Stereocontrolled Construction of 1,2-cis-α-Glycosidic Linkages Using Glycosyl Diphenyl Phosphates and Synthesis of α-Galactosylceramide KRN7000

The development of a general stereoselective method for 1,2-cis-alpha-glycosidations remains an important issue for synthesis in carbohydrate chemistry. Recently, we have achieved a highly stereocontrolled construction of 1,2-cis-alpha-glycosidic linkages using glycosyl diphenyl phosphates as glycosyl donors. The per-O-benzyl-protected glucosyl and galactosyl donors and the 3,4,6-tri-O-acety1-2-azido-2-deoxygalactosyl donor each react with a range of acceptor alcohols in the presence of 0.05-0.2 equiv of HClO4 in dioxane/Et2O (1:1) to afford glycosides in good yields with good to high alpha-selectivities. The synthetic utility of the present glycosidation method was demonstrated by a stereoselective synthesis of the alpha-galactosylceramide KRN7000, an activator of natural killer (NK) T cells through CD1d molecules.