Application and development of continuous flow processes in the synthesis of fentanylic opioids

• Grant number: 16/12718-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: August 01, 2016
• End date: January 31, 2021
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Artur de Lara Lima Vaz
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In the past few years, organic synthesis in continuous flow has become a powerful tool in mid and large-scale production of Active Pharmaceutical Ingredients (APIs) in reduced spaces. In this context, the following project focus in the search for solutions in the synthesis of API precursors scaffolds by developing continuous flow protocols compatible with classic organic synthesis strategies, such as multicomponent reactions and use of organometallic intermediates. Specifically, the scientific activities will be directed on obtaining analgesic opioids analogue to Fentanyl, including 4-anilidopiperidines, 4-acyl-4-anilidopiperidines and 4-aryl-4-anilidopiperidines, which are of great importance in the therapy of pain related to many conditions, including cancer. While developing continuous flow methodologies, we expect to be able to provide fentanyl analogues in preparative scale, as this is a crucial step in establishing innovative processes in the pharmaceutical industry. Finally, in addition to furnishing compounds of known therapeutic importance, the project will allow for the preparation of novel fentanyl analogues with structural diversity that, after biological evaluation, could expand the current knowledge involving structure-activity relationships of this important class of compounds. (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)

NISHIMURA, RODOLFO H. V.; VAZ, ARTUR DE L. L.; BOZZINI, LEANDRO A.; MURIE, VALTER E.; CLOSOSKI, GIULIANO C.. Recent applications of magnesium- and Zinc-TMP amides in the synthesis of bioactive targets. Tetrahedron, v. 75, n. 4, p. 464-474, JAN 25 2019. (16/12718-1, 15/21364-6, 15/01466-9, 18/14150-8)

LIMA, RAFAELY N.; DE L. L. VAZ, ARTUR; CLOSOSKI, GIULIANO C.; PORTO, ANDRE L. M.. Sustainable Synthesis of Amides from Ethyl 3-(4-Hydroxyphenyl) Propionate. CHEMISTRYSELECT, v. 6, n. 13, p. 3271-3276, APR 8 2021. (14/18257-0, 18/14150-8, 16/12718-1)

ARTUR DE LARA LIMA VAZ; JOÃO LUIS CALLEGARI LOPES; GIULIANO CESAR CLOSOSKI. Continuous flow Aza-Michael reaction for preparing the fast-acting synthetic opioid drug Remifentanil. Brazilian Journal of Pharmaceutical Sciences, v. 59, 2023-06-16. (22/05327-7, 16/12718-1)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

VAZ, Artur de Lara Lima. Application of continuous flow processes in the synthesis of fentanyl opioids. 2022. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.