Generalized anomeric effect in action: synthesis and evaluation of stable reducing indolizidine glycomimetics as glycosidase inhibitors.
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.
Díaz Pérez
V M
VM
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, E-41071, Sevilla, Spain.
García Moreno
M I
MI
Ortiz Mellet
C
C
Fuentes
J
J
Díaz Arribas
J C
JC
Cañada
F J
FJ
García Fernández
J M
JM
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
D004791:Enzyme Inhibitors; D007212:Indolizines; D019163:Reducing Agents; D006026:Glycoside Hydrolases