Polymer-supported and chemoenzymatic synthesis of the Neisseria meningitidis pentasaccharide: a methodological comparison Original Research Article

Neisseria meningitidis trisaccharide [GlcNAcβ(1→3)Galβ(1→4)Glc-R], tetrasaccharide [Galβ(1→4)GlcNAcβ(1→3)Galβ(1→4)Glc-R], and a pentasaccharide [Neu5Acα(2→3)Galβ(1→4)GlcNAcβ(1→3)Galβ(1→4)Glc-SPh] were prepared via conventional chemical synthesis, polymer-supported synthesis, and chemoenzymatic methods, starting from d-lactose. The polymer polyethyleneglycol monomethylether (MPEG) and the linker dioxyxylene (DOX) were used with a lactose-bound acceptor to improve the purification process. Several enzymes (LgtA, GalE-LgtB fusion, and CMP-Neu5Ac synthetase/sialyltransferase fusion) were used for syntheses of these oligosaccharides. Excellent stereo- and regioselectivities as well as high yield (>90% from Galβ(1→4)Glc-SPh) of the pentasaccharide were obtained. Both of the convenient processes are suitable for efficient preparation of target oligosaccharides.