Asymmetric photocatalysis applied to the synthesis of Brivaracetam: synthetic approaches employing enabling technologies for chemical synthesis

• Grant number: 19/27176-8
• Support Opportunities: Regular Research Grants
• Start date: October 01, 2020
• End date: September 30, 2022
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Agreement: Foundation for Research and Innovation of the State of Santa Catarina (FAPESC)
• Principal Investigator: Kleber Thiago de Oliveira
• Grantee: Kleber Thiago de Oliveira
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

Studies on the photocatalyzed enantioselective synthesis of the API Brivaracetam are aimed by using enabling technologies for organic synthesis. We intend to use D-RhS photocatalysts and perform a photocatalytic screening using a high throughput reactor (12 channels) in batch and a continuous photoreactor, both developed on demand for these processes. Firstly, the synthetic approach will be tested in batch by preparing the a,b insaturated acyl-imidazole (ii) and the dihydropyridine (v) (Scheme 1). Compounds ii and v will be tested in the presence of rhodium photocatalysts by using visible light to yield the aminoketone vi. Subsequently, deprotection and cyclization reactions in vi followed by condensation with xi probably will yield the Brivaracetam. The sequence of the aimed steps will be also evaluated in order to give the best results. Scheme 1After finishing the synthesis of Brivaracetam by using both batch and continuous flow conditions, we will invest efforts to telescope the full synthetic approach in flow, aiming at an end-to-end machine assisted process. (AU)

Scientific publications

(23)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

GARBUIO, MATHEUS; DIAS, LUCAS D.; DE SOUZA, LARISSA M.; CORREA, THAILA Q.; MEZZACAPPO, NATASHA F.; BLANCO, KATE C.; DE OLIVEIRA, KLEBER T.; INADA, NATALIA M.; BAGNATO, VANDERLEI S.. ormulations of curcumin and d-mannitol as a photolarvicide against Aedes aegypti larvae: Sublethal photolarvicidal action, toxicity, residual evaluation, and small-scale field trial{*. Photodiagnosis and Photodynamic Therapy, v. 38, JUN 2022. (19/27176-8, 14/50857-8, 20/06874-6, 19/13569-8, 13/07276-1)

PEREIRA, VINICIUS R. D.; BEZERRA, MARCO A. M.; GOMEZ, MAURO R. B. P.; MARTINS, GUILHERME M.; DA SILVA, ADILSON D.; DE OLIVEIRA, KLEBER T.; DE SOUZA, RODRIGO O. M. A.; AMARANTE, GIOVANNI W.. Concise two-step chemical synthesis of molnupiravir. RSC ADVANCES, v. 12, n. 46, p. 5-pg., 2022-10-17. (22/00074-3, 19/27176-8, 20/06874-6)

MEZZACAPPO, NATASHA; DE SOUZA, LARISSA; INADA, NATALIA; DIAS, LUCAS; GARBUIO, MATHEUS; VENTURINI, FRANCINE; CORREA, THAILA; MOURA, LIDIA; BLANCO, KATE; DE OLIVEIRA, KLEBER; et al. Curcumin/d-mannitol as photolarvicide: induced delay in larval development time, changes in sex ratio and reduced longevity of Aedes aegypti. Pest Management Science, v. 77, n. 5, FEB 2021. (19/27176-8, 13/07276-1, 14/50857-8, 19/13569-8)

MARTINS, GUILHERME M.; MAGALHAES, MARIA F. A.; BROCKSOM, TIMOTHY J.; BAGNATO, VANDERLEI S.; DE OLIVEIRA, KLEBER T.. Scaled up and telescoped synthesis of propofol under continuous-flow conditions. JOURNAL OF FLOW CHEMISTRY, v. 12, n. 3, p. 9-pg., 2022-07-19. (13/07276-1, 15/11801-0, 19/27176-8, 20/06874-6, 21/01259-4)

ECHEMENDIA, RADELL; DE OLIVEIRA, KLEBER T.; BURTOLOSO, ANTONIO C. B.. Visible-Light-Promoted Synthesis of 1,3-Dicarbonyl Sulfoxonium Ylides. ORGANIC LETTERS, v. 24, n. 35, p. 5-pg., 2022-08-26. (19/27176-8, 17/23329-9, 20/06874-6, 19/12300-5, 13/07276-1, 20/07147-0)

LIMA, ALESSANDRA R.; SILVA, CICERA M.; DA SILVA, LUCAS M.; MACHULEK, AMILCAR; DE SOUZA, ANTONIO P.; DE OLIVEIRA, KLEBER T.; SOUZA, LARISSA M.; INADA, NATALIA M.; BAGNATO, VANDERLEI S.; OLIVEIRA, SAMUEL L.; et al. Environmentally Safe Photodynamic Control of Aedes aegypti Using Sunlight-Activated Synthetic Curcumin: Photodegradation, Aquatic Ecotoxicity, and Field Trial. Molecules, v. 27, n. 17, p. 13-pg., 2022-09-01. (19/27176-8, 13/07276-1)

