Constituents of holothuroidea. 10. Isolation and structure of a biologically active ganglioside molecular species from the sea cucumber Holothuria leucospilota

Three ganglioside molecular species, HLG-1 (1), HLG-2 (2), and HLG-3 (3) ha ve been obtained from the lipid fraction of the chloroform/methanol extract of the sea cucumber Holothuria leucospilota. The structures of these gangl iosides have been determined, on the basis of chemical and spectroscopic ev idence, as 1-O-[(N-gly- colyl-alpha -D-neuraminosyl)-(2 -->6)-beta -D-gluco pyranosyl] -ceramide (1), 1-O-[(N-glycolyl-alpha -D-neuraminosyl)-(2 -->4)- (N-acetyl-alpha -D-neuramino syl)-(2 -->6)-beta -D-glucopyranosyl]-ceramid e (2) and 1-O-[alpha -L-fucopyranosyl-(1 --> 11)-(N- glycolyl-alpha -D-neur aminosyl)-(2 -->4)-(N-acetyl-alpha -D-neuraminosyl)-(2 -->6)-beta -D-glucop yranosyl]-ceramide (3). The ceramide moieties were composed of heterogeneou s phytosphingosine, sphingosine and 2-hydroxy fatty acid units. Compounds 2 and 3 represent new ganglioside molecular species. These three ganglioside molecular species showed neuritogenic activity toward the rat pheochromocy toma cell line, PC-12 cell, in the presence of NGF (nerve growth factor).