Synthesis of 1,2-cis-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β‑Amino Alcohol Skeletal Rearrangement

The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. The key step to prepare these α-d-GlcNAc and α-d-GalNAc mimics utilizes a β-amino alcohol skeletal rearrangement applied to an azepane precursor. This strategy also allows access to naturally occurring α-HGJ and α-HNJ. The α-d-GlcNAc-configured iminosugar was coupled to a glucoside acceptor to yield a novel pseudodisaccharide. Preliminary glycosidase inhibition evaluation indicates that the α-d-GalNAc-configured homoiminosugar is a potent and selective α-N-acetylgalactosaminidase inhibitor.