Ganglioside GQ1b: efficient total synthesis and the expansion to synthetic derivatives to elucidate its biological roles.
The convergent total synthesis of ganglioside GQ1b based on the "cassette approach" between the nonreducing end GQ1b-core heptasaccharide and glucosylceramide building blocks was accomplished in high overall yield. The use of a sialylalpha(2-->8)sialylalpha(2-->3)galactose sequence as the key building block enhanced the efficiency of the glycan assembly and led to preparative-scale synthesis readily applicable for large-scale preparation. In addition, a judicious choice of p-methoxybenzyl protecting groups on glucosylceramide provided a solution to the previous synthetic problems, including a decrease in the yield of the deprotection steps, and led to elevation of the total yield. Furthermore, unnatural-type GQ1b derivatives were synthesized systematically in good yields by capitalizing on a similar approach in order to elucidate their biological roles.
Imamura
Akihiro
A
Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu 501-1193, Japan. aimamura@ualberta.ca
Ando
Hiromune
H
Ishida
Hideharu
H
Kiso
Makoto
M
D002240:Carbohydrate Sequence; D002850:Chromatography, Gel; D018360:Crystallography, X-Ray; D005690:Galactose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D005732:Gangliosides / Q000138:chemical synthesis*; D005963:Glucosylceramides / Q000737:chemistry; D006028:Glycosphingolipids / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D005732:Gangliosides; D005963:Glucosylceramides; D006028:Glycosphingolipids; D009844:Oligosaccharides; C542734:sialylalpha(2-3)galactose; C039129:GQ1b ganglioside; D005690:Galactose