General synthesis and biological evaluation of alpha-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-alpha-C-glycosides).
A general synthesis of alpha-1-C-substituted derivatives of fagomine (2-deoxynojirimycin-alpha-C-glycosides) by ring-opening reactions of an aziridine with various heteroatomic nucleophiles, including thiol, amine, alcohol, carboxylate and phosphate, is described. The nine-step reaction sequence proceeded in an overall yield of 14-28% from tri-O-benzyl-D-glucal. Biological evaluation of alpha-1-C-substituted derivatives of fagomine, of the 2-deoxy analog of alpha-homonojirimycin 19 and its 1,N-anhydro derivative 22 as glycosidase inhibitors is reported. The glycosyl phosphate mimetic 15k was found to display no inhibitory activity towards glycogen phosphorylase b and phosphoglucomutase.
Goujon
Jean-Yves
JY
Institut de Chimie Organique et Analytique, CNRS, Université d'Orléans, rue de Chartres, BP 6759, 45067 Orléans, France.
Gueyrard
David
D
Compain
Philippe
P
Martin
Olivier R
OR
Ikeda
Kyoko
K
Kato
Atsushi
A
Asano
Naoki
N
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives; D000818:Animals; D001388:Aziridines / Q000138:chemical synthesis / Q000737:chemistry; D002417:Cattle; D003500:Cyclization; D005944:Glucosamine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D050112:Imino Pyranoses; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
D001388:Aziridines; D006027:Glycosides; D050112:Imino Pyranoses; D010880:Piperidines; D017485:1-Deoxynojirimycin; C105643:fagomine; D006026:Glycoside Hydrolases; D005944:Glucosamine; C013626:nojirimycin