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

Yves Blériot (1) , Nicolas Auberger (1) , Jagadeesh Yerri (1) , Charles Gauthier (1) , Giuseppe Prencipe (1) , Anh Tuan Tran (1) , Jerome Marrot (2, 1) , Jerome Desire (1) , Arisa Yamamoto (3, 1) , Atsushi Kato (3, 1) , Matthieu Sollogoub (1)

1 IC2MP [Poitiers] - Institut de chimie des milieux et matériaux de Poitiers [UMR 7285]
2 ILV - Institut Lavoisier de Versailles
3 Department of Hospital Pharmacy [Toyama]

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

Domaines: Chimie; Chimie organique

Yves Blériot, Nicolas Auberger, Jagadeesh Yerri, Charles Gauthier, Giuseppe Prencipe, et al.. Synthesis of 1,2-cis-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β-Amino Alcohol Skeletal Rearrangement. Organic Letters, 2014, 16 (21 ), pp.5512-5515. ⟨10.1021/ol502926f⟩. ⟨hal-01315083⟩