Synthesis of an L-fucose-derived cyclic nitrone and its conversion to alpha-L-fucosidase inhibitors

The L-fuco-nitrone 1 has been synthesized from allyl 4,6-O-benzylidene-alph a-D-glucopyrenoside (4) in 11 steps and an overall yield of 18%. The key st ep is the intramolecular alkylation of an intermediary 1,1-bis(hydroxylamin e) derived from the tosyloxy oximes (E/Z)-2. The nitrone 1 has been transfo rmed into the diamine 30, the indolizidines 39 and 40, the indolizidinones 34 and 35, and the imidazole 44, all inhibiting bovine epididymis a-L-fucos idase with IC50 values between 105 nM and 240 mu M.