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Applicantion of organometallic reagents in the directed functionalization of quinolines aimming the synthesis of medicinal interest compounds

Grant number: 15/21364-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2016
Effective date (End): February 29, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Giuliano Cesar Clososki
Grantee:Valter Eduardo Murie
Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):19/05838-9 - Flow modified Lehmstedt-Tanasescu reactions for the scaled production of medicinally important heterocyclic building blocks, BE.EP.DR

Abstract

In the last few years, mixed lithium-magnesium and lithium-zinc amides have been used to prepare several functionalized heterocycles and aromatic heterocycles. Quinolines have a highlighted position among heterocycles of fused rings. The quinoline scaffold can be found out in different compounds with biologic activities such as antimalarial, anticancer and others. Thus, this project aims to investigate the use of mixed lithium-magnesium amides (such as TMPMgCl*LiCl and TMP2Mg*2LiCl) and lithium-zinc amides (TMPZnCl*LiCl) in order to generate functionalized quinoline derivatives envisaging to obtain bioactive molecules. In addition to directed metalation reaction, we intend to study the synthesis of some quinoline derivatives by means of halogen-metal exchange reaction using i-PrMgCl*LiCl (turb-Grignard) in order to prepare chiral derivatives.Moreover, we intend to study directed remote metalation reaction as an interesting application to obtain complex quinoline derivatives. This methodology envisages to obtain polycyclic quinolines. All quinoline derivatives will be sent to biologic ativity evaluation in order to identify molecules as future drug candidates. Finally, reactions that present promising results will be investigated in microreactors of flow chemistry as a way to evaluate the potential of this technique to scale-up the developed methodologies as well as optimization of reaction parameters such as time, temperature and yield.

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. Web of Science Citations: 1.
MURIE, VALTER E.; NISHIMURA, RODOLFO H. V.; ROLIM, LARISSA A.; VESSECCHI, RICARDO; LOPES, NORBERTO P.; CLOSOSKI, GIULIANO C. Base-Controlled Regioselective Functionalization of Chloro-Substituted Quinolines. Journal of Organic Chemistry, v. 83, n. 2, p. 871-880, JAN 19 2018. Web of Science Citations: 6.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.