The `mirror-image' postulate as a guide to the selection and evaluation of pyrrolidines as alpha-L-fucosidase inhibitors

The ability of a series of pyrrolidines to inhibit several glycosidases was investigated. Using Fleet's `mirror-image postulate', it was proposed that enantiomeric derivatives of 1,4-dideoxy-1,4-imino-D-lyxitol (a known alpha-D-galactosidase inhibitor) would show inhibitory activity against alpha-L-fucosidases. Some modest alpha-L-fucosidase inhibitory activity was observed for selected compounds (particularly an aminomethyl pyrrolidine) and it was proposed that better activity could be obtained by modifying the C-2 side chain of the pyrrolidine core. The D-galacto carbamate scaffold also exhibited somewhat selective, albeit modest, alpha-L-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development. (C) 2012 Elsevier Ltd. All rights reserved.