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Biologically active 1-aminodeoxy and 1-O-alkyl derivatives of the powerful D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol

TitleBiologically active 1-aminodeoxy and 1-O-alkyl derivatives of the powerful D-glucosidase inhibitor 2,5-dideoxy-2,5-imino-D-mannitol
Publication TypeJournal Article
Year of Publication2000
AuthorsWrodnigg, TM, Gaderbauer, W, Greimel, P, Hausler, H, Sprenger, FK, Stutz, AE, Virgona, C, Withers, SG
JournalJOURNAL OF CARBOHYDRATE CHEMISTRY
Volume19
Pagination975-990
ISSN0732-8303
Abstract

By an Amadori rearrangement of easily available 5-azido-5-deoxy-D-glucofuranose with dibenzylamine and subsequent catalytic hydrogenation of the resulting 5-azido-1-(N,N-dibenzyl)amino-1,5-dideoxy-D-fructopyranose 1-amino-1,2,5-trideoxy-2,5-imino-D-mannitol was obtained in only two steps and in excellent overall yield. Likewise, other amines were employed to introduce extended side chains ultimately suitable for attachment of the inhibitor to solid supports. The reported rearrangement reaction is a high yielding, convenient and apparently general entry to I-amino deoxyketopyranoses modified at C-5, facilitated by the ring enlargement of the aldofuranose to the ketopyranose as an additional driving force. A range of selected chain extended analogues was prepared by acylation of N-1. Inhibitors obtained exhibit K-i-values with D-glucosidases in the micromolar range. Interestingly, 1-N-acylation resulted in superior inhibitory activities, as did the addition of a hexyl chain.

DOI10.1080/07328300008544129