SÍNTESE DE NOVOS DERIVADOS DE LAPACHONAS E NOR-LAPACHONAS: VEREDAS À ATIVIDADE FARMACOLÓGICA

• Ano de defesa: 2007
• Autor(a) principal: Silva Júnior, Eufrânio Nunes da
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso embargado
• dARK ID: ark:/87559/0013000000jsh
• Idioma: por
• Instituição de defesa: Programa de Pós-graduação em Química Orgânica; Química Orgânica
• Palavras-chave em Português: Lapachol; Quinona; Triazol; Composto heterocíclico; Naftoquinona Derivados; Lapachona.; Quinone; Triazole; CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA
• Link de acesso: https://app.uff.br/riuff/handle/1/18070

In the present work the reactivity of orto-furan-naphthoquinones, para-furannaphthoquinones and para-piran-naphthoquinones was studied, in order to produce new pharmacological prototype compounds. Eighteen novel naphthoquinones were prepared. The orto-furan-naphthoquinones 3-(2,5-dimethyl-phenylamino)-2,2-dimethyl-2,3- dihydro-naphtho[1,2-b]furan-4,5-dione (64), 3-(4-fluoro-phenylamino)-2,2-dimethyl-2,3- dihydro-naphtho[1,2-b]furan-4,5-dione (65), 3-(3-chloro-phenylamino)-2,2-dimethyl-2,3- dihydro-naphtho[1,2-b]furan-4,5-dione (66), 3-(3-bromo-phenylamino)-2,2-dimethyl-2,3- dihydro-naphtho[1,2-b]furan-4,5-dione (67), 2,2-dimethyl-3-(3-nitro-phenylamino)-2,3- dihydro-naphtho[1,2-b]furan-4,5-dione (68) and 3-(3-fluoro-phenylamino)-2,2-dimethyl- 2,3-dihydro-naphtho[1,2-b]furan-4,5-dione (69) were obtained, starting from the key intermediate 3-bromo-nor-β-lapachone (37). A great number of possibilities was opened with the obtaining the naphthoquinones 3-azido-2,2-dimethyl-2,3-dihydro-naphtho[1,2- b]furan-4,5-dione (79), 4-azido-2,2-dimethyl-3,4-dihydro-2H-benzo[g]chromene-5,10- dione (86) and 3-azido-2,2-dimethyl-2,3-dihydro-naphtho[2,3-b]furan-4,9-dione (93). The orto-furan-naphthoquinones 3-[4-(1-hydroxy-cyclohexyl)-[1,2,3]triazol-1-yl]-2,2- dimethyl-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione (80), 3-[4-(1-hydroxy-1-methylethyl)-[ 1,2,3]triazol-1-yl]-2,2-dimethyl-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione (81), 2,2-dimethyl-3-(4-phenyl-[1,2,3]triazol-1-yl)-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione (82), 3-(4-hydroxymethyl-[1,2,3]triazol-1-yl)-2,2-dimethyl-2,3-dihydro-naphtho[1,2- b]furan-4,5-dione (83), 2,2-dimethyl-3-[4-(tetrahydro-pyran-2-yloxymethyl)-[1,2,3]triazol- 1-yl]-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione (84) and 3-(4-cyclohex-1-enyl- [1,2,3]triazol-1-yl)-2,2-dimethyl-2,3-dihydro-naphtho[1,2-b]furan-4,5-dione (85). The compounds para-furan-naphthoquinones and para-piran-naphthoquinones 2,2- dimethyl-3-phenylamino-2,3-dihydro-naphtho[2,3-b]furan-4,9-dione (70) and 2,2- dimethyl-4-phenylamino-3,4-dihydro-2H-benzo[g]chromene-5,10-dione (72) were obtained in good yields by a similar methodology to that one used for the synthesis of ortonaphthoquinones. The epoxide of the 2,2-dimethyl-2,3-dihydro-naphtho[2,3-b]furan-4,9- dione (28) was obtained in good yield. The results of the anti-cancer activities of naphthoquinones 64, 65, 66, 67, 68, 70, 72, 76, 79, 80, 81, 82 e 83 over human tumor cell lines indicate the potential of these compounds for the treatment of cancer and their anti-trypanocidal activities for the compounds 64, 65, 66, 67, 68, 70, 72, 76, 79, 80, 81, 82, 83 e 85 also indicate for these compounds important pharmacological potencial.