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

• Grant number: 12/08385-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: August 01, 2012
• End date: July 31, 2015
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Paulo José Samenho Moran
• Grantee: Bruno Ricardo Silva de Paula
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

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.

Scientific publications

(7)

(The scientific publications listed on this page originate from the Web of Science or SciELO databases. Their authors have cited FAPESP grant or fellowship project numbers awarded to Principal Investigators or Fellowship Recipients, whether or not they are among the authors. This information is collected automatically and retrieved directly from those bibliometric databases.)

DE PAULA, BRUNO R. S.; ZAMPIERI, DAVILA; RODRIGUES, J. AUGUSTO R.; MORAN, PAULO J. S.. Biotransformation of 3-azidomethy1-4-phenyl-3-buten-2-one and analogs by Saccharomyces cerevisiae: New evidence for an S(N)2 ` mechanism. TETRAHEDRON-ASYMMETRY, v. 28, n. 4, p. 545-549, APR 15 2017. (12/08385-6, 16/12074-7)

CARACELLI, IGNEZ; ZUKERMAN-SCHPECTOR, JULIO; MORAN, PAULO J. S.; DE PAULA, BRUNO R. S.; TIEKINK, EDWARD R. T.. Crystal structure of 7-[(2E)-2-benzylidene-3-oxobutoxy]-4-methyl-2H-chromen-2-one. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 71, n. 4, p. O222-U213, APR 2015. (12/08385-6)

DE PAULA, BRUNO R. S.; ZAMPIERI, DAVILA S.; NASARIO, FABIO D.; RODRIGUES, J. AUGUSTO R.; MORAN, PAULO J. S.. Regioselectivity Control of Enone Reduction Mediated by Aqueous Baker's Yeast with Addition of Ionic Liquid [bmim(PF6)]. BIOCATALYSIS AND AGRICULTURAL BIOTECHNOLOGY, v. 12, p. 166-171, OCT 2017. (12/08385-6, 14/00108-9)

DE PAULA, BRUNO R. S.; ZAMPIERI, DAVILA; RODRIGUES, J. AUGUSTO R.; MORAN, PAULO J. S.. Biotransformation of 3-azidomethy1-4-phenyl-3-buten-2-one and analogs by Saccharomyces cerevisiae: New evidence for an S(N)2 ' mechanism. TETRAHEDRON-ASYMMETRY, v. 28, n. 4, p. 5-pg., 2017-04-15. (12/08385-6, 16/12074-7)

PAULA, BRUNO R. S.; ZAMPIERI, DAVILA; RODRIGUES, J. AUGUSTO R.; MORANA, PAULO J. S.. Bioreduction of alpha-Acetoxymethyl Enones: Proposal for an S(N)2 ` Mechanism Catalyzed by Enereductase. ADVANCED SYNTHESIS & CATALYSIS, v. 358, n. 22, p. 3555-3571, NOV 17 2016. (12/08385-6, 14/00108-9)

CARACELLI, IGNEZ; ZUKERMAN-SCHPECTOR, JULIO; MORAN, PAULO J. S.; DE PAULA, BRUNO R. S.; TIEKINK, EDWARD R. T.. Crystal structure of 7-[(2E)-2-benzylidene-3-oxobutoxy]-4-methyl-2H-chromen-2-one. ACTA CRYSTALLOGRAPHICA SECTION E-CRYSTALLOGRAPHIC COMMUNICATIONS, v. 71, p. 13-pg., 2015-04-01. (12/08385-6)

PAULA, BRUNO R. S.; ZAMPIERI, DAVILA; RODRIGUES, J. AUGUSTO R.; MORANA, PAULO J. S.. Bioreduction of alpha-Acetoxymethyl Enones: Proposal for an S(N)2 ' Mechanism Catalyzed by Enereductase. ADVANCED SYNTHESIS & CATALYSIS, v. 358, n. 22, p. 17-pg., 2016-11-17. (12/08385-6, 14/00108-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

PAULA, Bruno Ricardo Silva de. Studies of enzymatic reductions of activated alkenes. 2015. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Química Campinas, SP.