Syntheses of sugar-related trihydroxyazepanes from simple carbohydrates and their activities as reversible glycosidase inhibitors (original) (raw)
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Helvetica Chimica Acta, 2006
The racemic 2-azabicyclo[3.2.2]nonanes 5 and 18 were synthesized and tested as b-glycosidase inhibitors. The intramolecular Diels-Alder reaction of the masked o-benzoquinone generated from 2-(allyloxy)phenol (6) gave the a-keto acetal 7 which was reduced with SmI 2 to the hydroxy ketone 8. Dihydroxylation, isopropylidenation (! 12), and Beckmann rearrangement provided lactam 15. N-Benzylation of this lactam, reduction to the amine 17, and deprotection provided the amino triol 19 which was debenzylated to the secondary amine 5. Both 5 and 19 proved weak inhibitors of snail b-mannosidase (IC 50 > 10 mM), Caldocellum saccharolyticum b-glucosidase (IC 50 > 10 mM), sweet almond b-glucosidase (IC 50 > 10 mM), yeast a-glucosidase (5: IC 50 > 10 mM; 19: IC 50 = 1.2 mM), and Jack bean a-mannosidase (no inhibition detected).
Synthesis of Pyrrolidine-Based Imino Sugars as Glycosidase Inhibitors
European Journal of Organic Chemistry, 2007
Two pyrrolidine-based imino sugars have been synthesized in an efficient manner, using regiospecific amination, ring closing metathesis, and diastereospecific dihydroxylations as key steps. These azasugars are found to be moderate inhibitors of glycosidases.
Sugar-Derived Di- and Tetrahydropyridazinones: Synthesis of New Glycosidase Inhibitors
Helvetica Chimica Acta, 2000
The N-unsubstituted d-arabino-tetrahydropyridazinone 7 is a micromolar inhibitor of b-glucosidases from sweet almonds (competitive), Caldocellum saccharolyticum (mixed), yeast a-glucosidase (competitive), jack bean a-mannosidase (competitive), and snail b-mannosidase (competitive). The N-substituted tetrahydropyridazinones 22, 24, and 26 are weak inhibitors of these glycosidases, and so are the dihydropyridazinones 8 and 17 ± 19, where the best inhibition was observed for 8 (K i 56 mm for jack bean a-mannosidase). The tetrahydropyridazinones were obtained by reduction of the corresponding dihydropyridazinones with NaCNBH 3 , and the dihydropyridazinones were prepared by treatment with hydrazine or substituted hydrazines of the known and readily available d-threo-pent-2-uluronate 11.