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 beta-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 alpha(2-8)-linkage between two neuraminic acid residues. Removal of the phenylthio group gave intermediate 13, which was transformed into O-tetraosyl 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.
Castro-Palomino
J C
JC
Fachbereich Chemie, Universität Konstanz, Germany.
Simon
B
B
Speer
O
O
Leist
M
M
Schmidt
R R
RR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000166:cytology; D002240:Carbohydrate Sequence; D002417:Cattle; D019069:Cell Respiration / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D005732:Gangliosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D008969:Molecular Sequence Data; D009836:Oligodendroglia / Q000187:drug effects* / Q000648:ultrastructure; D051381:Rats
D005732:Gangliosides; C033851:ganglioside, GD1b; C026226:ganglioside, GD3; D016572:Cyclosporine