Efficiently Synthesizing Lacto‐Ganglio‐Series Gangliosides by Using a Glucosyl Ceramide Cassette Approach: The Total Synthesis of Ganglioside X2

Abstract

The first total synthesis of the hybrid ganglioside X2, which consisted of a highly branched octasaccharide and ceramide moieties, was accomplished by using a glucosyl ceramide cassette approach. With a disaccharyl donor, the heptasaccharide could not be constructed by glycosylation of the C4 hydroxy group of galactose at the reducing end of the pentasaccharide. In contrast, through an alternative approach with two branched glycan units, a GM2-core trisaccharide, and a lacto-ganglio tetrasaccharide, the heptasaccharyl donor could be prepared and subsequently joined with a glucosyl ceramide cassette to afford the protected ganglioside, X2. Finally, global deprotection completed the synthesis, thus affording the pure ganglioside X2.

Guillain–Barré syndrome and anti-ganglioside antibodies: a clinician-scientist’s journey

“…20) We synthesized the minor gangliosides to find autoantibodies in some patients who were misdiagnosed as having ALS. 21,22) …”

Total syntheses of disulphated glycosphingolipid SB1a and the related monosulphated SM1a

“…Each C3 position of the galactose residues should be protected by the different selectively removable protecting groups because they are potential sites to introduce the sulphate group. To date, we have succeeded in the efficient total synthesis of natural gangliosides such as GQ1b, 13 GalNAc-GD1a, 14 GalNAc-GM1b, 15 X2, 16 LLG-3 17 and GAA-7, 18 using the GlcCer cassette approach. 19 This approach has been proven to be able to overcome a long-standing issue in glycolipid synthesis, namely that coupling of the flexible, poor reactive ceramide acceptor and the oligosaccharyl donor results in low yield and loss of the valuable oligosaccharide unit.…”

Design and Synthesis of a Novel Ganglioside Ligand for Influenza A Viruses †

“…It was envisaged that the efficient synthesis of 1 could be achieved using the cassette approach between the non-reducing end of the oligosaccharide and the glucosylceramide, which was recently developed by our group [ 5 , 6 , 7 , 8 , 9 , 10 ]. Furthermore, it was thought that the construction of the non-reducing end of the heptasaccharide moiety, which includes two types of sialoside, Neu5Acα2-3/2-6Gal, should be executed through a convergent synthetic approach.…”