A First Total Synthesis of Ganglioside HLG‐2

• Published in: Chemistry : a European journal 2009-04, Vol.15 (18), p.4637-4648
• Main Authors: Iwayama, Yuki, Ando, Hiromune, Ishida, Hideharu, Kiso, Makoto
• Format: Article
• Language: English
• Subjects: Animals; Carbohydrate Sequence; Ceramides - chemistry; gangliosides; Gangliosides - chemical synthesis; Gangliosides - chemistry; glycolipids; Holothuria - chemistry; Molecular Sequence Data; natural products; sialic acids; Sialic Acids - chemistry; Stereoisomerism; total synthesis; Trisaccharides - chemistry
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.200802706

A neuritegenic ganglioside from sea cucumber, HLG‐2 (see figure), has been synthesized for the first time. The unique tandem of sialic acids, Neu5Gc‐α(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, α‐N‐glycolylsialyl‐(2,4)‐α‐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. A neuritegenic ganglioside from sea cucumber, HLG‐2 (see figure), has been synthesized for the first time. The unique tandem of sialic acids, Neu5Gc‐α(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.