Convergent total syntheses of oligosaccharides by one-pot sequential stereoselective glycosylations

A convergent total synthesis of F1alpha antigen, a member of the tumor-associated O-linked mucin glycosyl amino acid, was tried by one-pot sequential glycosylation. Highly alpha-selective glycosylation of amino acid 7 with thioglycoside 6 was Successfully carried out by combining trityl trifluoromethanesulfonate (TrOTf) and N-iodosuccimide (NIS) which gave glycosyl amino acid 21 in high yield (97%, alpha/beta = 83/17). Next, the glycosylation of thioglycoside 4 with galactosyl phenyl carbonate 2 or fluoride 3 was tried by the promotion of trityl tetrakis(pentafluorophenyl)borate [TrB(C6F5)(4)] or trifluoromethanesulfonic acid (TfOH); protected F1alpha 25 was afforded in 80 or 89% overall yield, respectively, by the further addition of glycosyl amino acid 5 and NIS. The desired trisaccharide was obtained in high yield after removal of the protecting groups. Next, a convergent total synthesis of branched hepta-beta-glucoside 30 having phytoalexin-elicitor activity was efficiently performed by way of two one-pot sequential glycosylation reactions: that is, trisaccharide 34 was synthesized in high yield by TfOH-catalyzed one-pot glycosylation using three given monosaccharides (31, 35, and 36) as shown in Scheme 12 and by subsequent selective deprotection of 6'-O-TBDPS group. The second one-pot glycosylation of trisaccharide 34 with three monosaccharides (31, 32, and 33d) also proceeded smoothly to afford heptaglucoside 43 stereo selectively in 48% total yield based oil monosaccharide 32. Phytoalexin-elicitor active branched hepta-beta-glucoside 30 was afforded by the sequential deprotection.