Recently, glycoconjugates, especially gangliosides which contain sialic acid as an essential constituent, have received much attention owing to their important biological functions (2-111. We have had a program in this area, and our efforts resulted in the development of a facile procedure for the cu-stereoselective coupling [12-141 of sialic acid, a-sialyl-(2 + 8)-sialic acid, and a-sialyL(2 + 8)-cu-sialyl-(2 + 8)-sialic acid using their protected methyl or phenyl 2-thioglycoside as the glycosyl donor and the suitably protected sugar acceptors, with dimethyl(methylthio)sulfonium triflate (DMTST) or N-iodosuccinimide (NIS)-trifluoromethanesulfonic acid (TfOH) as the promoter in acetonitrile solution. There are several gangliosides containing the a-sialyL(2 + 8)-sialic acid unit in their molecules. Ganglioside GQlb, which contains two cY-sialyl-(2 + 8)_sialyl residues attached to a gangliotetraosyl ceramide backbone, was first isolated [15] from human brain and characterized [163. Many biological functions of GQlb, such as nerve growth factor (NGF)-like activity [ 171 in some neuroblastoma cell lines, modulation [18] of protein phosphorylation, and terminal differentiation 1191 in cultured mouse keratinocytes, have been demonstrated. As a continuation of our synthetic efforts toward the goal of elucidating the functions of sialoglycoconjugates at the molecular level, we describe herein the first, total synthesis of ganglioside GQlb, which has one of the most complex structures among gangliosides. For the synthesis of the core tetrasialyl-oligosaccharide of GQlb, trisaccharide 7 was selected as the glycosyl acceptor. Compound 7 provides one free hydroxyl group at C-3 of the Gal residue and a 3,4-0-isopropylidene group at the GalNAc residue, which is selectively removable for further glycosylations with methyl [phenyl 5-acetamido-8-O-* Synthetic studies on sialoglycoconjugates, Part 63. For Part 62, see ref 1.