Titolo della tesi: Synthesis of biologically important heterocyclic compounds via transition metal-catalyzed and SuFEx click reactions
Heterocyclic compounds are a highly important class of organic compounds due to their large number of applications in pharmaceuticals, biology, agrochemicals, industry, biotechnology, and material chemistry. The synthesis of heterocyclic compounds has always been a fundamental topic for chemistry research. Among them, indoles, benzofurans, quinolines, azepines and triazoles play a major role since they are part of many natural products and biologically active compounds. Indeed, recent studies have confirmed the involvement of molecules containing these structural motifs in a diverse array of biological processes, thereby exerting modulatory effects on various cellular actions. In this context, the primary goal of organic and medicinal chemists is to develop novel synthetic strategies for accessing challenging structures and small heterocycles. Among the many known chemical processes, organometallic catalysis, in particular that mediated by palladium, copper and sulfur-fluorine exchange (SuFEx) reactions occupy a place of absolute importance for the following reasons. Palladium (Pd) catalysis represented a huge leap forward in heterocycle chemistry, paving the way toward a variety of compounds, once inaccessible. CuAAC reaction introduced the regioselective synthesis of 1,4-disubstituted 1,2,3-triazole under mild reaction conditions. SuFEx chemistry enables the efficient and selective formation of S-F bonds under mild conditions, facilitating the synthesis of diverse sulfur-containing compounds with high functional group compatibility.
Integrating these synthetic approaches enhances the efficiency and diversity to synthesize biologically relevant compounds. For instance, Pd-catalyzed cross-coupling reactions and C-H or C-X activation can introduce key functional groups, while click chemistry can modularly connect molecular scaffolds. SuFEx chemistry can establish specific functionalities or modify existing groups selectively. Overall, the combination of Pd-catalyzed, click, and SuFEx chemistry provides a powerful toolkit for the synthesis of biologically important moieties, enabling the rapid and efficient generation of diverse chemical libraries for drug discovery and development.
This PhD thesis investigates the synthesis of biologically significant heterocycles, focusing on these advanced methodologies as primary strategies. The research aims to elucidate their utility and efficacy in creating heterocyclic compounds with potential biological relevance, contributing to synthetic chemistry's advancement and novel compound development for drug discovery and biomedical applications.