DIRECTED FUNCTIONALIZATION OF ARENES AND HETEROARENES AIMIMNG THE SYNTHESIS OF SUBSTANCES OF MEDICINAL INTEREST

• Grant number: 15/12811-9
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2015
• End date: January 31, 2018
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Giuliano Cesar Clososki
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

In this project we intend to study the application of mixed lithium, magnesium and zinc organometallic reagents in the directed functionalization of aromatic and heterocyclic substrates of great scientific and technological interest, mainly for Medicinal Chemistry. In this sense, directed metalation or halogen/metal exchange reactions in a series of indolizines, imidazo-pyridines, quinazolines, quinazolinones and oxazolines, among other targets that present interest in the course of the project, should allow isolation of highly functionalized aromatic and heterocyclic derivatives, many of which with new compounds in the literature. In order to better understand, rationalize and plan regioselective metallation reactions, computational chemistry tools will be used in the structural evaluation of all synthetic targets. In addition, to demonstrate the importance of the developed synthetic methodologies, we plan to apply them in the synthesis or structural modification of molecules of medicinal interest, such as the anxiolytic alpidem and the anti-tumor verubulin. (AU)

Scientific publications

(7)

(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)

SILVA, RAFAELA M.; OKANO, LAURA T.; RODRIGUES, J. AUGUSTO R.; CLOSOSKI, GIULIANO C.. Extractive biocatalysis in the asymmetric reduction of alpha-alkyl, beta-aryl enones by Baker's yeast. TETRAHEDRON-ASYMMETRY, v. 28, n. 7, p. 939-944, JUL 15 2017. (15/12811-9)

BOZZINI, LEANDRO A.; BATISTA, JOAO H. C.; DE MELLO, MURILO B. M.; VESSECCHI, RICARDO; CLOSOSKI, GIULIANO C.. Selective functionalization of cyano-phenyl-2-oxazolines using TMPMgCl center dot LiCl. Tetrahedron Letters, v. 58, n. 44, p. 4186-4190, NOV 1 2017. (15/12811-9, 11/12589-3, 14/23604-1)

MURIE, VALTER E.; MARQUES, LUCAS M. M.; SOUZA, GLORIA E. P.; OLIVEIRA, ANDERSON R. M.; LOPES, NORBERTO P.; CLOSOSKI, GIULIANO C.. Acetaminophen Prodrug: Microwave-Assisted Synthesis and in vitro Metabolism Evaluation by Mass Spectrometry. Journal of the Brazilian Chemical Society, v. 27, n. 6, p. 1121-1128, JUN 2016. (13/17658-9, 15/12811-9, 14/50265-3)

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)

SILVA, SIMONE CAVALCANTE; RODRIGUES, SHIRLEY M. M.; NARDINI, VIVIANI; VAZ, ARTUR DE L. L.; PALARETTI, VINICIUS; JOSE DA SILVA, GIL VALDO; VESSECCHI, RICARDO; CLOSOSKI, GIULIANO C.. Conformational dynamics of 4-formylaminoantipyrine based on NMR and theoretical calculations. Journal of Molecular Structure, v. 1163, p. 280-286, JUL 5 2018. (15/12811-9, 14/23604-1)

FREIRE FRANCO, MARCIA SILVANA; DE PAULA, MURILO HELDER; GLOWACKA, PAULINA CECYLIA; FUMAGALLI, FERNANDO; CLOSOSKI, GIULIANO CESAR; EMERY, FLAVIO DA SILVA. Palladium-catalyzed C-H alkenylation of quinoxaline N-oxide enabled by a mono-N-protected amino acid. Tetrahedron Letters, v. 59, n. 26, p. 2562-2566, JUN 27 2018. (12/20990-2, 14/50265-3, 17/21146-4, 15/12811-9)

DE MELLO, MURILO B. M.; DE OLIVEIRA, ANTONIO A. F.; DE OLIVEIRA, CAROLINE L.; ULTRAMARI, MARIAH A.; GAETA, FERNANDO H. S.; MASCARELLO, ALESSANDRA; GUIMARAES, CRISTIANO R. W.; DE FREITAS, MILLER N.; CUNHA, CARLOS E.; LOURENCO, TIAGO C.; et al. Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity. Journal of the Brazilian Chemical Society, v. 30, n. 7, p. 1415-1424, JUL 2019. (18/14150-8, 15/12811-9, 14/50265-3)