| Abstract
| - Two efficient routes for the rapid assembly of the tumor-associated carbohydrate antigen Globo-Hhexasaccharide 2 by a preactivation based iterative one-pot strategy are reported. The first method involvesthe sequential coupling of four glycosyl building blocks, leading to the desired hexasaccharide in 47%overall yield in one-pot synthesis. Although model studies on constructing the challenging Gal-α-(1−4)-Gal linkage in Gb3 trisaccharide yielded the desired α linkage almost exclusively, a similar approachto assemble the hexasaccharide led to the formation of a significant amount of β anomer. As an alternative,the second synthesis utilized three components in one pot with the Gal-α-(1−4)-Gal linkage preformed,producing the desired hexasaccharide in a similar overall yield as the four component approach. Bothmethods demonstrate that oligosaccharides containing α and β linkages within the same molecule can beconstructed in one pot via a preactivation based approach with higher glyco-assembly efficiencies thanthe automated solid-phase synthesis strategy. Furthermore, because glycosylations can be carried outindependent of anomeric reactivities of donors, it is not necessary to differentiate anomeric reactivitiesof building blocks through extensive protective group adjustment for chemoselective glycosylation. Thisconfers great flexibilities in the building block design, allowing matching of the donor with the acceptor,leading to improved overall yield.
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