Synthesis of a New Class of N-Linked Lewis and LacNAc Analogues as Potential Inhibitors of Human Fucosyltransferases: A General Method for the Incorporation of an Iminocyclitol as a Transition-State Mimetic of the Donor Sugar to the Acceptor

Abstract

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.