Synthesis of alpha- and beta-Galactopyranose-Configured Isomers of Cyclophellitol and Cyclophellitol Aziridine

Cyclophellitol and cyclophellitol aziridine are potent and irreversible mechanism-based inhibitors of retaining -glucosidases. Alterations in the configuration of these compounds can lead to irreversible inhibition of different classes of retaining glycosidases. We have recently reported on the design of a set of -galactopyranose-configured cyclophellitol and cyclophellitol aziridine derivatives that inhibit human retaining -galactosidases. Moreover, we have shown that fluorescently labeled derivatives enable the activity-based profiling of these enzymes in vitro. In this report we describe in detail the synthetic strategies that were used to obtain these epoxide- and aziridine-based probes. In addition, we describe the parallel synthesis of a set of -galactopyranose-configured cyclophellitol isomers as putative inhibitors of retaining beta-galactosidases