Synthesis of Cyclophellitol, Cyclophellitol Aziridine, and Their Tagged Derivatives

Cyclitol epoxides and aziridines are potent and selective irreversible inhibitors of retaining glycosidases. We have previously reported on our studies on the use of activity-based probes derived from cyclophellitol and from its aziridine analogue for activity-based profiling of retaining -glucosidases in vitro, in situ, and in some examples also in vivo. In this work we disclose full details of the synthesis, purification, and analysis of a comprehensive panel of cyclophellitol analogues, all featuring the -glucose configuration and designed as tools for selective inhibition and/or imaging of human acid glucosylceramidase (epoxides) or as broad-spectrum probes for retaining -glucosidases (aziridines).