Síntese multicomponente de piperidinas densamente funcionalizadas e estudos sobre atividade fungicida

Abstract

Multicomponent synthesis (MCR) constitutes a versatile and efficient methodological approach for the construction of complex molecules, standing out in the preparation of densely functionalized piperidines, which present high relevance in the pharmaceutical field due to their potential as bioactive compounds. In addition, this strategy is aligned with the principles of green chemistry, as it promotes the reduction of waste generation, as well as the decrease in time and resource consumption during the synthetic process. In the present study, a synthetic route was developed aiming at the preparation of the molecule ethyl-(2S,6R)-1,2,5,6- tetrahydro-1,2,6-triphenyl-4-phenylamine-3-pyridine carboxylate and its halogenated derivatives. The target molecule presents pharmacological relevance by incorporating structural features associated with potential biological activities, such as anti-inflammatory, antitumor, and antimicrobial actions. The methodology employed involved the use of benzaldehydes substituted with chlorine and fluorine atoms in different positions, allowing the evaluation of the electronic and steric effects of these substitutions on the biological activity of the compounds, since halogenated groups can positively influence interactions with biological targets. In total, five molecules were synthesized, named AB, B1, B2, B5, and B6, with yields of 78%, 82%, 83%, 81%, and 79%, respectively. All obtained structures were properly characterized by nuclear magnetic resonance spectroscopy (NMR), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC), confirming the formation of the desired products. The antifungal activity of the compounds was evaluated against the phytopathogen Rhizoctonia solani, responsible for significant losses in agricultural crops of great importance to Brazil. Molecules B1, B2, B5, and B6 showed excellent antifungal activity, promoting complete inhibition of fungal growth, with no visible growth observed. In contrast, molecule AB did not show significant antifungal activity. Overall, the results indicate that the insertion of chlorine and fluorine groups into the synthesized structures contributed positively to antifungal activity, highlighting the potential of these molecules as promising candidates for the development of new antifungal agents.