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

• Published in: Carbohydrate research 2000-12, Vol.329 (4), p.755-763
• Main Authors: Kasuya, Maria Carmelita Z, Wang, Lai X, Lee, Yuan C, Mitsuki, Motoaki, Nakajima, Hideki, Miura, Yoshiaki, Sato, Toshinori, Hatanaka, Kenichi, Yamagata, Sadako, Yamagata, Tatsuya
• Format: Article
• Language: English
• Subjects: Animals; Azides - chemical synthesis; Azides - chemistry; Azides - metabolism; Azides - pharmacology; Azido glycoside primer; Biological Transport; Cell Division - drug effects; G(M3) Ganglioside - analogs & derivatives; G(M3) Ganglioside - chemistry; Glycosides - chemical synthesis; Glycosides - chemistry; Glycosides - metabolism; Glycosides - pharmacology; Glycosphingolipids - biosynthesis; Glycosphingolipids - chemistry; Glycosylation; Humans; Lactose - analogs & derivatives; Lactose - chemical synthesis; Lactose - chemistry; Lactose - metabolism; Lactose - pharmacology; Lactosyl ceramide analogue; Melanoma, Experimental; Mice; Molecular Structure; Oligosaccharide library; Oligosaccharides, biocombinatorial synthesis; Saccharide primer, glycosylation; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumor Cells, Cultured
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(00)00238-X

A lactoside primer, 12-azidododecyl β-lactoside, was synthesized via the Koenigs–Knorr method by glycosylation of 1,12-dodecyldiol with perbenzoylated lactosyl bromide. The presence of the 2- O-acyl substituent in the donor gave the β-lactoside, and an excess of acceptor ensured monoglycosylation of the diol. Mesylation of the ω-hydroxyl group in the aglycon, followed by displacement of the mesylate with azide and subsequent O-debenzoylation gave the desired ω-azidododecyl β-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 sialylation of the galactose residue of the primer to give a glycosylated product having the same glycan as in ganglioside GM3. After 24 h incubation of B16 cells with the primers, the amount of sialylated ω-azidododecyl β-lactoside primer was 75% of the amount of sialylated n-dodecyl β-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 than that of the alkyl primer, indicating degradation of the alkyl primer to a larger extent than the ω-azido 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.