Hydrogen-Bonding-Assisted Exogenous Nucleophilic Reagent Effect for β‑Selective Glycosylation of Rare 3‑Amino Sugars

Challenges for stereoselective
glycosylation of deoxy sugars are
notorious in carbohydrate chemistry. We herein report a novel strategy
for the construction of the less investigated β-glycosidic bonds
of 3,5-trans-3-amino-2,3,6-trideoxy sugars (3,5-trans-3-ADSs), which constitute the core structure of several
biologically important antibiotics. Current protocol leverages a C-3
axial sulfonamide group in 3,5-trans-3-ADSs as a
hydrogen-bond (H-bond) donor and repurposes substoichiometric phosphine
oxide as an exogenous nucleophilic reagent (exNu) to establish an
intramolecular H-bond between the former and the derived α-oxyphosphonium
ion. This pivotal interaction stabilizes the α-face-covered
intermediate to inhibit the formation of the more reactive β-intermediate,
thereby yielding reversed β-selectivity, which is unconventional
for an exNu-mediated glycosylation system. A wide range of substrates
was accommodated, and good to excellent β-selectivities were
ensured by this H-bonding-assisted exNu effect. The robustness of
the current strategy was further attested by the architectural modification
of natural products and drugs containing 3,5-trans-3-ADSs, as well as the synthesis of a trisaccharide unit in avidinorubicin.