Document Report Card

Basic Information

ID: ALA1145620

Journal: Bioorg Med Chem Lett

Title: Synthesis and evaluation of sulfamide-type indolizidines as glycosidase inhibitors.

Authors: Benltifa M, García Moreno MI, Ortiz Mellet C, García Fernández JM, Wadouachi A.

Abstract: A practical synthesis of reducing sulfamide-derived iminosugar glycomimetics related to the indolizidine glycosidase inhibitor family is reported. The polyhydroxylated bicyclic system was built from readily accessible hexofuranose derivatives through a synthetic scheme that involves 5,6-cyclic sulfamides. Further intramolecular nucleophilic addition of the sulfamide nitrogen atom to the masked aldehyde group of the monosaccharide in the open chain form afforded the target sugar mimics. By starting from d-glucose and d-mannose precursors, 2-aza-3,3-dioxo-3-thiaindolizidine derivatives with hydroxylation profiles that matched those of (+)-castanospermine and 6-epi-(+)-castanospermine were obtained. In vitro screening against a panel of glycosidases evidenced a high selectivity towards alpha-mannosidase.

CiteXplore: 18420407

DOI: 10.1016/j.bmcl.2008.04.004