Síntese de 4-aril-3-bromo-5-arilidenofuran-2(5H)-onas análogas aos rubrolídeos

• Ano de defesa: 2009
• Autor(a) principal: Barcelos, Rosimeire Coura
• Orientador(a): Maltha, Célia Regina álvares
• Banca de defesa: Teixeira, Róbson Ricardo , Conceição, Gelson José Andrade da , Fernandes, Sergio Antônio
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Viçosa
• Programa de Pós-Graduação: Mestrado em Agroquímica
• Departamento: Agroquímica analítica; Agroquímica inorgânica e Físico-química; Agroquímica orgânica
• País: BR
• Palavras-chave em Português: γ-alquilidenobutenolídeos; Rubrolídeos; Acoplamento de Suzuki
• Palavras-chave em Inglês: γ-alkylidenebutenolides; Rubrolides; Suzuki coupling
• Área do conhecimento CNPq: CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA
• Link de acesso: http://locus.ufv.br/handle/123456789/2144

The γ-alkylidenebutenolides comprise a class of natural products presenting a variety of biological activities. Within this class of substances, there are the rubrolides, lactones isolated from marine ascidians, which are recognized as a source of natural bioactive compounds. Rubrolides are known for its antibiotic, cytotoxic and anti-inflammatory activities. In order to contribute for the knowledge concerning the biological activities of this class of compounds, the present investigation was aimed to synthesize novel arylidenefuranones analogues to rubrolides, and evaluate their phytototoxic and cytotoxic activities. The synthetic route for the preparation of these arylidenefuranones had the mucobromic acid as the starting material which was reduced to 3,4- ibromofuran-2(5H)-one in the presence of sodium borohydrate and methanol in acidic medium. After recrystallization, this brominated furanone was obtained as a white crystalline solid with 80% yield. Afterwards, this lactone was submitted to Suzuki coupling reactions with arylboronic acids. The catalytic system was composed by bis(acetonitrile)dichloropalladium(II), triphenylarsine and silver(II) oxide. Subsequent purification of the crude reaction mixture by column chromatography afforded the lactones 3-bromo-4-(4-fluoro-2- metoxyphenyl)furan-2(5H)-one and 3-bromo-4-(2-fluoro-2-metoxyphenyl)furan-(5H)-one in 76% and 77% yield, respectively. Reaction of these furanones with various substituted aromatic aldehydes in the presence of tert- utyldimethylsilyltrifluoromethanesulfonate and diisopropylethylamine gave the corresponding aldolic adducts which were not isolated. The adducts were subsequently treated with DBU under refluxing conditions. Thus, seven novel rubrolides analogues were synthesized namely 5(Z)-3-bromo-4-(4-fluoro-2- etoxyphenyl)-5-(3,4-methylenedioxibenzylidene) furan-2(5H)-one (79%), 5(Z)-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one(16%), 5(Z)-3-bromo-4-(4-fluoro-2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (30%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(3,4-methylenedioxibenzylidene)furan-2(5H)-one (54%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-nitrobenzylidene)furan-2(5H)-one (41%), 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-(4-trifluoromethylbenzylidene)furan-2(5H)-one (42%) and 5(Z)-3-bromo-4-(2-metoxyphenyl)-5-benzylidenefuran-2(5H)-one (32%). The stereochemistry of the exocyclic double bond was confirmed by X-ray crystallography. Computational calculations were carried out and assisted in the rationalization of the stereochemical outcome of the alkylidenation reactions.