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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.

Wrodnigg, Tanja M.; Gaderbauer, Walter; Greimel, Peter; Hausler, Herwig; Sprenger, Friedrich K.; Stutz, Arnold E.; Virgona, Chris; Withers, Stephen G.

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 1-aminodeoxyketopyranoses modified at C-5, facilitated by the ring enlargement of the aldofuranose to the ketopyranose as an addnl. driving force. A range of selected chain extended analogs was prepd. by acylation of N-1. Inhibitors obtained exhibit Ki-values with d-glucosidases in the micromolar range. Interestingly, 1-N-acylation resulted in superior inhibitory activities, as did the addn. of a hexyl chain.