BREDA, GABRIELA C.; FRANCA, ALEXANDRE S.; DE OLIVEIRA, KLEBER T.; ALMEIDA, RODRIGO V.; DE SOUZA, RODRIGO O. M. A.. Exploring Strategic Approaches for Cv FAP Photodecarboxylation through Violet Light Irradiation. Journal of the Brazilian Chemical Society, v. 35, n. 8, p. 5-pg., 2024-08-01. (13/07276-1, 20/06874-6, 19/27176-8)

SILVA, LUDIMILA THAYANE PAES; PEREIRA, GEORGE BUENO SANTANA; DE OLIVEIRA, GABRIELA PORTO; LIMA, MAURO ALMEIDA; DE ARAUJO NETO, JOAO HONORATO; AKINYEMI, AMOS OLALEKAN; VIEIRA, MARCELLE ALCANTARA; NASCIMENTO-JUNIOR, NAILTON MONTEIRO; DE FARIAS, RENAN LIRA; ELLENA, JAVIER ALCIDES; et al. Synthesis, characterization, cytotoxicity study, interaction with DNA and topoisomerase IIα of square-planar complexes with thiosemicarbazones. Polyhedron, v. 257, p. 9-pg., 2024-05-07. (17/15850-0, 20/06874-6, 19/11242-1, 21/04876-4, 19/27176-8, 22/02876-0)

SILVA, RODRIGO C.; BATISTA, GABRIEL M. F.; BROCKSOM, TIMOTHY J.; DE OLIVEIRA, KLEBER T.. Discovery of EDA-Complex Photochemical Reactions Using Computational Vision. ADVANCED SYNTHESIS & CATALYSIS, v. N/A, p. 10-pg., 2024-11-20. (18/00879-6, 23/04020-8, 19/27176-8, 13/07276-1, 20/06874-6)

BRAGA, FELIPE C.; MARTINS, GUILHERME M.; FRANCO, MARCELO S.; BELLI, LUIZ P. A.; DE OLIVEIRA, KLEBER T.; DE ASSIS, FRANCISCO F.. Catalyst-free photoarylation reactions promoted by visible light. ORGANIC CHEMISTRY FRONTIERS, v. 11, n. 4, p. 25-pg., 2023-12-28. (21/06110-9, 13/07276-1, 20/06874-6, 22/00074-3, 23/04020-8, 19/27176-8)

GABRIELA C. BRÊDA; ALEXANDRE S. FRANÇA; KLEBER T. DE OLIVEIRA; RODRIGO V. ALMEIDA; RODRIGO O. M. A. DE SOUZA. Exploring Strategic Approaches for CvFAP Photodecarboxylation through Violet Light Irradiation. Journal of the Brazilian Chemical Society, v. 35, n. 8, 2024-03-22. (13/07276-1, 20/06874-6, 19/27176-8)

TISOCO, ISADORA; DONATONI, MARIA CAROLINA; VIEIRA VICTORIA, HENRIQUE FERNANDES; DE TOLEDO, JOSE ROBERTO; KRAMBROCK, KLAUS; CHAVES, OTAVIO AUGUSTO; DE OLIVEIRA, KLEBER THIAGO; IGLESIAS, BERNARDO ALMEIDA. Photophysical, photooxidation, and biomolecule-interaction of meso-tetra(thienyl)porphyrins containing peripheral Pt(ii) and Pd(ii) complexes. Insights for photodynamic therapy applications. DALTON TRANSACTIONS, v. 51, n. 4, JAN 2022. (19/27176-8, 20/06874-6, 13/07276-1)

LINARES, IRWIN A. P.; MARTINELLI, LETICIA P.; MORITZ, MILENE N. O.; SELISTRE-DE-ARAUJO, HELOISA S.; DE OLIVEIRA, KLEBER T.; PERUSSI, JANICE RODRIGUES. Cytotoxicity of structurally-modified chlorins aimed for photodynamic therapy applications. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY, v. 425, MAR 1 2022. (20/06874-6, 13/07276-1, 19/27176-8)

ROSA, GABRIEL H. S.; SANTOS, THIAGO I. S.; BROCKSOM, TIMOTHY J.; DE OLIVEIRA, KLEBER T.. Diverse continuous photooxygenation reactions of (+) and (-)-alpha-pinenes to the corresponding pinocarvones or trans-pinocarveols. REACTION CHEMISTRY & ENGINEERING, v. N/A, p. 8-pg., 2022-12-05. (20/06874-6, 19/27176-8, 13/07276-1, 20/04114-4)

