Pseudoamide-type pyrrolidine and pyrrolizidine glycomimetics and their inhibitory activities against glycosidases.
Coupling reaction of (2R,3R,4R,5R)-2,5-hydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) with isothiocyanates afforded the corresponding thiourea adducts, which were transformed into isourea-type bicyclic oxapyrrolizidine glycomimetics by mercury(II) oxide-assisted intramolecular sulfur displacement. Cyclic carbamate and thiocarbamate analogues were also prepared by direct carbonylation or thiocarbonylation of DMDP. Evaluation of the glycosidase inhibitory properties demonstrated that remarkable specificities in enzyme inhibition can be achieved upon modifications on the pseudoaglyconic side chain and on the nature of the sp(2)-hybridized endocyclic ring nitrogen.
García-Moreno
M Isabel
MI
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, E-41071 Sevilla, Spain.
Rodríguez-Lucena
David
D
Mellet
Carmen Ortiz
CO
García Fernández
José M
JM
D000577:Amides / Q000737:chemistry*; D002236:Carbohydrate Conformation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry / Q000494:pharmacology*
D000577:Amides; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D006026:Glycoside Hydrolases