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)-[alpha-D-Glcp-(1-->3)]-alpha-L-Rhap-(1-->2)-alpha-L-Rhap-(1-->3)-[Ac-->2]-alpha-L-Rhap-(1-->3)-beta-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 2(A) 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 3(D) and a 2-O-acetyl C donor following exposure of OH-3(D) 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 2(B)-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.
Boutet
Julien
J
Institut Pasteur, Unité de Chimie des Biomolécules (URA CNRS 2128), 28 rue du Dr Roux, F-75015 Paris, France.
Guerreiro
Catherine
C
Mulard
Laurence A
LA
D000117:Acetylglucosamine / Q000737:chemistry*; D002240:Carbohydrate Sequence; D017606:Chlorine Compounds / Q000737:chemistry*; D008969:Molecular Sequence Data; D019081:O Antigens / Q000737:chemistry* / Q000276:immunology; D011134:Polysaccharides / Q000737:chemistry* / Q000276:immunology; D012763:Shigella flexneri / Q000737:chemistry* / Q000145:classification
D017606:Chlorine Compounds; D019081:O Antigens; D011134:Polysaccharides; D000117:Acetylglucosamine