APIs synthesis using enabling technologies: approaches involving electrosynthesis and photocatalysis under continuous flow conditions

• Grant number: 23/04020-8
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2025
• 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

Abstract

In this project we propose the continuous flow syntheses of 3 active pharmaceutical ingredients (APIs): i) ibuprofen; ii) cannabidiol; iii) axitinib (Figure i). In subproject (i) - ibuprofen synthesis - we intend to study the iodination of isobutylbenzene via electrosynthesis to then convert the iodinated intermediate into ibuprofen after two photocatalytic steps, similar to a methodology that was recently developed in our laboratory. In subproject (ii) - synthesis of cannabidiol - we intend to study the scale-up of the recently published protocol (a partnership with our team) which involves the production of p-menta-2,8-dien-1-ol from limonene using oxygen singlet. The continuous synthesis of olivetol and its derivatives will also be studied to later prepare cannabidiol. In subproject (iii) we intend to invest efforts in the synthesis of axitinib through an unprecedented and challenging multi-step route, involving two photocatalyzed steps. In general, with this project, we seek to value the efforts and results of our team obtained in recent years, applying knowledge and solutions in the synthesis of relevant molecules. It is worth mentioning that this project is fully connected with the high technologies and current demands of society, providing high-level training to students in a very required field (Flow Chemistry). (AU)

Scientific publications

(10)

(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)

MARTINS, GUILHERME M.; BRAGA, FELIPE C.; DE CASTRO, PEDRO P.; BROCKSOM, TIMOTHY J.; DE OLIVEIRA, KLEBER T.. Continuous flow reactions in the preparation of active pharmaceutical ingredients and fine chemicals. CHEMICAL COMMUNICATIONS, v. 60, n. 24, p. 14-pg., 2024-02-29. (23/04020-8, 22/00074-3, 21/06110-9, 21/13924-2)

BRAGA, FELIPE C.; DA SILVA, FELIPE L. N.; RAMOS, TIAGO DE O.; ROSA, JOAO G. H.; ARAUJO, ERICA DE A.; JUNIOR, NELSON F. C.; WENDLER, EDISON P.; BEATRIZ, ADILSON; DE SOUZA, RODRIGO O. M. A.; BROCKSOM, TIMOTHY J.; et al. Batch and Continuous Flow Total Synthesis of Cannabidiol. CHEMISTRY-AN ASIAN JOURNAL, v. 19, n. 20, p. 7-pg., 2024-10-16. (13/07276-1, 20/06874-6, 23/04020-8, 21/06110-9)

DO PRADO-SILVA, LEONARDO; BRANCINI, GUILHERME THOMAZ PEREIRA; BACHMANN, LUCIANO; DE OLIVEIRA, KLEBER THIAGO; BRAGA, GILBERTO UBIDA LEITE; SANT'ANA, ANDERSON S.. Controlling Alicyclobacillus acidoterrestris spores contamination on orange surfaces using different photosensitizers and light sources. FOOD CONTROL, v. 167, p. 8-pg., 2024-08-10. (13/07276-1, 23/04020-8, 16/11386-5, 23/18197-7)

CARVALHO, MARCELO H. R.; DE CASTRO, PEDRO P.; DE OLIVEIRA, KLEBER T.; AMARANTE, GIOVANNI W.. Enhancing Efficiency and Sustainability: Unleashing the Potential of Continuous Flow in Multicomponent Reactions. CHEMSUSCHEM, v. N/A, p. 16-pg., 2024-11-11. (23/04020-8)

MARRA, ISABELLA F. S.; SILVA, LARISSA P.; DE CASTRO, PEDRO P.; FLORES, LEONA S.; DE OLIVEIRA, KLEBER T.; DE SOUZA, PAULO E. N.; NETO, BRENNO A. D.; DOS SANTOS, HELIO F.; AMARANTE, GIOVANNI W.. Visible-Light-Enabled Dual-Catalysis Approach to Stereoselective [2+2] Cycloaddition of Erlenmeyer-Plöchl Azlactones. ASIAN JOURNAL OF ORGANIC CHEMISTRY, v. 13, n. 11, p. 9-pg., 2024-10-18. (23/04020-8, 21/13924-2)

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)

DE CARVALHO, GABRIEL GARCIA; VIEIRA, BASILIO RODRIGUES; CARVALHO, JHONATAN DE SOUZA; DE SOUSA, FREDERICO BARBOSA; CERRI, PAULO SERGIO; DE OLIVEIRA, KLEBER THIAGO; CHORILLI, MARLUS; ZANDIM-BARCELOS, DANIELA LEAL; SPOLIDORIO, LUIS CARLOS; SPOLIDORIO, DENISE MADALENA PALOMARI. Multiple PDT sessions with chlorin-e6 and LL-37 loaded-nanoemulsion provide limited benefits to periodontitis in rats. Photodiagnosis and Photodynamic Therapy, v. 49, p. 9-pg., 2024-09-23. (13/07276-1, 20/04499-3, 23/04020-8, 18/09088-1, 21/05881-1)

SANTUCCI, PEDRO M.; DE OLIVEIRA, CAROLINE R.; MONTEIRO, AFIF F.; MENDES, GIOVANA R.; DE AMORIM, MARCELO R.; ROSA, GABRIEL H. S.; SETTE, LARA D.; MARCHI, RAFAEL C.; DEFLON, VICTOR M.; DOS SANTOS, PEDRO H. T.; et al. Improved production of palitantin by design of experiments and semi-synthesis of palitantin derivatives for bioactivity assessment. Fitoterapia, v. 180, p. 10-pg., 2024-12-05. (20/01229-5, 23/04020-8, 22/01063-5, 19/17721-9, 23/07721-7, 15/01017-0)

GUILHERME M. MARTINS; KLEBER T. DE OLIVEIRA. EMERGING TRENDS OF ORGANIC ELECTROSYNTHESIS IN BRAZIL. Química Nova, v. 48, n. 1, 2024-06-07. (23/04020-8, 22/00074-3)