Síntese de cumarinas funcionalizadas por calcogênios via hibridização triazólica e ciclizações eletrofílicas: planejamento molecular e avaliação in silico de potenciais inibidores das colinesterases

• Ano de defesa: 2026
• Autor(a) principal: Ribeiro, Thiago dos Anjos
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Santa Maria; Brasil; UFSM; Programa de Pós-Graduação em Química; Centro de Ciências Naturais e Exatas
• Palavras-chave em Português: Cumarinas; Organocalcogênios; Avaliação in silico; Cicloadição; Síntese orgânica; Coumarins; Organochalcogens; Selenium; Tellurium; Organic synthesis; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA
• Link de acesso: http://repositorio.ufsm.br/handle/1/38871

This work describes the development of synthetic strategies for the preparation of chalcogenfunctionalized coumarins. It highlights derivatives of selenium and tellurium, explores their mechanistic aspects, and discusses their applications in medicinal chemistry. The main objectives were the development of efficient methodologies for functionalizing coumarin nuclei, and the exploration of the structural role of these modifications in the reactivity and biological potential of the obtained molecules. Initially, selenium-containing triazole coumarins were synthesized through copper-catalyzed cycloaddition reactions. In this first work, 10 novel molecules were synthesized with yields ranging from 20% to 99%. Their pharmacological properties were subsequently evaluated using silico tools, such as molecular docking and ADMET parameter prediction. Later, in the second work, a method for the synthesis of chalcogen-functionalized 2,3-dihydrofurocoumarins was developed. In this case, intramolecular electrophilic cyclization reactions were promoted by reactive selenium and tellurium species, generated in situ from the respective diselenides and ditellurides in the presence of Selectfluor®. Under these conditions, 18 novel 2,3-dihydrofurocoumarins were synthesized, with yields ranging from 8% to 87%. The method validation study highlighted the importance of electronic and steric effects associated with aryl substituents. It also showed significant differences in sensitivity between selenium and tellurium to these effects. Taken together, the data demonstrates the viability of the developed methodologies for functionalizing coumarins. They highlight the determining role of the chalcogen in the system's reactivity and advance knowledge in organochalcogen chemistry applied to the synthesis of molecules with pharmacological potential.