Functionalized D- and L-Arabino-Pyrrolidines as Potent and Selective Glycosidase Inhibitors

The efficient synthesis of enantiomeric pairs of iminosugars including 1,4-didecov-1,4-imino-D-arabinitol (DAB) and 1,4-dideoxy1,4-imino-L-arabinitol (LAB) analogues with an amidine, hydrazide, hydrazide imide, or amide oxime moiety is described. The preparation of DAB and LAB analogues commenced from L-xylose and D-xylose, respectively. The obtained iminosugars are tested against a panel of glycosidases with pharmaceutical relevance, revealing enhanced activity for the DAB analogues in comparison with the LAB analogues. In particular, the D-arabino-configured amidine behaved as a potent (submicromolar range) and selective inhibitor of alpha-mannosidase.