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Article

Synthesis of Asialo GM₁. New Insights in the Application of Sulfonamidoglycosylation in Oligosaccharide Assembly: Subtle Proximity Effects in the Stereochemical Governance of Glycosidation

Supporting Info

Ohyun Kwon^† and Samuel J. Danishefsky*^†^‡

Contribution from the Department of Chemistry, Havemeyer Hall, Columbia University, New York, New York 10027, and Laboratory for Bioorganic Chemistry, The Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, Box 106, New York, New York 10021

J. Am. Chem. Soc., 1998, 120 (7), pp 1588–1599

DOI: 10.1021/ja9724957

Publication Date (Web): February 4, 1998

†

Columbia University.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

‡

The Sloan-Kettering Institute for Cancer Research.

Abstract

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.