Applications of technologies and synthetic methodologies developed under continuous flow conditions at LQBO-UFSCar for the preparation of molecules with biological activities and APIs

• Grant number: 20/06874-6
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2021
• End date: March 31, 2023
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• 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
• Associated researchers: Timothy John Brocksom
• Associated scholarship(s): 21/13184-9 - Technical Training in the Bioorganic Chemistry Laboratory at UFSCar - LQBO, BP.TT

Abstract

In this research project we propose the application of the methodologies recently developed in our research laboratory (LQBO-UFSCar) for the synthesis of bioactive molecules and active pharmaceutical ingredients (APIs) such as (-) - aritasone, favipiravir, and ibuprofen. For these syntheses, we will use continuous flow reaction systems, and simple solutions also developed in our laboratory. This project is divided into 3 subprojects (Figure i). In the first (Project 1) we will apply the photooxygenation system working under continuous flow regime for the synthesis and scale-up of (-) - pinocarvone. Then, we will study the synthesis of (-) - aritasone through the hetero-Diels-Alder reaction under extreme conditions (high temperature and pressure). In the second (Project 2) we will invest efforts for the synthesis of favipiravir using continuous photocatalyzed reaction conditions and thermal protocols to obtain this API in a few steps and low cost. We emphasize that this proposed synthesis has unprecedented steps concerning the syntheses described in the literature, namely a photocatalytic fluorination step which we intend to develop. Similarly, in the last subproject (Project 3), we intend to develop a synthesis of ibuprofen, which is a well-known and relatively low-cost API, but still deserves more advantageous synthetic investigations. In this case, we will apply a photocatalytic step developed in our group that uses diazonium salts and porphyrin derivatives (0.5mol%) as photocatalysts (single electron transfer). In general, we envisioning the appreciation of many results from our team applying the developed solutions in the synthesis of relevant molecules. It is worth mentioning that this project is aligned with the top 10 technologies and current demands of our society, giving a relevant opportunity to students as well as valuable training in flow chemistry, which is a well-required skill by the current job market. (AU)

Scientific publications

(17)

(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)

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)

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)

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)

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)

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)

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)

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)

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)

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)

IGLESIAS, BERNARDO ALMEIDA; PERANZONI, NICKOLAS PIPPI; FARIA, SOPHIA IWERSEN; TRENTIN, LUANA BELO; SCHUCH, ANDRE PASSAGLIA; CHAVES, OTAVIO AUGUSTO; BERTOLONI, RENAN RIBEIRO; NIKOLAOU, SOFIA; DE OLIVEIRA, KLEBER THIAGO. DNA-Interactive and Damage Study with meso-Tetra(2-thienyl)porphyrins Coordinated with Polypyridyl Pd(II) and Pt(II) Complexes. Molecules, v. 28, n. 13, p. 16-pg., 2023-07-01. (22/03478-8, 20/06874-6, 13/07276-1)

COSTA E SILVA, RODRIGO; VEGA, CLARA; REGNIER, MORGAN; CAPALDO, LUCA; WESENBERG, LARS; LOWE, GRACE; DE OLIVEIRA, KLEBER THIAGO; NOEL, TIMOTHY. Electrosynthesis of Aryliminophosphoranes in Continuous Flow. ADVANCED SYNTHESIS & CATALYSIS, v. N/A, p. 7-pg., 2023-08-09. (18/00879-6, 20/06874-6, 21/09145-8)

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)

DE CASTRO, PEDRO P.; MARTINS, GUILHERME M.; GOMES, RONEWALBER B.; SIMOSO, GUILHERME B.; AMARANTE, GIOVANNI W.; BROCKSOM, TIMOTHY J.; DE OLIVEIRA, KLEBER T.. Electrochemical reduction of 5-benzylidene thiazolidine-2,4-diones: a greener approach to the preparation of glitazone APIs. CHEMICAL COMMUNICATIONS, v. 59, n. 61, p. 4-pg., 2023-07-05. (20/06874-6, 21/13924-2, 21/14446-7, 22/00074-3)