Synthesis of 7-Chloroquinoline Derivatives Using Mixed Lithium-Magnesium Reagents

Author(s):Show less -

Murie, Valter E. ^[1] ; Nicolino, V, Paula ; dos Santos, Thiago ^[2] ; Gambacorta, Guido ^[3] ; Nishimura, V, Rodolfo H. ; Perovani, Icaro S. ^[4] ; Furtado, Luciana C. ^[5] ; Costa-Lotufo, V, Leticia ; de Oliveira, Anderson Moraes ^[4] ; Vessecchi, Ricardo ^[4] ; Baxendale, Ian R. ^[3] ; Clososki, Giuliano C. ^{[4, 3]}

Affiliation

^[1] V, Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias BioMol, BR-14040903 Ribeirao Preto - Brazil

^[2] Nicolino, Paula, V, V, Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias BioMol, BR-14040903 Ribeirao Preto - Brazil

^[3] Univ Durham, Dept Chem, Durham DH1 3LE - England

^[4] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, BR-14040901 Ribeirao Preto - Brazil

^[5] V, Univ Sao Paulo, Inst Ciencias Biomed, Dept Farmacol, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Organic Chemistry; v. 86, n. 19, p. 13402-13419, OCT 1 2021.
• Web of Science Citations: 0

Abstract

We have prepared a library of functionalized quinolines through the magnesiation of 7-chloroquinolines under mild conditions, employing both batch and continuous flow conditions. The preparation involved the generation of mixed lithium-magnesium intermediates, which were reacted with different electrophiles. Mixed lithium-zinc reagents allowed the synthesis of halogenated and arylated derivatives. Some of the synthesized 4-carbinol quinolines have shown interesting antiproliferative properties, their hydroxyl group being a suitable amino group bioisostere. We also report a two-step approach for optically active derivatives. (AU)

• FAPESP's process: 13/00758-0 - Application of organometallic reagents in the synthesis of new quinoline derivatives with potential antimalarial activity
• Grantee: Paula Valim Nicolino
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 15/21364-6 - Applicantion of Organometallic Reagents in the Directed Functionalization of Quinolines Aimming the Synthesis of Medicinal Interest Compounds
• Grantee: Valter Eduardo Murie
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/05838-9 - Flow modified Lehmstedt-Tanasescu reactions for the scaled production of medicinally important heterocyclic building blocks
• Grantee: Valter Eduardo Murie
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 18/14150-8 - Selective aromatic functionalization: Methodological Studies and new applications in the synthesis of BIOATIVE compounds
• Grantee: Giuliano Cesar Clososki
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/17177-6 - Integrative approach on the sustainable prospection of marine natural products: from diversity to anticancer compounds
• Grantee: Leticia Veras Costa Lotufo
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants