Asymmetric synthesis of 3-amino-4-hydroxy-2-(hydroxymethyl) pyrrolidines as potential glycosidase inhibitors

Three diastereoisomers of 3-amino-4-hydroxy-2-(hydroxymethyl) pyrrolidine have been synthesised by a divergent route starting from trans-4-hydroxy-L-proline. Regio- and stereoselective introduction of the 3-amino and 4-hydroxyl functional groups was achieved using either a tethered aminohydroxylation reaction or by employing intra- and intermolecular epoxide-opening strategies. Preliminary biological data indicate that two of these novel amino pyrrolidines are moderate inhibitors of beta-galactosidase.