Research

Our research group main goal is based on the development of new synthetic methodologies to access aromatic and heteroaromatic systems of high pharmaceutical importance. We have concentrated our efforts in the regioselective generation of organometallic intermediates and their application towards diverse electrophiles to furnish high-functionalized molecules. Besides incorporating modern tools and practices in our projects, such as continuous flow, we are also interested in the biological evaluation of the produced libraries, the development of more sustainable synthetic protocols, scalable synthesis of APIs and total synthesis.

Overview of the explored research areas

TMP-based bases such as TMPMgCl.LiCl and TMPZnCl.LiCl have been successfully applied for the regioselective deprotometalation of substrates such as oxazolines, quinazoline, indolizines, quinolines, furans and thiophenes.

Check our selected publications on this area:

  • DE PAULA BUENO, GABRIEL ; DE OLIVEIRA, LUIZ VINÍCIUS SANTOS ; LOURENÇON, GIOVANNA PRETEROTTO ; CATRICALA FERNANDES, VICTOR HUGO ; BOZZINI, LEANDRO ALVES ; CLOSOSKI, GIULIANO CESAR . PEG-400 Mediated N -(Alkyl)Arylation for the Synthesis of Medicinally Relevant 4-Aminoquinazolines. ChemistrySelect, v. 10, p. e202405163, 2025. https://doi.org/10.1002/slct.202405163
  • BOZZINI, LEANDRO A.; SANTOS, THIAGO DOS; 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, p. 1204-1215, 2021. http://dx.doi.org/10.1021/acs.joc.0c02369.
  • NISHIMURA, RODOLFO H. V.; Murie, Valter E.; VESSECCHI, RICARDO; CLOSOSKI, GIULIANO C. Selective Functionalization of Benzo-Fused N -Heterocycles by Using In Situ Trapping Metalations. CHEMISTRYSELECT, v. 5, p. 11106-11111, 2020. http://dx.doi.org/10.1002/s lct.202002589.
  • CLOSOSKI, GIULIANO C.; STEEL, PATRICK G.; BERTALLO, CAMILA R. DE S.; ARROIO, THAÍS R.; VESSECCHI, RICARDO; TOLEDO, MONICA F. Z. J.; SADLER, SCOTT. C-H activation/metalation approaches for the synthesis of indolizine derivatives. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. 2019, p. 5205-5213, 2019. http://dx.doi.org/10.1002/ejoc.201900608.
  • 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, p. 871-880, 2018. http://dx.doi.org/10.1021/acs.joc.7b02855.
  • AMARAL, MÔNICA F. Z. J. ; BAUMGARTNER, AMANDA A. ; VESSECCHI, RICARDO ; Clososki, Giuliano C. Directed Metalation of 1-Ester-Substituted Indolizines: Base/Electrophile-Controlled Regioselective Functionalization. Organic Letters (Print), v. 17, p. 238-241, 2015. https://doi.org/10.1021/ol503288e.
  • DOS SANTOS, FERNANDA ; BATISTA, JOÃO ; VESSECCHI, RICARDO; CLOSOSKI, GIULIANO C. Directed Functionalization of Cyano-Substituted Furans and Thiophenes with TMPMgCl·LiCl. Synlett (Stuttgart), v. 26, p. 2795-2800, 2015. DOI: 10.1055/s-0035-1560586.

Selected publication:

  • MORAES, VITOR TASSARA ; CAIRES, FRANCO JAZON ; DA SILVA-NETO, PEDRO V. ; MENDONÇA, JACQUELINE NAKAU ; FRAGA-SILVA, THAIS F. C. ; FONTANEZI, BIANCA BUENO ; MARCATO, PRISCYLA DANIELY ; DEPERON BONATO, VANIA LUIZA ; SORGI, CARLOS ARTERIO ; BERALDO MORAES, LUIZ ALBERTO ; CLOSOSKI, GIULIANO CESAR . Naphthoquinone derivatives as potential immunomodulators: prospective for COVID-19 treatment. RSC Advances, v. 14, p. 6532-6541, 2024. https://doi.org/10.1039/D3RA08173G.
  • Murie, V. E.; Nicolino, P. V.; dos Santos, T.; Gambacorta, G.; Nishimura, R. H. V.; Perovani, I. S.; Furtado, L. C.; Costa-Lotufo, L. V.; Moraes de Oliveira, A.; Vessecchi, R.; Baxendale, I. R.; CLOSOSKI, GIULIANO C. Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents. J. Org. Chem., 86, 19, 13402–13419, 2021. https://doi.org/10.1021/acs.joc.1c01521.
  • DOS SANTOS, T.; ORENHA, H. P.; MURIE, V.; VESSECCHI, R.; CLOSOSKI, GIULIANO C. Selective Metalation and Functionalization of Fluorinated Nitriles Using 2,2,6,6-Tetramethylpiperidyl Bases. Organic Letters, 23, 19, 7396–7400, 2021. https://pubs.acs.org/doi/10.1021/acs.orglett.1c02572.
  • CLOSOSKI, GIULIANO C.; SOLDI, RAFAEL; DA SILVA, RODRIGO; GUARATINI, THAIS; LOPES, JOSÉ; PEREIRA, PÂMELA; LOPES, JOÃO; DOS SANTOS, THIAGO; MARTINS, RONALDO; COSTA, CRISTINA; DE CARVALHO, ANDRÉIA; DA SILVA, LUIS; ARRUDA, EURICO; LOPES, NORBERTO P. Tenofovir Disoproxil Fumarate: New Chemical Developments and Encouraging in vitro Biological Results for SARS-CoV-2. JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY, v. 1, p. 1, 2020. http://dx.doi.org/10.21577/0103-5053.20200106.
  • DE MELLO, MURILO; DE OLIVEIRA, ANTONIO; DE OLIVEIRA, CAROLINE; ULTRAMARI, MARIAH; GAMA, FERNANDO; MASCARELLO, ALESSANDRA; GUIMARÃES, CRISTIANO; DE FREITAS, MILLER; CUNHA, CARLOS; LOURENÇO, TIAGO; FERREIRA, FERNANDA; LOPES, JOÃO; CLOSOSKI, GIULIANO C. Characterization and in silico Mutagenic Assessment of a New Betahistine Degradation Impurity. JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY, v. 30, p. 1415-1424, 2019. http://dx.doi.org/10.21577/0103-5053.20190037.

Please visit our Publications page to see our latest work.