Synthesis of lysogangliosides

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Abstract
The synthesis of gangliosides GM3, GM2, GM1 and GD1a solely lacking the fatty acid moiety, and thus called lysogangliosides in analogy to lysophospholipids, is described. Since a selective elmination of the fatty acid residue was not achieved as yet, the gangliosides were first subjected to alkaline hydrolysis. By this procedure the fatty acyl as well as the acetyl groups of the sialic acid residue(s) were completely removed. The acetamido group of the N-acetylgalactosamine moiety of the gangliosides GM2, GM1 and GD1a was very little (.simeq. 10%) hydrolyzed. In a 2 phase system composed of water and ether, the selective protection of the sphingoid amino group was accomplished with a hydrophobic protective group (9-fluorenylmethoxycarbonyl). Lysoganglisoides were obtained after re-N-acetylation of the sialooligosaccharide amino group(s) followed by removal of the protecting group. The overall yield was about 30%. The structures of the lysogangliosides were confirmed by chemical analysis as well as negative ion FAB [fast atomic bombardment] mass spectrometry and 1H NMR spectroscopy. By simple re-N-acylation of lysogangliosides with any labeled fatty acid, labeled gangliosides are now obtainable that are identical with their parent gangliosides except for their labeled fatty acid residue. This was demonstrated by the synthesis of GM1 with a [1-13C]palmitic acid moiety in its ceramide portion. If desired, double-labeled gangliosides may be obtained by use of labeled acetic anhydride in the synthesis of the lysogangliosides.