ABSTRACT
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.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Fluorescent Dyes/chemical synthesis , Glucosidases/antagonists & inhibitors , Alkylation , Imino Pyranoses/chemical synthesis , Models, Chemical , Piperidines/chemical synthesis , Sugar Alcohols/chemical synthesisABSTRACT
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.
Subject(s)
Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Mannitol/analogs & derivatives , Mannitol/pharmacology , beta-Glucosidase/chemistry , beta-Glucosidase/metabolism , Binding, Competitive , Enzyme Inhibitors/chemical synthesis , Imino Pyranoses , Mannitol/chemical synthesis , Mannitol/chemistry , Molecular Structure , Rhizobium/drug effects , Rhizobium/enzymology , Structure-Activity RelationshipABSTRACT
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.
