Directed functionalization of quinazolines and quinazolinones aiming the synthesis of bioactive substances

• Grant number: 15/01466-9
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): July 01, 2015
• Effective date (End): July 31, 2019
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal researcher: Giuliano Cesar Clososki
• Grantee: Rodolfo Hideki Vicente Nishimura
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 18/08856-5 - Metalations under flow conditions., BE.EP.DR

Abstract

Due to their importance and versatility demonstrated in the recent years, organometallic bases have been widely employed in the preparation of many functionalized aromatic and heteroaromatic rings. Among of six membered heterocyclic compounds, quinazolines and quinazolinones occupy a central position and their structures are commonly found in several molecules presenting biological activities such as anti-inflammatory, antioxidant, antimicrobial, antihypertensive, anticancer, among others. Thus, in this project our main objective is to investigate the applicability of the mixed amides of magnesium-lithium (TMPMgCl*LiCl and TMP2Mg*2LiCl) and zinc-lithium (TMPZnCl*LiCl) in the fuctionalization of quinazolinic derivatives aiming the preparation of bioactive molecules. As an alternative for the metallation reactions, we also intend to study the functionalization of halogenated quinazolines by the reaction of halogen-metal exchange using i-PrMgCl*LiCl (turbo-Grignard).Moreover, aiming to demonstrate the importance of the developed synthetic methodologies, they will be applied to the synthesis of Verubulin and its analogues with basic structure of 4-aminoquinazolines, which are found in a number of drugs with anticancer activity. Finally, the reactions exhibiting the most promising results will be investigated under continuous flow conditions to evaluate the potential of this technique in scaling up processes. (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, 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. Web of Science Citations: 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. 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.

Academic Publications

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

NISHIMURA, Rodolfo Hideki Vicente. Functionalization of N-heterocyclic compounds aiming the synthesis of bioactive substances. 2019. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto (PCARP/BC) Ribeirão Preto.