Selective aromatic functionalization: Methodological Studies and new applications in the synthesis of BIOATIVE compounds

• Grant number: 18/14150-8
• Support Opportunities: Regular Research Grants
• Duration: September 01, 2018 - February 28, 2021
• 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 the present project we intend to study the potential of organometallic reagents in the development of methodologies for selective 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 aryl nitriles, quinolines, indolizines and quinoxalines, among other targets that may be of interest in the course of the project should allow the isolation of new highly functionalized aromatic and heterocyclic compounds. With the aim to better understand, rationalize and plan regioselective metalation reactions, computational chemistry tools will be used in the structural evaluation of all synthetic targets. Finally, in order to demonstrate the synthetic importance of the developed methodologies, applications in the preparation or structural modification of substances of medicinal interest, such as quinazolines and quinolines with potential antitumor activity, will be carried out. (AU)

Scientific publications

(14)

(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)

DOS SANTOS, THIAGO; GRUNDKE, CAROLINE; LUCAS, TOBIAS; GROSSMANN, LUCA; CLOSOSKI, GIULIANO CESAR; OPATZ, TILL. Glucose as an Eco-Friendly Reductant in a One-Pot Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. 2020, n. 41, AUG 2020. (18/14150-8)

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)

BORGES, LETICIA DA SILVA; CARVALHO BATISTA, JOAO HENRIQUE; BOZZINI, LEANDRO; LOURENCO JR, CELSO DONIZETE; LOPES, NORBERTO PEPORINE; CLOSOSKI, GIULIANO CESAR; VESSECCHI, RICARDO. Are benzoylium and nitrilium ions produced from substituted 2-arene-2-oxazolines during mass spectrometry? A study based on density functional theory calculations, quantum theory of atoms in molecules, and electrospray ionization tandem mass spectrometry. RAPID COMMUNICATIONS IN MASS SPECTROMETRY, v. 37, n. 4, p. 11-pg., 2023-02-28. (17/04819-5, 09/51812-0, 09/08281-3, 14/50265-3, 20/02207-5, 18/14150-8, 14/23604-1)

CLOSOSKI, GIULIANO C.; SOLDI, RAFAEL A.; DA SILVA, RODRIGO M.; GUARATINI, THAIS; LOPES, JOSE N. C.; PEREIRA, PAMELA R. R.; LOPES, JOAO L. C.; DOS SANTOS, THIAGO; MARTINS, RONALDO B.; COSTA, CRISTINA S.; et al. Tenofovir Disoproxil Fumarate: New Chemical Developments and Encouraging in vitro Biological Results for SARS-CoV-2. Journal of the Brazilian Chemical Society, v. 31, n. 8, p. 1552-1556, AUG 2020. (14/50265-3, 18/14150-8, 14/02438-6)

BERTALLO, CAMILA R. S.; BERLIM, LEONARDO S.; OLIVIER, DANILO S.; ARROIO, THAIS R.; ITO, AMANDO S.; CLOSOSKI, GIULIANO C.. Synthesis and photophysical properties of 2-aryl-5-carbonyl indolizines. DYES AND PIGMENTS, v. 198, FEB 2022. (18/14150-8, 15/03007-1, 18/02855-7, 20/13962-9)

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. (19/05838-9, 18/14150-8, 15/21364-6)

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)

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)

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)

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)

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)

PORTAPILLA, GISELE BULHOES; PEREIRA, LUIZ MIGUEL; SOLDI, RAFAEL AUGUSTO; ABREU FILHO, PERICLES GAMA; GALLO, INARA FERNANDA LAGE; CLOSOSKI, GIULIANO CESAR; DE ALBUQUERQUE, SERGIO. Activity of beta-Caryophyllene Oxide Derivatives Against Trypanosoma cruzi, Mammalian Cells, and Horseradish Peroxidase. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY, v. 30, n. 6, JAN 2021. (12/02105-1, 12/16168-5, 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)

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)

Filed patent(s) as a result of this research project