Synthesis of 1,2,3-triazoles from enantioenriched intermediates by enzymatic kinetic resolution

Abstract

Enantiomerically pure compounds have importance mainly in the pharmaceutical area since different enantiomers can have different biological activities. Through the enzymatic kinetic resolution of racemates, biocatalysis is a promising alternative in the enantiomeric enrichment of chiral compounds through more sustainable routes, with lipases being the most explored enzymatic class. Therefore, this study aims to explore the synthesis of enantiomerically enriched compounds of the hydroxy-triazole type through chemo-enzymatic methodologies, since the 1,2,3-triazolyl nucleus is a known target for its efficiency in several biological applications. The first step of the work involves the synthesis of azidoketone-type compounds from commercial bromoketones, which will be subjected to reduction reactions to obtain the respective azidoalcohols. In a second step, an azidoalcohol (model compound) will be used in a screening process of commercial lipases in enzymatic kinetic resolutions involving the acetylation reaction. After finding the most promising lipase(s), some reaction variables will also be optimized. After developing the optimized reaction condition, all azidoalcohols will be submitted to the process of enzymatic kinetic resolution. In a third step, the enantioenriched azidoalcohols, in turn, will be used in the synthesis of hydroxy-triazoles using the 1,3-dipolar cycloaddition click reaction catalyzed by Cu(I). In a partnership with the research group NEQUIMED of the Instituto de Química de São Carlos, the antitumor properties of the compounds synthesized in this study will be evaluated. However, biological tests are not part of the project to be carried out by the undergraduate student.(AU)