<i>N</i>‑Difluoroacetylhexosamine\nas a Substrate-Engineering Precursor for Glycosylation Reactions

We present the application of <i>N</i>-difluoroacetylglucosamine\n(GlcNDFA) in a chemical evolution strategy to synthesize oligosaccharides.\nIn comparison to conventional <i>N</i>-trifluoroacetylglucosamine,\nGlcNDFA exhibits superior substrate compatibility with glycosyltransferases\nas well as stability in aqueous environments. Using our 16-step assembly\nline, GlcNDFA can be used to produce homogeneous dekaparin, a heparin-like\nmedication, with a yield of 62.2%. This underscores the significant\npotential of GlcNDFA as a chemical evolution precursor in the precise\nsynthesis of structurally defined polysaccharides.