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.
The glycan moiety of ganglioside HPG-7, isolated from the sea cucumber (Holothuria pervicax), was synthesized for the first time. The characteristic substructure, a trisialic acid sequence embedded in the glycan, was deliberately constructed by utilizing suitably differentiated sialyl units for various synthetic purposes. Finally, a pentasaccharide was successfully delivered as the hexyl glycoside.
Synthesis of tetrasaccharide portion of ganglioside HPG-1 is described. The tetrasaccharide sequence, Fuc-α(1,8)-Neu5Gc-α(2,4)-Neu5Ac-α(2,6)-Glc, was successfully assembled by a linear strategy, in which the 1,5-lactamized sialyl galactose acceptor and the 8-O-Lev-N-Troc-sialic acid donor were exploited as key units.
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