Multigram-scale synthesis of an orthogonally protected 2-acetamido-4-amino-2,4,6-trideoxy-d-galactose (AAT) building block

Abstract

Reported is the gram-scale synthesis of tert-butyldiphenylsilyl 4-(N-benzyloxycarbonyl)-amino-2-azido-2,4,6-trideoxy-β-d-galactopyranoside, which represents an orthogonally protected 2,4-diamino-d-fucose building block, a common constituent of various zwitterionic polysaccharides. The building block has been synthesized from d-glucosamine in 19% overall yield over 14 steps, requiring 5 chromatographic purifications. The key step in the synthesis is the introduction of the C-4 amino substituent, which has been accomplished by a one-pot three step procedure, involving regioselective C-3-O-trichloroacetimidate formation, C-4-O-triflation, and intramolecular substitution. The building block can be used as an acceptor and is readily transformed into a donor glycoside.