Synthesis and evaluation of sulfamide-type indolizidines as glycosidase inhibitors

Bioorganic & Medicinal Chemistry Letters
Mahmoud BenltifaAnne Wadouachi

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.

References

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Citations

Dec 18, 2013·Chemical Reviews·William Spillane, Jean-Baptiste Malaubier
Feb 1, 2013·Organic Letters·Richard G CornwallYian Shi
Apr 5, 2016·Chemical Communications : Chem Comm·Elena M Sánchez-FernándezCarmen Ortiz Mellet
Apr 24, 2020·Chemical Communications : Chem Comm·Manuel González-CuestaJosé M García Fernández
Mar 13, 2016·Chemistry : a European Journal·Zachary J GarletsJohn P Wolfe
Aug 11, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elena M Sánchez-FernándezCarmen Ortiz Mellet
Apr 21, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teresa Mena-BarragánCarmen Ortiz Mellet
Jul 18, 2009·Organic Letters·Elena M Sánchez-FernándezJosé M García Fernández
Sep 19, 2014·Journal of the American Chemical Society·David E OlsonJ Du Bois

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