Síntese de isocumarinas, 3,4-diidroisocumarinas, dibenzoxazepinonas e síntese parcial da (±)-paralicolina A 

• Ano de defesa: 2015
• Autor(a) principal: Keller Guilherme Guimarães
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: 3; Orto-metalação; Rearranjo de Smiles; Paralicolina A; 4-diidroisocumarinas; Dibenzoxazepinonas; Isocumarinas; Química Orgânica; Síntese orgânica; Cumarinas; Compostos aromáticos Síntese; Produtos naturais; Mecanismos de reações organicas
• Link de acesso: http://hdl.handle.net/1843/SFSA-A7EG6T

In the first part of this thesis describes the synthesis of a series of novel derivatives of isocoumarins, using the Castro-Stephens cross coupling with moderate to good yields. Also novel derivatives of 3,4-diidroisocoumarins were obtained by catalytic hydrogenationof the corresponding precursors in moderate to excellent yields. These compounds were evaluated in vitro for their antiproliferative activities. The 3.4-diidroisocoumarin (1.57) was the most active compound of the series, exhibiting a potent antiproliferative activity and highselectivity against breast cancer cells (MCF-7, GI50=0,66 g mL-1).In the second part of the thesis is reported the total synthesis of (±)-paralycolin A (2.7), isolated from the roots of Clusia paralycola. Initially, there was the preparation of raw materials via directed ortho metalation (DoM), which provided a substitution patternrequired for the proposed synthesis. Combining this methodology with the techniques of cross-coupling Suzuki-Miyaura and Heck led to the synthesis of polysubstituted biaryl compounds. Synthetic application of directed remote metalation provided the phenanthrol system. The key step involved the Birch reduction of the phenanthrene ring to a 9,10-dihydrophenanthrene system. In the third and last part, it is reported the development of a methodology for the synthesis of substituted dibenzoxazepinones (3.13), free of metal catalysts using aconvergent process domino SNAr / Smiles / SNAr. Various substrates were evaluated, demonstrating the critical importance of electronic effects of the ring on the process efficiency.