The ‘mirror-image’ postulate as a guide to the selection and evaluation of pyrrolidines as α-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 α-d-galactosidase inhibitor) would show inhibitory activity against α-l-fucosidases. Some modest α-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, α-l-fucosidase inhibitory activity and may prove to be an interesting scaffold for further development.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Fleet’s mirror image postulate used as a guide to predict glycosidase activity. ► Series of pyrrolidines tested as glycosidase inhibitors. ► Modest α-l-fucosidase inhibitory activity observed. ► Fine tuning of scaffold required to increase inhibition of α-l-fucosidase.