Azido glycoside primer:a versatile building block for the biocombinatorial synthesis of glycosphingolipid analogues

摘要

A lactoside primer,12-azidododecyl #beta#-lactoside,was synthesized via the Koenigs-Knorr method by glycosylation of 1,12-dodecyldiol with perbenzolyated lactosyl bromide.The presence of the 2-O-acyl substituent in the donor gave the #beta#-lactoside,and an excess of acceptor ensured monoglycosylation f the diol.Mesylation of the #omega#-hydroxyl group in the aglycon,followed by displacement of the mesylate with azide and subsequent O-debenzolyation gave the desired #omega#-azidododecyl #beta#-lactoside.The azido glycoside primer was examined in mouse B16 melanoma cells for its feasibility as a building block for oligosaccharide biosynthesis.Uptake of the azido glycoside primer by B16 cells resulted in the sialyation of the galactose residue of the primer togive a glycosylated product having the same glycan as in ganglioside GM3.After 24 h incubation of B16 cells with the primers,the amount of sialyated #omega#-azidododecyl #beta#-lactoside primer was 75% of the amount of sialyated n-dodecyl #beta#-lactoside.However,after 48 h incubation,both primers gave equal amounts of the sialylated products.Interestingly,the remaining azido glycoside primer after 48 h incubation was 5.6-fold greater thanthat of the alkyl primer,indicating degradation of the alkyl primer to a larger extent than the #omega#-azdio glycoside primer.The facile chemical synthesis and the efficient uptake in cells make the azido glycoside primer a versatile building block for the biocombinatorial synthesis of glycolipid oligosaccharides.