SYNTHESIS OF GANGLIOSIDE GM1 CONTAINING A THIOGLYCOSIDIC BOND TO ITS LABELED CERAMIDE(S) - A FACILE SYNTHESIS STARTING FROM NATURAL GANGLIOSIDES

Capitalizing on the readily available ganglioside, GM1, we have devise d a simple synthesis of labeled GM1 analogues with sulfur in place of oxygen in their linkage to the ceramide residue (SGM1). The sugar moie ty of ganglioside GM1 was released by ozonolysis and subsequent alkali ne fragmentation in good yield. During acetylation of the ganglioside sugar, the carboxyl group of the sialic acid residue lactonized with t he 2-hydroxyl group of the inner galactose moiety (galactose II). The resulting sialoyl-II2-lactone of pentadeca-O-acetyl-monosialogangliote traose could be readily transformed into the alpha-glycosyl bromide. S ubsequent treatment of this glycosyl bromide with potassium thioacetat e afforded the sialoyl-II2-lactone of l-1-S-acetyl-1-thio-beta-monosia logangliotetraose. The latter could be condensed with enzoyl-2-dichlor oacetamido-1-iodo-4-octadecen-3-ol in methanolic sodium acetate to aff ord a protected lyso-SGM1 derivative. One-step removal of the protecti ng groups under alkaline conditions gave beta-monosialogangliotetraosy l thiosphingosine. This lyso-SGM1 was converted into labeled analogues of SGM1 using the N-succinimidoyl derivative of radiocarbon-labeled o ctanoic and octadecanoic acid, respectively. Subsequent actions of GM1 -beta-galactosidase, beta-hexosaminidase A, sialidase and again GM1-be ta-galactosidase on these labeled analogues of SGM1 in the presence of taurodeoxycholate produced the respective analogues of GM2, GM3, lact osylceramide and glucosylceramide, respectively. (C) 1997 Elsevier Sci ence Ltd.