The synthesis of azadisaccharides and aminopyrrolidines as potential glycosidase inhibitors

Azadisaccharides e.g. 399 (Figure 1) are known to be potent selective inhibitors of glycosidases and thus have potential as anti-viral, anti-cancer and anti-diabetic agents. We have developed new, efficient, versatile and stereoselective routes to azadisaccharides using non-carbohydrate starting materials. Pinacol methodology has been successfully used to synthesise two (2→6) linked homoaza-O-disaccharides mimics and due to the versatility of the synthetic route, modification has enabled the synthesis of a (2→6) linked homoaza-O-trisaccharide. Complementary to this, RCM (Grubbs catalyst) and stereoselective dihydroxylation (OSO4) has been utilised in the synthesis of (1→6) linked 5-deoxy-pyrrolidine and piperidine homoaza-O- and N- disaccharides as single diastereoisomers. Preliminary biological screening of these compounds has identified 399 as a weak selective inhibitor of naringinase.;Aminopyrrolidines are compounds of great chemical and biochemical interest and are versatile chiral intermediates in the synthesis of compounds of considerable therapeutic value. Three novel diastereomeric 2-hydroxymethyl-3-amino-4-hydroxylpyrrolidines have been synthesised from one key homoallylic carbamate. Using a tethered aminohydroxylation and a regio- and stereoselective intramolecular epoxide opening the novel (2S, 3S, 4R) isomer 488 and (2S, 3S, 4 S) isomer 489 (Figure 2) have been synthesised respectively. Access to a third (2S, 3R, 4R) isomer was also achieved using an unprecedented regioselective intermolecular epoxide opening. Preliminary biological screening of 488 and 489 has identified both as weak inhibitors of beta-galactosidase.