A high yielding chemical synthesis of sialyl Lewis x tetrasaccharide and Lewis x trisaccharide; Examples of regio- and stereodifferentiated glycosylations

Virtually complete regioselective galactosylation of the diol acceptor p-methoxyphenyl 6-O-benzyl-2-deoxy-2-tetrachlorophthalimido-beta-n-glucopyranoside (8) with the donor phenyl 2,3,4-tri-O-acetyl-6-O-benzyl-1-thio-beta-D-galactopyranoside (11) gave the lactosamine derivative 14, which was fucosylated with the donor 15 to give the Le(x) trisaccharide glycoside 2 after deprotection. Regioselective sialylation of the partially protected Le(x) trisaccharide triol 24 with the sialyl donor 25 gave, after deprotection, the SLe(x) tetrasaccharide glycoside 1. The overall yields of 2 and 1 from the monosaccharide starting materials 8, 11, 15, and 25 were 56% and 29%, respectively. In contrast to the virtually complete regio- and stereoselective galactosylation of 8, fucosylation with the benzyl-protected donor 15 gave the corresponding 1-->3- and 1-->4-linked disaccharides in a ratio of 3.6:1 (highly stereo- but not regioselective glycosylation), whereas fucosylation with acetyl-protected donor 18 gave a 2.2:1 beta/alpha-mixture of 4-O-linked disaccharides (highly regio- but not stereoselective glycosylation).