Biorredução de compostos carbonílicos alfa,beta-insaturados visando à síntese de substâncias opticamente ativas

Abstract

SILVA, R. M. Bioreduction of α,β-unsaturated carbonyl compounds toward the synthesis of optically active substances. 2015. 162f. Dissertation (Master). Faculdade de Ciencias Farmaceuticas de Ribeirao Preto – Universidade de Sao Paulo, Ribeirao Preto, 2015. In recent years, the preparation of enantiomerically pure compounds has become a concern and a challenge to the industry. This fact is a consequence of the tenuous relationship between the spatial structure of substances and the different flavors, odors, pharmacokinetic and pharmacodynamic processes and toxicity that they play in the body. In this context, the asymmetric synthesis of α-alkyl substituted optically active carbonyl compounds has received great attention because they are important building blocks in the synthesis of chiral drugs and natural products. Thus, this study aimed to develop methodologies that allow the preparation of this enantiomerically pure compounds by controlling the formation of stereogenic centers using biocatalysis. To this end, various activated olefins substituted with electron withdrawing groups (carbonyl) were synthesized using two procedures, aldol condensation and esterification reactions. These α,β-unsaturated carbonyl compounds were obtained in good yields (48-94%) and subjected to the biocatalytic reduction mediated by whole cells of microorganisms. Initially, we used the olefin (E)-3-methyl-4-phenyl-3-buten-2-one (51a) as a model substrate for the optimization of the experimental conditions and determine wich one provide the product with better conversion and enantiomeric purity. In these tests, we evaluated various reaction parameters such as the composition of the reaction medium (aqueous, biphasic and buffer), the presence of additives (glucose and phase transfer catalyst), different microorganisms and adsorbing effect of using Amberlite XAD-7. Thus, the biorreduction in aqueous medium, without additives, mediated by LSC-II yeast and with the application of Amberlite XAD-7 was the reaction condition that presented the best enantiomeric excess (81%) and was selected for a methodological study that evaluated the steric and electronic effects of the substituents. It was observed that the substituent in the βposition of the aryl group, the size increase of the α-substituent and the presence of an ester group had an important role in the stereoselectivity of the reaction. Finally, application of the methodology on muguesia enantioselective synthesis, a floral fragrance, was evaluated. The results obtained showed the high potential of the methodology in chemoselective bioreduction of α,β-unsaturated carbonyl compounds and preparation of optically active substances.