title: Generalized anomeric effect in action: synthesis and evaluation of stable reducing indolizidine glycomimetics as glycosidase inhibitors.
abstract: A series of aminoketalic castanospermine analogues incorporating a stereoelectronically anchored axial hydroxy group at the pseudoanomeric stereocenter (C-5) have been synthesized to satisfy the need for glucosidase inhibitors that are highly selective for alpha-glucosidases. The polyhydroxylated bicyclic system was built from readily available hexofuranose derivatives through a synthetic scheme that involved (i) the construction of a five-membered cyclic (thio)carbamate or (thio)urea moiety at the nonreducing end and (ii) the intramolecular nucleophilic addition of the heterocyclic thiocarbamic nitrogen atom to the masked aldehyde group of the monosaccharide. A biological screening of the resulting reducing 2-oxa- and 2-azaindolizidines against several glycosidase enzymes is reported.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, E-41071, Sevilla, Spain.
authors.forename: V M
authors.initials: VM
authors.lastname: Díaz Pérez
authors.forename: M I
authors.initials: MI
authors.lastname: García Moreno
authors.forename: C
authors.initials: C
authors.lastname: Ortiz Mellet
authors.forename: J
authors.initials: J
authors.lastname: Fuentes
authors.forename: J C
authors.initials: JC
authors.lastname: Díaz Arribas
authors.forename: F J
authors.initials: FJ
authors.lastname: Cañada
authors.forename: J M
authors.initials: JM
authors.lastname: García Fernández
mesh_terms: D002236:Carbohydrate Conformation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005069:Evaluation Studies as Topic; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018716:Molecular Mimicry; D019163:Reducing Agents / Q000737:chemistry*; D013057:Spectrum Analysis
chemical_list: D004791:Enzyme Inhibitors; D007212:Indolizines; D019163:Reducing Agents; D006026:Glycoside Hydrolases