Reações biocatalíticas com compostos di-hidroxilados visando a obtenção de blocos de construção de moléculas bioativas

Abstract

In the present work, the development of biocatalytic methods aimed at the transformation of dihydroxylated compounds (dihydroxynaphthalenes and catechols) was addressed, with a focus on the regioselective and enantioselective synthesis of building blocks. These building blocks can be employed in the preparation of bioactive molecules. The biocatalytic applications of the enzymes lipases and (S)-norcoclaurine synthase were investigated, with an emphasis on medicinal chemistry. Through the use of lipases, it was possible to obtain regioselective monoesters of dihydroxynaphthalenes with yields ranging from 52–85% (A10–A17), and monoesters of catechols with yields of 53–82% (B14–B16). In addition, CAL-B lipase was used for the kinetic resolution of alcohol C2, resulting in 53% conversion and 89% enantiomeric excess. This result is promising for the synthesis of the drug (S)-rotigotine or related molecules, using commercially available lipases. Using the enzyme (S)-norcoclaurine synthase, a ninhydrin-based colorimetric method was developed to selectively quantify dopamine (a primary amine) over the reaction product (a secondary amine). This method is applicable to the determination of conversion in biocatalytic reactions catalyzed by (S)-norcoclaurine synthase and shows potential for automation in the screening of different substrates and conditions, with possible application to other enzymatic systems. Thus, the present work introduces and demonstrates chemoenzymatic methods for application in medicinal chemistry, focusing on dihydroxylated compounds.