ether is used.

Made available in DSpace on 2015-03-05T18:57:21Z (GMT). No. of bitstreams: 0 Previous issue date: 29 / Nenhuma / Os ciclos econômicos representam as oscilações de variáveis como a produção e o emprego de um setor, região ou país. Apresentam-se de forma única, não divisível e com características próprias quanto à sua amplitude e duração. De uma forma geral, os ciclos podem ser subdivididos nas seguintes fases: expansão, crise e depressão. Cada fase alterna-se a outra predeterminando o comportamento da fase posterior. Uma das técnicas mais promissoras é o modelo de mudança de regime, com o trabalho seminal de Hamilton (1989), abriu-se um novo campo de investigação dentro do tema. Destaca-se que a investigação sobre ciclos econômicos na literatura internacional esteve focada nas economias centrais, e os países emergentes ainda apresentam um número relativamente baixo de trabalhos na área. Quando comparados a de outros continentes, esses apresentam um contexto singular para ser discutido em termos de teoria dos ciclos econômicos. Nesse estudo, foi utilizada a técnica de mudança de regime Markoviano, que além das formulações / Economic cycles represent fluctuations of variables such as production and employment in a sector, region or country. They are so unique, and not divisible with characteristics as to its magnitude and duration. In general, the cycles can be subdivided in the following phases: expansion, crisis and depression. Each phase switches to the behavior of other predetermined later. One of the most promising techniques is the model of regime change, with the seminal work of Hamilton (1989) opened up a new field of research within the theme. It is that research on economic cycles in the international literature has focused on central economies and emerging countries still have a relatively low number of jobs in the area. When compared to other continents, they have a natural context for discussions in terms of the theory of economic cycles. In this study, we used the technique of changing the Markovian regime, which in addition to univariate and multivariate formulations was tested bivariate arrangements. Because of th