PEREIRA, FELIPE; DE ANNUNZIO, SARAH RAQUEL; LOPES, THAIS DE ASSIS; DE OLIVEIRA, KLEBER THIAGO; CILLI, EDUARDO MAFFUD; BARBUGLI, PAULA ABOUD; FONTANA, CARLA RAQUEL. Efficacy of the combination of P5 peptide and photodynamic therapy mediated by bixin and chlorin-e6 against Cutibacterium acnes biofilm. Photodiagnosis and Photodynamic Therapy, v. 40, p. 13-pg., 2022-12-01. (19/27176-8, 18/09088-1, 19/08668-7, 20/06874-6, 13/07276-1)

DE SOUZA, ALINE A. N.; BARTOLOMEU, ALOISIO DE A.; BROCKSOM, TIMOTHY J.; NOEL, TIMOTHY; DE OLIVEIRA, KLEBER T.. Direct Synthesis of ?-Sulfenylated Ketones under Electrochemical Conditions br. Journal of Organic Chemistry, v. 87, n. 9, p. 10-pg., 2022-05-06. (15/11801-0, 19/27176-8, 13/07276-1, 20/06874-6)

GRUNDKE, CAROLINE; SILVA, RODRIGO C.; KITZMANN, WINALD R.; HEINZE, KATJA; DE OLIVEIRA, KLEBER T.; OPATZ, TILL. Photochemical ?-Aminonitrile Synthesis Using Zn-Phthalocyaninesas Near-Infrared Photocatalysts. Journal of Organic Chemistry, v. 87, n. 9, p. 13-pg., 2022-05-06. (18/00879-6, 20/06874-6, 19/27176-8)

FRANCO, MARCELO S.; SILVA, RODRIGO C.; ROSA, GABRIEL H. S.; FLORES, LARA M.; DE OLIVEIRA, KLEBER T.; DE ASSIS, FRANCISCO F.. Synthesis of the Brivaracetam Employing Asymmetric Photocatalysis and Continuous Flow Conditions. ACS OMEGA, v. 8, n. 25, p. 9-pg., 2023-06-14. (20/06874-6, 19/27176-8, 20/04114-4, 18/00879-6)

ULIANA, MARCIANA PIERINA; RODRIGUES, ANDREIA DA CRUZ; ONO, BRUNO ANDRADE; PRATAVIEIRA, SEBASTIAO; DE OLIVEIRA, KLEBER THIAGO; KURACHI, CRISTINA. Photodynamic Inactivation of Microorganisms Using Semisynthetic Chlorophyll a Derivatives as Photosensitizers. Molecules, v. 27, n. 18, p. 14-pg., 2022-09-01. (11/19720-8, 20/06874-6, 19/27176-8, 11/13993-2, 08/57858-9, 09/54035-4, 13/07276-1)

SILVA, KAMILA JESSIE SAMMARRO; LIMA, ALESSANDRA RAMOS; DIAS, LUCAS DANILO; GARBUIO, MATHEUS; DE SOUZA, MARIANA; CORREA, THAILA QUATRINI; BLANCO, KATE CRISTINA; SANCHES, EDGAR APARECIDO; BAGNATO, VANDERLEI SALVADOR; INADA, NATALIA MAYUMI. Photodynamic processes for water and wastewater treatment: a review. LASER PHYSICS LETTERS, v. 21, n. 5, p. 18-pg., 2024-05-01. (13/07276-1, 20/06874-6, 14/50857-8, 23/11853-6, 19/27176-8)

GARBUIO, MATHEUS; LIMA, ALESSANDRA RAMOS; SILVA, KAMILA JESSIE SAMMARRO; DE SOUZA, MARIANA; INADA, NATALIA MAYUMI; DIAS, LUCAS DANILO; BAGNATO, VANDERLEI SALVADOR. Influence of temperature combined with photodynamic inactivation on the development of Aedes aegypti. Photodiagnosis and Photodynamic Therapy, v. 45, p. 8-pg., 2024-01-23. (13/07276-1, 20/06874-6, 14/50857-8, 23/11853-6, 19/27176-8)

BRAGA, FELIPE C.; RAMOS, TIAGO O.; BROCKSOM, TIMOTHY J.; DE OLIVEIRA, KLEBER T.. Synthesis of Fentanyl under Continuous Photoflow Conditions. ORGANIC LETTERS, v. 24, n. 45, p. 6-pg., 2022-11-08. (13/07276-1, 19/27176-8, 21/06110-9)

MULLER, ANDRESSA, V; FAUSTINO, LEANDRO A.; DE OLIVEIRA, KLEBER T.; PATROCINIO, ANTONIO O. T.; POLO, ANDRE S.. Visible-Light-Driven Photocatalytic CO2 Reduction by Re(I) Photocatalysts with N-Heterocyclic Substituents. ACS CATALYSIS, v. 13, n. 1, p. 14-pg., 2022-01-06. (16/24020-9, 18/08038-0, 19/27176-8, 20/06874-6)