Selectin receptors .4. Synthesis of tetrasaccharides sialyl Lewis A and sialyl Lewis X containing a spacer group

Synthesis of two isomeric tetrasaccharides, namely Neu5Ac alpha(2-->3)Gal beta(1-->3)[Fuc alpha(1-->4)]GlcNAc beta (sLe(a)) and Neu5Ac alpha(2-->3)Gal beta(1-->4)[Fuc alpha(1-->3)]GlcNAc beta (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 Le(a) acceptor was accompanied by a variety of undesirable by-processes, namely, N-thioethylation of the GlcNAc residue, beta-sialylation, and lactonisation. In order to improve the yield of sLe(a) tetrasaccharide the glycosylation of Le(a) acceptor by sialyl donors of ethyl and phenyl thioglycoside (promoted by NIS-TfOH or NBS-Bu(4)NBr), 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.