Selectin Receptors 4: Synthesis of Tetrasaccharides Sialyl Lewis A and Sialyl Lewis X Containing A Spacer Group^1,2

ABSTRACT

Synthesis of two isomeric tetrasaccharides, namely Neu5Acα(2→3)Galβ(1→3)[Fucα(1→4)GlcNAcβ (sLe^a) and Neu5Acα(2→3)Galβ(1→4)[Fucα(1→3)]GlcNAcβ (sLe^x) as 3-aminopropyl glycosides is described. Preparation of these compounds was performed by sialylation of selectively protected trisaccharides Le^a and Le^x which contain three unsubstituted OH groups at positions 2, 3 and 4 of Gal residue. Glycosylation of Le^x trisaccharide with ethylthio sialoside under promotion by NIS and TfOH in acetonitrile was effective and regio- and stereoselective to give sLe^x derivative in 81% yield. In contrast, sialylation of the Lc^a acceptor was accompanied by a variety of undesirable by-processes, namely. N-thioethylation of the GlcNAc residue, β-sialylation, and lactonisation. In order to improve the yield of sLc^a tetrasaccharide the glycosylation of Le^a acceptor by sialyl donors of ethyl and phenyl thioglycoside (promoted by NIS-TfOH or NBS-Bu₄NBr), xanthate (promotion by NIS-TfOH mixture or MeOTf) and phosphite (promoted by TMSOTf) types was also studied. Among the reactions investigated the glycosylation by phenyl thioglycoside sialoside promoted by NIS-TfOH gives the best yield (39%) of sLe^a tetrasaccharide product.