Synthesis of Ganglioside GD3 and its Comparison with Bovine GD3 with Regard to Oligodendrocyte Apoptosis Mitochondrial Damage

2,3-Dehydroneuraminic acid derivative 5 was transformed in five efficient steps into sialyl donor 2, which has a phenylthio group on the b-side of the 3-position for anchimeric assistance and a diethyl phosphite residue as leaving group at the anomeric carbon. The known GM3 intermediate 10 was transformed into the 4b,4c,8c O-unprotected acceptor 3, which was then allowed to react with 2 by using TMSOTf as catalyst and acetonitrile as solvent to afford the desired tetrasaccharide 12, which has an a(2 ± 8)-linkage between two neuraminic acid residues. Removal of the phenylthio group gave intermediate 13, which was transformed into Otetraosyl trichloroacetimidate 16 as glycosyl donor. Application of the azidosphingosine glycosylation procedure furnished GD3 (1) in high overall yield. Comparison of synthetic GD3 with bovine-brain derived GD3 showed that there were similar effects in GD3-triggered uncoupling of mitochondrial respiration and in induction of apoptosis in oligodendrocytes