N -Difluoroacetylhexosamine as a Substrate-Engineering Precursor for Glycosylation Reactions.

We present the application of N -difluoroacetylglucosamine (GlcNDFA) in a chemical evolution strategy to synthesize oligosaccharides. In comparison to conventional N -trifluoroacetylglucosamine, GlcNDFA exhibits superior substrate compatibility with glycosyltransferases as well as stability in aqueous environments. Using our 16-step assembly line, GlcNDFA can be used to produce homogeneous dekaparin, a heparin-like medication, with a yield of 62.2%. This underscores the significant potential of GlcNDFA as a chemical evolution precursor in the precise synthesis of structurally defined polysaccharides.