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

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 leav- ing group at the anomeric carbon. The known GM3 intermediate 10 was trans- formed 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 intermedi- ate 13, which was transformed into O- tetraosyl trichloroacetimidate 16 as gly- cosyl donor. Application of the azido- sphingosine glycosylation procedure fur- nished GD3 (1) in high overall yield. Comparison of synthetic GD3 with bo- vine-brain-derived GD3 showed that there were similar effects in GD3-trig- gered uncoupling of mitochondrial res- piration and in induction of apoptosis in oligodendrocytes.