Study of enzymatic reductions of alpha,beta-unsaturated ketones, and their applications in the preparation of compounds of synthetic interest

Abstract

In this project, we intend the synthesize prochiral alpha-chloroenones, alpha-bromoenones and alpha-methyleneketones that can be reduced to furnish chiral halohydrins, epoxides and alpha-methylketones of synthetic interest. We intend to investigate biocatalytic routes to produce these compounds in high yields and enantiomeric excesses. In the case of alpha-haloenones, we intend to study the application of microorganisms from Brazilian collections in their bioreduction to produce enantiomerically enriched halohydrins, which are precursors to epoxides used as synthetic intermediates. In the case of alpha-methyleneketones, in a first stage we will evaluate microorganisms for the chemo- and enantioselective reduction of the C=C bond, to produce enantiomerically enriched alpha-methylketones that are natural products or synthetic intermediates for their production. In a second stage, we intend to work at the research group Biocatalysis and Organic Chemistry at the Delft University of Technology (Delft, Netherlands), to investigate the potential of a variety of free enoate reductases (ERs) in the C=C bond reduction. In this stage, besides the activity and enantioselectivity, emphasis will be given to cofactor regeneration methods (including novel methodologies developed by this group at Delft). Among the motivations of this project, two of them stand out: the great synthetic interest of the target molecules, especially in the synthesis of natural products, and the development of novel and more sustainable methodologies for the production of these enantiomerically enriched compounds.