Synthesis of C2-symmetric guanidino-sugars as potent inhibitors of glycosidases.
A series of enantiomerically pure C2-Symmetric guanidino-sugars was synthesized from D-mannitol. The first method described involves direct opening of a bis-epoxide by guanidine, whereas the second one deals with a mercury-catalyzed transformation of a cyclic thiourea into a N,N',N"-trisubstituted guanidine as a key step. The biological activity of these compounds towards several glycosidases has been evaluated. One of them (5) was found to selectively inhibit alpha-L-fucosidase of bovin kidney (2.8 microM).
Le Merrer
Y
Y
Université René Descartes, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601 CNRS, Paris, France. yves.le-merrer@biomedicale.univ-paris5.fr
Gauzy
L
L
Gravier-Pelletier
C
C
Depezay
J C
JC
D002241:Carbohydrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D019791:Guanidine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure
D002241:Carbohydrates; D004791:Enzyme Inhibitors; D006026:Glycoside Hydrolases; D019791:Guanidine