Premium
Synthesis of Ganglioside GD3 and its Comparison with Bovine GD3 with Regard to Oligodendrocyte Apoptosis Mitochondrial Damage
Author(s) -
CastroPalomino Julio C.,
Simon Bernadett,
Speer Oliver,
Leist Marcel,
Schmidt Richard R.
Publication year - 2001
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/1521-3765(20010518)7:10<2178::aid-chem2178>3.0.co;2-e
Subject(s) - chemistry , anomer , residue (chemistry) , stereochemistry , sialic acid , tetrasaccharide , neuraminic acid , conjugate , cytochrome c , glycosyl , medicinal chemistry , mitochondrion , biochemistry , polysaccharide , mathematical analysis , mathematics
2,3‐Dehydroneuraminic acid derivative 5 was transformed in five efficient steps into sialyl donor 2 , which has a phenylthio group on the β ‐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 α (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.