Abstract:
Lewis
X (Le
X) is a branched
trisaccharide Galβ1→4(Fucα1→3)GlcNAc that is expressed on many cell surface
glycoproteins and plays critical roles in innate and adaptive immune responses. However, efficient synthesis of
glycopeptides bearing Le
X remains a major limitation for structure-function studies of the Le
X determinant. Here we report a total synthesis of a Le
X pentasaccharide
1 using a regioselective 1-benzenesulfinyl piperidine/triflic anhydride promoted [3 + 2]
glycosylation. The presence of an Fmoc-threonine amino acid facilitates incorporation of the pentasaccharide in
solid phase peptide synthesis, providing a route to diverse
O-linked Le
X glycopeptides. The described approach is broadly applicable to the synthesis of a variety of complex glycopeptides containing
O-linked Le
X or sialyl Lewis
X (sLe
X).
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