Síntese de galactosídeos de arila inibidores potenciais de trans-sialidase de Trypanosoma Cruzi

Detalhes bibliográficos
Ano de defesa: 2012
Autor(a) principal: Bruno Leonardo Silva
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal de Minas Gerais
UFMG
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://hdl.handle.net/1843/EMCO-936JAQ
Resumo: Trypanosoma cruzi trans-sialidase (TcTS) is a surface enzyme that catalyses the transfer of residues of the monosaccharide sialic acid from host sialoglycoconjugates to the mucins, abundant proteins expressed on the parasite surface. Physiologically TcTs actively participates of the mechanisms of evasion from the immune system, cell invasion and blood cell apoptosis. This enzyme is, therefore, essential for the development of Chagas Disease, and is considered a promising molecular target for drug design. Thus, the aim of the present work was the design and synthesis of D-galactose-derived potential inhibitors of TcTS using strategies of molecular modification, in special molecular simplification. Ten aryl galactosides modified at carbon-3 were synthesized and characterized for evaluation against TcTS by spectrofluorimetry. By using classical carbohydrate chemistry 4-methoxycarbonylphenyl -D-galactopyranoside and 4-methoxycarbonyl-2-nitrophenyl -D-galactopyranoside were prepared. The regioselective 3-O-alkylation of both compounds was then carried out using methyl iodide, tert-butyl bromoacetate and bromoacetonitrile as electrophylic reagents. The regioselectivity was achieved by employing the dibutyltin oxide method, in which cyclic tin complexes are formed and, upon reaction with an alkyl halide, furnish 3-O-alkylated products, in general high yields and selectivity. The alkylated products bearing tert-butoxycarbonylmethyl or cyanomethyl groups were modified in order to obtain derivatives bearing at C-3 a carboxymethyl or a 5-tetrazolylmethyl group.