Síntese quimioenzimática do Mesilato de Rasagilina (Azilect)

Detalhes bibliográficos
Ano de defesa: 2013
Autor(a) principal: Fonseca, Thiago de Sousa
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/14183
Resumo: Here we describe the synthesis of the chemoenzymatic Rasagilina mesylate (Azilect®), a drug used in monotherapy in patients with early stage Parkinson. One of the goals of this project was to carry out the introduction of chirality via biocatalysis processes. We studied two strategies: i) bioreduction of indanone in the presence of a series of yeast and ii) kinetic resolution of rac-indanol using lipases in organic solvent. In strategy (i) was conducted a screening with six yeasts. In all tests the (S)-indanol was obtained in low conversions (9.4 to 13.2%) and enantiomeric excesses of up to 97.6%. Due to low conversion rates, we decided to implement the strategy (ii). After screening of nine commercial lipases, was possible to verify that the Amano lipase AK from Pseudomonas fluorescens and Lipase from Thermomyces lanuginosus immobilized on immobead-150 were the most efficient in the kinetic resolution of rac- indanila acetate in aqueous medium with enantiomeric ratio equals 111.0 and 167.0 respectively. Thus, such lipases were selected for the kinetic resolution of rac-indanol in organic media. The best results of enzyme activity and selectivity were obtained using hexane as a solvent, reaction time of 15 minutes and 30ºC for Amano lipase AK (free enzyme) and 35ºC for Thermomyces lanuginosus, with enantiomeric ratio equals 200 for both cases. Were held assets of Amano AK (free enzyme) in various media and the best results were obtained selectivity and activity in hexane as organic solvent, reaction time of 6 hours and 30 º C using Amano Lipase AK immobilized chitosan in 2.5% low molecular weight; sodium alginate 2.5% and Amano AK lipase immobilized on chitosan 5.0% low molecular weight. The study was conducted reuse of immobilized lipase, Thermomyces lanuginosus being immobilized on immobead-150, the more efficiently compared to the others, since it has provided excellent results in higher reaction cycles. Subsequently, using a Mitsunobu reaction, (S)-indanol was converted to (R)-azidoindano with 70% yield. Then, the (R)-azidoindano was subjected to Staudinger reaction, producing (R)-indanamine in 60% yield.