New aspects of glycoside bond formation

Glycoside bond formation generally requires activation of the sugar at the anomeric center. To this end, anomeric oxygen exchange reactions, resulting in the Koenigs-Knorr method and variations or, alternatively, activation t hrough retention of the anomeric oxygen, resulting in the trichloroacetimid ate method and in the phosphite method, have been proposed. The successful application of the trichloroacetimidate method to the total synthesis of GP I anchors is particularly worth mentioning. alpha[2-3]-Sialylation can be b ased on sialyl phosphites as glycosyl donors and on the nitrile effect for anomeric stereocontrol. This is exhibited for a preparative synthesis of ga nglioside GM(2) which is required for tumor vaccine studies. For the genera tion of alpha[2-8]-linkage between neuraminic acid residues anchimeric assi stance by a 3-thiocarbonyloxy group is introduced. The required sialyl dono r can be efficiently prepared and alpha-linkage to 8-O-unprotected neuramin ic acid derivatives is almost quantitative. The limitations of chemical gly copeptide synthesis encourage to employ the protein biosynthesis machinery in combination with an expanded genetic code. This is exhibited for the syn thesis of glycosylated hARF-1 protein.