Synthesis of multiply fluorinated <i>N</i>-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

Multiple fluorination of glycostructures has emerged as an attractive way modulating their protein affinity, metabolic stability, and lipophilicity. Here we described the synthesis a series mono-, di- trifluorinated N -acetyl-?-glucosamine ?-galactosamine analogs. The key intermediates are corresponding multiply fluorinated glucosazide galactosazide thioglycosides prepared from deoxyfluorinated 1,6-anhydro-2-azido-?-?-hexopyranose precursors by ring-opening reaction with phenyl trimethylsilyl sulfide. Nucleophilic deoxyfluorination at C4 C6 DAST, thioglycoside hydrolysis azide/acetamide transformation completed synthesis.