Development of novel continuous flow approaches towards the preparation of pharmaceuticals: Axitinib, Lacosamide, Pioglitazone and Rosiglitazone

• Grant number: 21/13924-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2022
• End date: March 03, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Kleber Thiago de Oliveira
• Grantee: Pedro Pôssa de Castro
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

This project aims the development of novel synthetic approaches concerning the preparation of four important pharmaceuticals, employed in the treatment of different diseases, under batch and continuous flow conditions. In addition to classic synthetic strategies, the use of modern approaches, such as photochemical steps, would also be employed aiming to allow the preparation of the desired pharmaceuticals through simple and readily available starting materials. To this purpose, the first subproject (subproject 1 - figure 1) consists of Axitinib synthesis through a series of photochemical steps, including the formation of two key chemical bonds through the visible light irradiation of Electron-Donor Acceptor complexes (EDA complexes). The second subproject (subproject 2 - figure 1) involves the asymmetric preparation of Lacosamide through two different approaches: the first involving the formation of an azlactone as key intermediate, which after a dynamic kinetic resolution ring opening step would afford the desired pharmaceutical, and the second proposal involving an asymmetric four-component Ugi reaction followed by amine deprotection. Finally, the third subproject (subproject 3 - figure 1) involves the development of alternative routes for the preparation of Pioglitazone and Rosiglitazone, which still present problems in their synthesis and lack simpler approaches towards their preparation. (AU)

Scientific publications

(5)

(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)

CARVALHO, MARCELO H. R.; AMARANTE, GIOVANNI W.; DE CASTRO, PEDRO P.. Recent Synthetic Developments of Asymmetric Multicomponent Transformations: Strecker, Mannich, Passerini and Ugi Reactions. Journal of the Brazilian Chemical Society, v. 34, n. 8, p. 30-pg., 2023-05-25. (21/13924-2)

BATISTA, GABRIEL M. F.; DE CASTRO, PEDRO P.. Advances in the Transition Metal Catalyzed Carboxylation of Aryl Electrophiles: a Field Full of Opportunities for the Brazilian Chemical Society. REVISTA VIRTUAL DE QUIMICA, v. N/A, p. 18-pg., 2023-02-08. (21/13924-2)

DE SIQUEIRA, MARCELO M.; DE CASTRO, PEDRO P.; DOS SANTOS, JULIANA A.; FLORES, LEONA S.; DE PAIVA, WALYSSON F.; FERNANDES, SERGIO A.; AMARANTE, GIOVANNI W.. On the Bronsted acid-catalyzed aza-Michael reaction of isoxazol-5-ones to enones: reaction optimization, scope, mechanistic investigations and scale-up. REACTION CHEMISTRY & ENGINEERING, v. 8, n. 5, p. 12-pg., 2023-02-20. (21/13924-2)

SANTOS, WILLIAM A. B.; DE CASTRO, PEDRO P.; XAVIER, FERNANDO R.; BRAGA, ANTONIO L.; MARTINS, GUILHERME M.; MENDES, SAMUEL R.. Electrosynthesis of Flavanones via oxa-Michael Addition Using Sacrificial Electrodes. SYNTHESIS-STUTTGART, v. N/A, p. 8-pg., 2023-03-22. (22/00074-3, 21/13924-2)

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)