Reações de carbociclização radicalar mediadas por hidreto de tri-n-butilestanho de meta-iodoaliloxibenzamida derivada de D-glicose

• Ano de defesa: 2008
• Autor(a) principal: Grazielli Cristina Batista de Oliveira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Ciclização de radicais arila; Aliloxiiodobenzamidas; Bifenilas; Medicamentos; Síntese orgânica; Química farmacêutica; Farmácia; Compostos orgânicos
• Link de acesso: http://hdl.handle.net/1843/LFSA-7TBMRY

Macrocyclic natural products often display remarkable biological activities. The variety in structure of macrocycles is demonstrated by comparing the drugs cyclosporine, erythromicyn A, vancomycin and amphotericin B. Among macrocycles with biological activities, there are the macrolactams, as vicenistatin, pimecrolimus and others. Many macrolactams are under biological screening, clinical study or already constitute marketed drugs. Although macrocycles synthesis is considered one of the greatest challenges in organic synthesis, the immense chemical diversity and the bioactive potential of these compounds have been stimulating their synthesis investigation. Different synthetic methods have been employed to obtain macrolactams and the tri-n-butyltin hydride-mediated radicalar carbocyclization reactions have been applied to obtain these compounds. In view of the potential applications of macrolactams and the synthetic challenge they present, the research group of Laboratório de Química Farmacêutica/Faculdade de Farmácia/UFMG in partnership with Departamento de Química/ICEx/UFMG (QF/DQ/UFMG) have studied the Bu3SnH-mediated radical cyclizations using unsaturated organohalides as precursor to synthesize macrocycles, especially benzomacrolactams derived from carbohydrate It was found that ortho-iodobenzamides with a carbohydrate unit and an allyloxy group furnish benzomacrolactams with 11-, 12- and 20-membered ring by regioselective endo aryl radical cyclization. The benzamide methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(2-iodobenzoylamino)--D-glucopyranoside furnished a benzomacrolactam by 11-endo cyclization (40%). Carrying on this research program, it was synthesized the meta-iodobenzamide methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(3-iodobenzoylamino)--D-glucopyranoside (9) in eight conventional synthetic steps using methyl -D-glucopyranoside as starting material. The benzamide 9 was undergone to four Bu3SnH-mediated reactions in two different conditions (concentration and addition time). Macrolactams were not isolated from any reaction. These reactions formed hydrogenolysis product together with a surprising biphenyl compound [methyl 4-O-allyl-2,3-di-O-benzyl-6-deoxy-6-(3-penylbenzoylamino)--D-glucopiranoside (13). The structure of this new biphenyl product was elucidated by 1H and 13C NMR spectroscopy, DEPT, COSY, HMQC and HMBC experiments and ESI-MS/MS. A radical addition-elimination process for the formation of 13 and an explanation for the different outcomes for radical reactions of ortho- or meta-allyloxyiodobenzamides are presented.