Copper-Catalyzed Synthesis of Pyrrolo[1,2-c]quinazolines and Pyrrolo[2,1-a]isoquinolines and Antiplasmodial Evaluation

Author(s)

Moreira, Natailia M. ; de Miranda, Ingrid T. ; dos Santos, Jhonathan R. N. ; Opatz, Till ; Oliva, Glaucius ; Guido, Rafael V. C. ; Correa, Arlene G.

• Document type: Journal article
• Source: Journal of Organic Chemistry; v. 88, n. 13, p. 10-pg., 2023-06-05.

Abstract

Reactionsinvolving C(sp(3))-H bonds of azaareneshave been widely studied in recent years as they allow direct functionalizationof these N-heterocycles without the use of harshreaction conditions. In this work, we describe the C(sp(3))-H functionalization of 4-methylquinazolines and 1-benzylisoquinolines,employing alpha-substituted beta-nitrostyrenes catalyzed by inexpensivecopper acetate. Under the optimized condition, 21 pyrrolo[1,2-c]quinazolines, as well as an imidazo[1,2-c]quinazoline and 4 pyrrolo[2,1-a]isoquinolines,were obtained in moderate to good yields. Furthermore, the biologicalactivity of the pyrrolo[1,2-c]quinazolines was evaluatedagainst Plasmodium falciparum, andpromising results were obtained. (AU)

• FAPESP's process: 16/20609-8 - Mult-user equipment approved in the grant 2014/50249-8: ultra-performance liquid chromatography with supercritical CO2 and mass detector
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 17/19940-4 - Synthesis and evaluation of antiparasitic activity of quinazolines employing multicomponent reactions and C-H functionalization
• Grantee: Natália Menezes Moreira Borges
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/12904-5 - Discovery of Plasmodium falciparum inhibitors from Cerrado plants as lead compounds candidates for malaria: integrated studies of ultra-efficient chromatography, spectroscopy, and biological assays
• Grantee: Rafael Victorio Carvalho Guido
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants
• FAPESP's process: 20/10349-4 - Synthesis of fused N-heterocycles employing C-H functionalization reactions and evaluation of antiparasitary activity
• Grantee: Natália Menezes Moreira Borges
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 22/01066-4 - Discovery of natural products isolated from fungal lineages as lead candidates for Malaria
• Grantee: Natália Menezes Moreira Borges
• Support Opportunities: Scholarships in Brazil - Post-Doctoral