Development of selective functionalization of novel heterocycles

• Grant number: 16/24817-4
• Support type: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): April 18, 2017
• Effective date (End): November 25, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal researcher: Flavio da Silva Emery
• Grantee: Paulo Eliandro da Silva Júnior
• Supervisor abroad: Till Opatz
• Home Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Research place: Johannes Gutenberg University Mainz (JGU), Germany
• Associated to the scholarship: 13/26485-0 - Development of new ligands for Peroxisome Proliferator-Activated Receptor by an approach of fragment based drug discovery, BP.DR

Abstract

Chemical space is quite vast, but considering compounds with molecular weight up to 500 Da the number of possibilities is estimated in approximately 1062 compounds, however, only a small fraction of this space is currently exploited for drug discovery process. Within this possibilities, there are a class of compounds that must to be highlighted, the heterocycles, which are structural components commonly found in small bioactive molecules. Inspired by heterocycles as starting point for new compounds obtaining, we have recently developed synthetic routes that access the heterocycles 1 and 2 identified by medicinal chemists at UCB Celltech as 'Heteroaromatic Rings of the Future' that are unexplored starting points for drug discovery applications. These heterocycles represent a complementary pair of nitrogen-rich heterocycles, (À-excessive and À -deficient). Nitrogen-rich heterocyclic compounds have had a profound effect on human health because these chemical motifs are found in a large number of drugs used to combat a broad range of diseases and pathophysiological conditions. Unfortunately, the innate properties of heterocycles that make them so desirable for biological applications them challenging substrates for direct chemical functionalization. In the recent past, radical functionalization of innately reactive heterocycles has re-emerged as an avenue for selective, early or late stage functionalization of pharmaceutically important precursors and products. Considering that, and also the fact of neither of the parent heterocycles 1 and 2 had previously appeared in the medicinal chemistry literature. This project propose to explore the application of radical direct functionalization strategies ( e.g. borono-Minisci reaction, functionalization by zinc sulphinate salts and metal-free direct a-arylation) to the heterocycles 1 and 2, aiming to investigate the incorporation of these heterocycles into drug-like molecules, and identify synthetic methodology that selectively functionalizes these heterocycles at different positions. Due to the novelty of these heterocycles, their reactivity is unknown and we will explore a variety of transformations to identify reagents and conditions that achieve site-specific C-functionalization. (AU)

Scientific publications

(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)

DA SILVA JUNIOR, PAULO ELIANDRO; AMIN, HAWRAZ I. M.; NAUTH, ALEXANDER M.; EMERY, FLAVIO DA SILVA; PROTTI, STEFANO; OPATZ, TILL. Flow Photochemistry of Azosulfones: Application of ``Sunflow{''} Reactors. CHEMPHOTOCHEM, v. 2, n. 10, SI, p. 878-883, OCT 2018. Web of Science Citations: 8.