A first total synthesis of ganglioside HLG-2.
A neuritegenic ganglioside from sea cucumber, HLG-2 (see figure), has been synthesized for the first time. The unique tandem of sialic acids, Neu5Gc-alpha(2,4)-NeuAc, was established by the combination of a reactive N-Troc sialyl donor and a 1,5-lactamized sialyl acceptor. The ceramide counterpart was assembled in a stereoselective manner. Direct connection of the trisaccharide and the ceramide successfully afforded a precursor of HLG-2, which was converted to ganglioside HLG-2 in pure form.A first synthesis of the neuritegenic ganglioside HLG-2, which was identified in extracts of the sea cucumber Holothuria leucospilota, is described. The characteristic sequence of the trisaccharide part, alpha-N-glycolylsialyl-(2,4)-alpha-N-acetylsialyl-(2,6)-glucoside, was efficiently assembled by coupling of a highly active N-2,2,2-trichloroethoxycarbonyl (Troc)-protected sialyl donor and a 1,5-lactamized sialyl acceptor with high stereoselectivity. The corresponding trisaccharyl imidate donor was directly glycosidated with the primary hydroxyl group of the ceramide part, producing protected HLG-2 in relatively high yield, global deprotection of which furnished ganglioside HLG-2 in highly pure form.
Iwayama
Yuki
Y
Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, Japan.
Ando
Hiromune
H
Ishida
Hideharu
H
Kiso
Makoto
M
D000818:Animals; D002240:Carbohydrate Sequence; D002518:Ceramides / Q000737:chemistry; D005732:Gangliosides / Q000138:chemical synthesis* / Q000737:chemistry; D047332:Holothuria / Q000737:chemistry; D008969:Molecular Sequence Data; D012794:Sialic Acids / Q000737:chemistry; D013237:Stereoisomerism; D014312:Trisaccharides / Q000737:chemistry
C432904:1-O-((N-glycolylneuraminosyl)-(2-4)-(N-acetylneuraminosyl)-(2-6)glucopyranosyl)ceramide; D002518:Ceramides; D005732:Gangliosides; D012794:Sialic Acids; D014312:Trisaccharides