Estudo visando à síntese total da (S)-nuciferina

• Ano de defesa: 2018
• Autor(a) principal: Silva, Tamiris Reissa Cipriano da [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Total synthesis; Benzyne chemistry; Enantioselective hydrogenation; Aporphine alkaloid; (S)-nuciferine; Química de benzino; Síntese total; Hidrogenação enantiosseletiva; (S)-nuciferina; Alcaloide aporfinoide
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6344555; https://repositorio.unifesp.br/handle/11600/52824

Considering bioactive natural products, aporphine alkaloids compose an important class of compounds that acts as dopamine receptor ligands. In addition, some of these alkaloids, among which we stand out (±)-nuciferine, have presented selective blockade of serotonin 5-HT2A receptor, which in therapeutic terms is related to various disorders, including schizophrenia, insomnia, and ischemic heart disease. Furthermore, aporphine alkaloids have other important biological activities, including, for example, anti-HIV and antineoplastic activities. Having in mind the great biological importance of this class of natural products, we have worked in the enantioselective total synthesis of (S)-nuciferine, through a novel approach to obtain chiral aporphine alkaloids, employing in key steps of the synthesis [4 + 2] cycloaddition reaction followed by hydrogen migration, via benzyne chemistry under mild conditions, and enantioselective hydrogenation reaction, using hydrogen in the presence of catalytic amount of noble metal complex (Ru, Rh, and Ir) containing chiral ligand (monodentate and bidentate). Although (S)-nuciferine has not been achieved, the study of enantioselective reduction reactions afforded relevant information about the stability of dehydroaporphine skeletons and allowed the expansion by searching of better conditions to complete the synthesis in the future.