First Total Synthesis of Ganglioside GAA-7 from Starfish Asterias amurensis versicolor

The first total synthesis of neuritogenic ganglioside GAA-7 was achieved using the glucosyl ceramide (Glc-Cer) cassette approach. The stereocenter triad within the ceramide moiety of the target molecule was efficiently established from D-lyxose. The assembly of the ceramide moiety was followed by glycosylation with glucosyl donors to give Glc-Cer cassettes, which underwent conjugation with the oligosaccharide moiety, followed by global deprotection. By using the most suitable Glc-Cer cassette, the target molecule was successfully synthesized. In vitro evaluation indicated that the synthesized GAA-7 and its glycan moiety both showed strong neuritogenic activity towards neuron-like rat adrenal pheochromocytoma (PC12) cells in the presence of neurite growth factor.