ja9724957_si_001.pdf (773.43 kB)
Synthesis of Asialo GM1. New Insights in the Application of Sulfonamidoglycosylation in Oligosaccharide Assembly: Subtle Proximity Effects in the Stereochemical Governance of Glycosidation
journal contributionposted on 1998-02-04, 00:00 authored by Ohyun Kwon, Samuel J. Danishefsky
The total synthesis of asialo GM1 (1a) has been accomplished. Using related chemistry, the methyl glycoside of the asialo compound (1b) has also been synthesized. These kinds of compounds have been identified as potential ligands for bacterial and viral infection sites. A simpler structure, which has also been identified for its infection attracting structure in the context of glycopeptides and glycolipids (methyl glycoside 2), has also been synthesized. The key common phase in the syntheses involves the sulfonamidoglycosidation reaction which is used to create a β-linkage leading to a galNAc residue joined to the C4 hydroxyl group of a galactose unit either as a monosaccharide (see compound 2) or as C4‘ in the context of a lactosyl moiety. During the course of these studies there was encountered an unusual “proximal hydroxyl” directing effect. Thus, when C4 on the galactose ring of an azaglycosylating donor bears a free hydroxyl (see, for instance, compound 13), β-glycoside formation predominates. When this hydroxyl group is blocked, the process tends in the direction of α-glycoside formation (see compound 32). These findings were explained as arising from a critical intramolecular hydrogen bond between the C4 axial hydroxyl of the galactose donor and its proximal pyranosidal ring oxygen. This interaction stabilizes conformations from which β-glycosidation predominates.