Scalable Synthesis of Versatile Rare Deoxyamino Sugar Building Blocks from d -Glucosamine

Abstract

We report the syntheses of 1,3,4-tri-O-acetyl-2-amino-2,6-dideoxy-β-d-glucopyranose and allyl 2-amino-2,6-dideoxy-β-d-glucopyranoside from d-glucosamine hydrochloride. The potential of these two versatile scaffolds as key intermediates to a diversity of orthogonally protected rare deoxyamino hexopyranosides is exemplified in the context of fucosamine, quinovosamine, and bacillosamine. The critical C-6 deoxygenation step to 2,6-dideoxy aminosugars is performed at an early stage on a precursor featuring an imine moiety or a trifluoroacetamide moiety in place of the 2-amino group, respectively. Robustness and scalability are demonstrated for a combination of protecting groups and incremental chemical modifications that sheds light on the promise of the yet unreported allyl 2,6-dideoxy-2-N-trifluoroacetyl-β-d-glucopyranoside when addressing the feasibility of synthetic zwitterionic oligosaccharides. In particular, allyl 3-O-acetyl-4-azido-2,4,6-trideoxy-2-trifluoroacetamido-β-d-galactopyranoside, an advanced 2-acetamido-4-amino-2,4,6-trideoxy-d-galactopyranose building block, was achieved on the 30 g scale from 1,3,4,6-tetra-O-acetyl-β-d-glucosamine hydrochloride in 50% yield and nine steps, albeit only two chromatography purifications.