RESUMO
1,5-Dideoxy-1,5-iminoalditols of various configurations as well as isofagomine were N-alkylated with non-polar straight chain spacer-arms by a set of simple standard procedures. The spacer-arms' terminal functional groups, primary amines, were employed to introduce fluorescent tags such as dansyl and dapoxyl moieties. Resulting derivatives in the D-xylo, D-gluco, D-galacto as well as GlcNAc series showed distinctly improved glycosidase inhibitory activities compared to parent compounds and are designed to be useful analytical tools.
Assuntos
Inibidores Enzimáticos/síntese química , Corantes Fluorescentes/síntese química , Glucosidases/antagonistas & inibidores , Alquilação , Imino Piranoses/síntese química , Modelos Químicos , Piperidinas/síntese química , Álcoois Açúcares/síntese químicaRESUMO
A range of new C-1 modified derivatives of the powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol has been synthesised and their biological activities probed with the beta-glucosidase from Agrobacterium sp. Ki values are compared with those of previously prepared close relatives. Findings suggest dramatic effects exerted by the aglycon binding site on substrate/inhibitor binding.
Assuntos
Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Manitol/análogos & derivados , Manitol/farmacologia , beta-Glucosidase/química , beta-Glucosidase/metabolismo , Ligação Competitiva , Inibidores Enzimáticos/síntese química , Imino Piranoses , Manitol/síntese química , Manitol/química , Estrutura Molecular , Rhizobium/efeitos dos fármacos , Rhizobium/enzimologia , Relação Estrutura-AtividadeRESUMO
Promotion by Lewis acid of the addition of some aryllithiums to a carbohydrate-based imine, which has allowed a more facile synthesis of some imino-C-nucleoside analogues, is described. Use of the corresponding nitrone does not assist in some cases, but lithiated acetonitrile adds to it efficiently to give a product from which further C-nucleoside analogues can be derived.