Development of Self-Optimization Platforms for the Multi-Step Synthesis of APIs

• Grant number: 23/07466-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2023
• End date: July 31, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Júlio Cezar Pastre
• Grantee: Rodrigo Costa e Silva
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 21/06661-5 - Enabling technologies for the sustainable chemical synthesis of platform molecules, new chemicals and bioactive compounds, AP.BIOEN.JP2

Abstract

The multi-step synthesis in a continuous flow regime represents a challenge and the automation of these processes will allow the fast and efficient generation of data. By transferring the process to the computer, iterative experiments can be designed and performed from the data that the system acquires, culminating in a closed loop of automated optimization, commonly referred to as a self-optimizing system. In this project, we intend to implement in the group a platform for the automation of chemical syntheses and, in particular, for the multi-step synthesis of APIs such as dolutegravir. This subproject is aligned with AXIS 3 of the general proposal and, in collaboration with Dr. Richard Bourne from the University of Leeds, aims to build a modular continuous flow system for automating organic reactions. The system will incorporate devices for inline analysis and can be easily reconfigured to optimize single or multi-step processes, allowing a comprehensive understanding of the process with minimal user intervention. The platform will initially be used in the synthesis of an essential drug for the treatment of HIV, dolutegravir, which may culminate in a new patentable and potentially more efficient production route.

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)

LOPES, ERIC F.; COSTA E SILVA, RODRIGO; SOUZA, RAFAEL A. C.; FERNANDEZ, PABLO SEBASTIAN; PASTRE, JULIO CEZAR. Stereoselective Electrochemical Synthesis of E-Tetrasubstituted Haloalkenyl Chalcogenides. CHEMISTRY-AN ASIAN JOURNAL, v. N/A, p. 8-pg., 2024-10-31. (23/07466-7, 23/02929-9, 23/01930-3, 21/06661-5, 17/11986-5)

FERREIRA, LUCAS CORAL; GALAVERNA, RENAN DE SOUZA; MCBRIDE, TOM; SILVA, RODRIGO COSTA E; BROWNE, DUNCAN L.; PASTRE, JULIO CEZAR. Fast and scalable continuous flow synthesis of butenolides and coumarins. REACTION CHEMISTRY & ENGINEERING, v. N/A, p. 6-pg., 2025-02-10. (21/06661-5, 23/07466-7)