Direct Stereoselective Aziridination of Cyclohexenols with 3-Amino-2-(trifluoromethyl)quinazolin-4(3H)-one in the Synthesis of Cyclitol Aziridine Glycosidase Inhibitors

: Cyclophellitol aziridine and its configurational and functional isomers are powerful covalent inhibitors of retaining glycosidases, and find application in fundamental studies on glycosidases, amongst others in relation to inherited lysosomal storage disorders caused by glycosidase malfunctioning. Few direct and stereoselective aziridination methodologies are known for the synthesis of cyclophellitol aziridines. Herein, we present our studies on the scope of direct 3-amino-2-(trifluoromethyl)quinazolin-4(3H)-one-mediated aziridination on a variety of configurational and functional cyclohexenol isosters. We demonstrate that the aziridination can be directed by an allylic or homoallylic hydroxyl through H-bonding and that steric hindrance plays a key role in the diastereoselectivity of the reaction.