Application of continuous flow chemistry in the synthesis of Active Pharmaceutical Ingredients (APIs): cannabidiol, fentanyl, and ibuprofen

• Grant number: 21/06110-9
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: December 01, 2021
• End date: November 30, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Kleber Thiago de Oliveira
• Grantee: Felipe Camargo Braga
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil

Abstract

In this research project, we propose the development of an innovative synthesis of 3 important Active Pharmaceutical Ingredients (APIs) with high and imminent demand on the pharmaceutical market. Our proposal encompasses the development of batch process and continuous flow, using some photocatalytic methods recently developed in LQBO-UFSCar. In the first subproject, it is proposed the synthesis of cannabidiol by initial preparation of olivetolic acid and the fragment p-mentadienol (recently prepared in LQBO), with sequential C-C bond to connect both moieties. In the subproject 2 we propose the use of a photocatalytic step, essential for the synthesis of fentanyl in batch regime or continuous flow. In an analogous way, recent methodologies and photocatalytic reactors (batch and flow) developed in LQBO will be applied in this study. In subproject 3 we intend to develop the synthesis of ibuprofen, that despite being a low-cost and well-known API, still displays some problems in its commercial synthesis, deserving further expedient synthetical investigations. In this case, we will apply a photocatalytic step developed in LQBO that requires diazonium salts and porphyrin derivatives (0.5 mol) that act as Single Electron Transfer (SET) photocatalysts. In brief, we aim to apply the knowledge and continuous flow solutions to synthesize relevant molecules. It is worth to point out that this project is aligned with high technologies and current demands in society, offering this candidate essential training in state-of-the-art synthetic chemistry for the pharmaceutical market - knowledge and practice in Flow Chemistry. (AU)

Scientific publications

(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)

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)