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|Título :||Synthesis and Comparative Glycosidase Inhibitory Properties of Reducing Castanospermine Analogues|
|Autor :||Díaz Pérez, Paula, García Moreno, María Isabel, Ortiz-Mellet, Carmen, García-Fernández, José Manuel|
|Palabras clave :||Carbamates|
|Fecha de publicación :||2-Jun-2005|
|Resumen:||The feasibility of the intramolecular nucleophilic addition of the nitrogen atom in cyclic (thio)carbamates with a pseudo-C-nucleoside structure to the masked carbonyl group in aldose precursors in the synthesis of reducing (i.e., 5-hydroxy)6-oxaindolizidine frameworks is illustrated by the preparation of the 6-epi, 7-epi, 8-epi and 6,8a-di-epi diastereomers of the potent glycosidase inhibitor (+)-castanospermine. In all cases, the increased anomeric effect caused by the high sp2 character of the pseudoamide-type nitrogen atom resulted in the pseudoanomeric hydroxy group being anchored in an axial orientation in aqueous solution, as in the aglycons in α-glycosides. These analogs of the natural alkaloid showed a higher selectivity in the inhibition of α-glucosidases. Structure/glycosidase inhibitory activity studies indicated that inversion of any hydroxy group resulted in a dramatic decrease in the inhibition potency, confirming the critical importance of a correct hydroxylation profile. In the case of (+)-8-epi-6-oxacastanospermine derivatives, with a hydroxylation profile with a structural complementarity to that of D-galactose, a moderate but very selective inhibition of α-galactosidase was observed, supporting the importance of a defined configuration at pseudoanomeric centres for anomeric specificity.|
|Descripción :||11 páginas, 2 figuras, 1 tabla, 4 esquemas.|
|Versión del editor:||http://dx.doi.org/10.1002/ejoc.200500071|
|Citación :||European Journal of Organic Chemistry (14): 2903-2913 (2005)|
|Appears in Collections:||(IIQ) Artículos|
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