Total Synthesis of Sulfated Glycosphingolipid SM1a, a Kind of Human Epithelial Carcinoma Antigen

A highly efficient and practical total synthesis of the sulfated ganglioside SM1a, a kind of human epithelial carcinoma antigen identified in mammalian kidney, has been accomplished for the first time. The characteristic sequence of SM1a, β-D-Galp-(1→3)-β-D-NHAcGalp-(1→4)-β-D-(3-O-sulfate)-Galp-(1→4)-β-D-Glcp-ceramide was assembled by a [3+2] convergent approach. A key trisaccharide building block was formed from a new galactose acceptor 7 containing a potential sulfated site, GalNHTroc donor 6, and galactose donor 4. The cyclic glucosyl ceramide was glycosylated with trisaccharide trichloroacetimidate 2 to give the protected ganglioside backbone in good yield. Selective sulfonation at the 3-OH of the Gal residue followed by global deprotection gave the target molecule SM1a.