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.