Efficient Synthesis of Six Tri- to Hexasaccharide Fragments of Shigella flexneri Serotypes 3a and/or X O-Antigen, Including a Study on Acceptors Containing N-Trichloroacetylglucosamine versus N-Acetylglucosamine

Six tri- to hexasaccharide fragments of the {2)-[α-d-Glcp-(1→3)]-α-l-Rhap-(1→2)-α-l-Rhap-(1→3)-[Ac→2]-α-l-Rhap-(1→3)-β-d-GlcpNAc-(1→} n polymer ([(E)AB Ac CD] n ) were synthesized as their propyl glycosides. All targets share the (E)AB sequence. Following a thorough investigation on the use of N-trichloroacetylglucosamine- versus N-acetylglucosamine-containing tri- and tetrasaccharide acceptors, the successful strategy was based on an efficient combination of the trichloroacetimidate chemistry, a trichloroacetyl used as permanent N-protection, and an allyl aglycon as temporary and/or permanent anomeric protection of selected building blocks. Use of an EAB intermediate orthogonally protected at 2A provided both the trisaccharide target and acceptor 12, the condensation of which with a chain terminator D followed by full deprotection, gave tetrasaccharide D(E)AB. Alternatively, stepwise glycosylation of 12 with a D donor compatible with a selective deblocking at position 3D and a 2-O-acetyl C donor following exposure of OH-3D led to a pentasaccharide, which was partially and fully deprotected into free Ac CD(E)AB and CD(E)AB, respectively. Furthermore, chain elongation of the common D(E)AB acceptor with a 2B-O-levulinoyl rhamnobiose donor BC and subsequent partial or total deprotection of the resulting hexasaccharide provided B Ac CD(E)AB and BCD(E)AB, respectively. All of the synthesized oligosaccharides are parts of the O-antigen of Shigella flexneri 3a, a prevalent serotype. Moreover, the non-O-acetylated fragments are also parts of the S. flexneri serotype X O-antigen.