Total synthesis of LewisX using a late-stage crystalline intermediate

• A crystalline orthogonally protected LewisX trisaccharide was synthesised.
• Sequential regioselective glycosylation of a GlcNAc acceptor with galactose and fucose donors provided the trisaccharide.
• The efficient total synthesis of LewisX was completed.

Herein, we report on a highly efficient synthesis of a crystalline protected LewisX trisaccharide that was converted to LewisX following global deprotection. The trisaccharide was prepared in a highly convergent synthesis (seven steps, longest linear sequence) and in a 38% overall yield using a strategy that involved the regioselective glycosylation of a GlcNAc acceptor with a galactose thioglycoside donor, followed by fucosylation of the remaining free GlcNAc hydroxyl as key steps. The core trisaccharide also has the potential to be converted to other members of the Type-2 Lewis family of antigens due to the orthogonal nature of the protecting groups employed.

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