A facile total synthesis of ganglioside GD2

✍ Scribed by Hideki Ishida; Yasuhiro Ohta; Yoji Tsukada; Yukihiro Isogai; Hideharu Ishida; Makoto Kiso; Akira Hasegawa

• Publisher: Elsevier Science
• Year: 1994
• Tongue: English
• Weight: 605 KB
• Volume: 252
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(94)90023-x

✦ Synopsis

Recently, as more and more biological functions2-9 of gangliosides are being revealed, their stereocontrolled synthesis is urgently required to aid the elucidation of their functions at the molecular level. In particular, a facile systematic synthesis of polysialogangliosides containing the cu-sialyl-(2 -+ 8)-sialic acid unit in their molecules is of interest in connection with the important biological roles of these glycolipids",".

We have developed12-15 an a-stereoselective procedure for glycosylation with sialic acid, a-sialyl-(2 + 8)-sialic acid and a-sialyl-(2 + 8)-a-sialyl-(2 + 8)-sialic acid employing their 2-thioglycosides as glycosyl donors and suitably protected acceptors, with dimethyl(methylthio)sulfonium triflate (DMTST) or N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (or TMS triflate) as glycosylation promoters in acetonitrile, and have synthesized a variety of gangliosides16 and their ana-logues17. In previous reports14, we described the synthesis of ganglioside GD3, in which cr-sialyl-(2 -+ 8)-sialic acid is linked as the cr-glycoside at C-3' of the lactose moiety in the molecule, in a connection with a novel approach to the systematic synthesis of polysialoglycoconjugates.

As a part of our continuing studies on the systematic synthesis and elucidation of the functions of gangliosides, we describe here a facile total synthesis of gangliosides GD2. This ganglioside, which was first isolated from human brain by Kuhn and Wiegandt", is well known as a human melanoma-associated antigen1'P'9.

RESULTS AND DISCUSSlON

Methyl 6-O-benzoyl-2-deoxy-3,4-O-isopropylidene-2-phthalimido-l-thio-~-~-galactopyranoside2' (2) was selected as the glycosyl donor, and compound 1 (ref 14) as the acceptor in the synthesis of GD2.