SYNTHESIS OF A NEW CLASS OF N-LINKED LEWIS AND LACNAC ANALOGUES AS POTENTIAL INHIBITORS OF HUMAN FUCOSYLTRANSFERASES : A GENERAL METHOD FOR THE INCORP ORATION OF AN IMINOCYCLITOL AS A TRANSITION-STATE MIMETIC OF THE DONOR SUGA R TO THE ACCEPTOR

A short and effective synthesis of N-linked di- and trisaccharides is described. In a high-yielding reaction sequence, the glucosamine derivative 1 was transformed to the 3-azido-2,3-dideoxy sugar 2e under excellent stereocontrol. The LacNAc analogue 4d was synthesized as a single isomer in three steps starting from 2e. In a one-pot procedure, iminocyclitol 5 was transformed into aldehyde 6 and successfully used for reductive amination with 4c and 2f to give trisaccharide 8a and disaccharide 7a, respectively. This procedure represents a general strategy for the incorporation of an iminocyclitol as a transition-state mimic of the donor sugar moiety to the acceptor.