The total synthesis of ganglioside GP3, which is found in the starfish Asterina pectinifera, has been accomplished through stereoselective and effective glycosylation reactions. The sialic acid embedded octasaccharide moiety of the target compound was constructed by [4+4] convergent coupling. A tetrasaccharyl donor and acceptor that contained internal sialic acid residues were synthesized with an orthogonally protected N-Troc sialic acid donor as the key common synthetic unit, and they underwent highly stereoselective glycosidation. The resulting sialosides were subsequently transformed into reactive glycosyl acceptors. [4+4] coupling furnished the octasaccharide framework in 91 % yield as a single stereoisomer. Final conjugation of the octasaccharyl donor and glucosyl ceramide acceptor produced the protected target compound in high yield, which underwent global deprotection to successfully deliver ganglioside GP3.

The total synthesis of ganglioside PNG-2A from the starfish Protoreaster nodosus and its neuritogenic activity toward neuron-like cells is described. The unique galactose-enriched glycan moiety, in which an 8-O-methyl sialic acid residue is sandwiched between galactose residues, was constructed through an efficient 8-O-methylation and subsequent di-tert-butylsilylene-assisted α-glycosylation at the 4-OH of the sialic acid residue with a Galfβ(1,3)Gal donor. In vitro biological evaluation in a rat adrenal pheochromocytoma (PC12) cell line revealed that the synthesized PNG-2A potentiated the neurite outgrowth of PC12 cells in the presence of nerve growth factor (NGF).

The first total synthesis of the hybrid ganglioside X2, which consisted of a highly branched octasaccharide and ceramide moieties, was accomplished by using a glucosyl ceramide cassette approach. With a disaccharyl donor, the heptasaccharide could not be constructed by glycosylation of the C4 hydroxy group of galactose at the reducing end of the pentasaccharide. In contrast, through an alternative approach with two branched glycan units, a GM2-core trisaccharide, and a lacto-ganglio tetrasaccharide, the heptasaccharyl donor could be prepared and subsequently joined with a glucosyl ceramide cassette to afford the protected ganglioside, X2. Finally, global deprotection completed the synthesis, thus affording the pure ganglioside X2.

The hybrid ganglioside X1, which was identified in the bovine brain, was synthesized for the first time. Ganglioside X1 is believed to be involved in the development of amyotrophic lateral sclerosis-like disorders in patients with neurological disorders after treatment with bovine brain gangliosides. A convergent approach using two branched glycan units, the GM2-core trisaccharide and the lacto-ganglio tetrasaccharide, efficiently provided the highly branched heptasaccharide part of ganglioside X1, which was conjugated with the ceramide part to produce the protected ganglioside X1. Global deprotection delivered homogenous ganglioside X1, with which serum from the patient was reacted.