Studies of enzymatic reductions of activated alkenes

Author(s)

Bruno Ricardo Silva De Paula

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Química
• Defense date: 2015-09-21

Examining board members

Paulo José Samenho Moran; Paulo Mitsuo Imamura; Ronaldo Aloise Pilli; Maria da Graça do Nascimento; Leandro Helgueira Andrade

• Advisor: Paulo José Samenho Moran

Abstract

This project¿s main focus was the study of biocatalytic reductions of activated alkenes. In the first stage of this work reductions of structurally related enones were performed: the presence or absence of an allylic halogen in the substrate acted as a stereocontrol strategy for these hydrogenations. Thus, ketones with both (R) and (S) configurations could be obtained from different substrates using the same biocatalyst. In cases where the â-haloenones¿ benzylic carbocations were particularly stabilized, however, substrate solvolysis was the exclusive reaction, and no bioreduction was observed. To overcome this limitation, â-acetoxienones were synthesized and subjected to the same biotransformation conditions. These substrated showed the same stereochemical behavior as their â-halo counterparts, but did not undergo solvolysis, providing the bioreduction products evenin the cases of electron rich aromatic rings. This strategy was employed in the synthesis of both isomers of Tropional® from related enones bearing a methyl or acetoxymethyl group á to the carbonyl. In the next stage of this project, we performed biotransformations of enones bearing other leaving groups in allylic position. In particular, a â-azidoketone produced a mixture of reduction products: one with the azido group in the â position, and the other one without it. We found out that elimination of hydrazoic acid from the potential â-azidoketone intermediate was very slow, and did not justify the formation of the ketone without the azido group. Finally, biotransformations of miscellaneous activated alkenes were performed. We found out that the microorganisms used in this work were not successful in the reduction of á,â-unstaturated acid and esters, but one yeast was capable of reducing an á,â-unsaturated acylphosphonate. Unfortunately, due to competing hydrolysis to the corresponding acid, both the saturated and unsaturated acids were observed in the reaction medium. The same yeast was capable of reducing an á,â-unsaturated acylsilane. In the last stage of this work, we performed biotransformations of allylic alcohols, which produced the saturated alcohol or acid depending on the employed reaction conditions (AU)

• FAPESP's process: 12/08385-6 - Study of enzymatic reductions of alpha,beta-unsaturated ketones, and their applications in the preparation of compounds of synthetic interest
• Grantee: Bruno Ricardo Silva de Paula
• Support Opportunities: Scholarships in Brazil - Doctorate