Applicantion of Organometallic Reagents in the Directed Functionalization of Quinolines Aimming the Synthesis of Medicinal Interest Compounds

• Grant number: 15/21364-6
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: January 01, 2016
• End date: February 29, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Valter Eduardo Murie
• Host 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

(8)

(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, V, RODOLFO H.; DOS SANTOS, THIAGO; MURIE, VALTER E.; FURTADO, LUCIANA C.; COSTA-LOTUFO, V, LETICIA; CLOSOSKI, GIULIANO C.. Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents. Beilstein Journal of Organic Chemistry, v. 17, p. 2968-2975, DEC 22 2021. (15/17177-6, 17/18235-5, 15/21364-6, 18/14150-8, 20/08987-2, 15/01466-9)

DOS SANTOS, THIAGO; ORENHA, HENRIQUE P.; MURIE, VALTER E.; VESSECCHI, RICARDO; CLOSOSKI, GIULIANO C.. Selective Metalation and Functionalization of Fluorinated Nitriles Using 2,2,6,6-Tetramethylpiperidyl Bases. ORGANIC LETTERS, v. 23, n. 19, p. 7396-7400, OCT 1 2021. (15/21364-6, 18/14150-8, 15/01017-0)

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)

NISHIMURA, RODOLFO H. V.; MURIE, VALTER E.; VESSECCHI, RICARDO; CLOSOSKI, GIULIANO C.. Selective Functionalization of Benzo-FusedN-Heterocycles by Using In Situ Trapping Metalations. CHEMISTRYSELECT, v. 5, n. 36, p. 6-pg., 2020-09-30. (18/14150-8, 14/23604-1, 15/01466-9, 15/21364-6)

DARTAGNAN S. P. FERREIRA; VALTER E. MURIE; THIAGO DOS SANTOS; PAULO C. VIEIRA; GIULIANO C. CLOSOSKI. Recentes avanços na funcionalização seletiva de quinolinas. Química Nova, v. 44, n. 5, p. 599-615, 2021-07-26. (15/21364-6, 18/14150-8, 19/05838-9)

MURIE, VALTER E.; NICOLINO, V, PAULA; DOS SANTOS, THIAGO; GAMBACORTA, GUIDO; NISHIMURA, V, RODOLFO H.; PEROVANI, ICARO S.; FURTADO, LUCIANA C.; COSTA-LOTUFO, V, LETICIA; DE OLIVEIRA, ANDERSON MORAES; VESSECCHI, RICARDO; et al. Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents. Journal of Organic Chemistry, v. 86, n. 19, p. 13402-13419, OCT 1 2021. (13/00758-0, 15/21364-6, 19/05838-9, 18/14150-8, 15/17177-6)

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. (15/01466-9, 15/21364-6, 15/12811-9, 14/23604-1)

BOZZINI, LEANDRO A.; DOS SANTOS, THIAGO; MURIE, VALTER E.; DE MELLO, MURILO B. M.; VESSECCHI, RICARDO; CLOSOSKI, GIULIANO C.. Regioselective Functionalization of Ester-, Amide-, Carbonate-, and Carbamate-Substituted 2-Phenyl-2-oxazolines with Mixed Lithium-Magnesium Amides. Journal of Organic Chemistry, v. 86, n. 1, p. 1204-1215, JAN 1 2021. (18/14150-8, 15/21364-6, 14/23604-1)

Academic Publications

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

MURIE, Valter Eduardo. Regioselective functionalization of chloroquinolines to synthesize compounds of medicinal interest. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.