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 s teps into sialyl donor 2, which has a phenylthio group on the beta -side of the 3-position for anchimeric assistance and a diethyl phosphite residue a s leaving group at the anomeric carbon. The known GM3 intermediate 10 was t ransformed into the 4b,4c,8c-O-unprotected acceptor 3, which was then allow ed 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 betwe en two neuraminic acid residues. Removal of the phenylthio group gave inter mediate 13, which was transformed into O-tetraosyl trichloroactimate 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-tri ggered uncoupling of mitochondrial respiration and in induction of apoptosi s in oligodendrocytes.