Chemoselective Formylation of an Amine-Functionalized Nucleotide Diphosphate Sugar under Diphosphate-Compatible Conditions

We report the synthesis of a nucleotide diphosphate 4-amino sugar and its late-stage, chemoselective formylation to the corresponding formamide under conditions compatible with highly polar and sensitive, diphosphate substrates. Uridine diphosphate-4-deoxy-4-amino-α-L-arabinose (UDP-Ara4N) was prepared via a convergent phosphate coupling strategy. Selective Nformylation was achieved with formyl–pivalic mixed anhydride under Schotten–Baumann conditions, providing UDP-4-deoxy-4formamido-α-L-arabinose (UDP-Ara4FN, 72%). These results demonstrate that despite the presence of multiple nucleophilic functionalities, chemoselective amine functionalization can be achieved on fully deprotected NDP amino sugars, providing a practical approach to accessing functionalized nucleotide sugar analogues.