Photocatalytic synthesis of 1-pyrrolines under continuous flow conditions and synthesis of pyrrolo[2,1-a]isoquinolines for antiplasmodial evaluation

• Grant number: 23/11454-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: October 01, 2023
• Status: Discontinued
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Arlene Gonçalves Corrêa
• Grantee: Lucas Giani Furniel
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 21/12394-0 - Sustainable synthetic methods employing catalysis, benign solvents, safer reagents, and bio-renewable feedstock, AP.TEM
• Associated scholarship(s): 24/14260-9 - Synthesis of bicyclic N-heterocycles via photochemical formal cycloadditions of cyclopropyl ketones and strained amines, BE.EP.PD

Abstract

Five-membered N-heterocycles are ubiquitous substructures in drugs and biologically active natural products. Pyrrolidines, pyrroles, pyrrolines and gamma-lactams are present in pharmaceuticals such as Doxapram, Brivaracetam, Atorvastatin, Clindamycin and Tolmetin, commonly used as respiratory stimulant, anticonvulsant, for prevention of cardiovascular disease, antibiotic e anti-inflammatory, respectively. The biological importance of this class of compounds has propelled the development of more efficient methodologies for their preparation. Recently, photocatalyzed reactions have emerged as versatile and sustainable strategy for the synthesis polysubstituted N-heterocycles. Hence, the first part of this project aims the study of a photocatalytic reaction involving chalcones and azirines for the synthesis of highly substituted 1-pyrroline derivatives, under flow conditions, that has been developed in our group. Thereafter, it will be studied an asymmetric version of the reaction, which would lead to unprecedented enantioenriched polysubstituted 1-pyrrolines. The second part of this project will focus on the preparation pyrrolo[2,1-a]isoquinolines derivatives, using a copper-catalyzed one-pot conjugate addition/cyclization cascade reaction recently reported by our group. This methodology will also be evaluated as a key step in total synthesis of Lamellarin alkaloids, a class of marine pyrrole alkaloids. These compounds will be further evaluated as antiplasmodial agents.