Estudo da Síntese de Butanolídeos Bioativos por Meio da Reação de Morita-Baylis-Hillman, Uso de Meio Micelar para Acelerar a Reação de Morita-Baylis-Hillman e Reações de Tsuji-Trost Ambientalmente Responsáveis e Sustentáveis

Abstract

Natural butanolides are compounds that have a restricted occurrence, presenting a better prospection in plants of the family Lauraceae. Several reports in the literature account for relevant cytotoxic activities associated with butanolides extracted from plant tissue, however there are few reports on their total synthesis. Due to the low natural availability of butanolides, total synthesis becomes a valuable tool to enable large-scale production of butanolides of interest. Nevertheless, it raises concerns associated to modern organic synthesis: the environmental impact inherent to the laboratory practices. Hence, classical synthesis routes must be replaced by environmentally responsible routes. In order to meet this principle, the Morita-Baylis-Hillman (MBH) reaction is an excellent tool that can be applied in the synthesis of bioactive butanolides. Therefore, in the present work, a route for the total synthesis of butanolides was proposed, which exploited the MBH reaction as a fundamental step for the synthesis of bioactive butanolides. In Chapter I, the synthesis of activated alkenes, precursors of butanolides, was performed, and several attempts of C-C bonding between these intermediates and several aldehydes using the MBH reaction were presented. In view of the observed lack of reactivity of alkenes, a methodology of MBH reaction was developed using micellar nanoreactors, to investigate the hypothesis that the highly reactive environment inside the micelles could favor the planed reaction (Chapter II). In order to test other types of reaction using micellar nanoreactors, in Chapter III an environmentally responsible methodology for Tsuji-Trost reactions in water using low concentrations of palladium (Pd) was developed. It was concluded that the methodology developed in chapter II efficiently promoted the coupling between aldehydes and terminal activated alkenes, but the use of activated substituted alkenes did not provide the expected products, thus not allowing the synthetic route proposed in Chapter I to be continued. Finally, the studies presented in Chapter III show that a methodology that allows the use of only 0.1 mol% of Pd in Tsuji-Trost reactions could be successfully developed.