Efficient Synthesis of the Lewis A Tandem Repeat

Abstract

The convergent synthesis of the Lewis A (Lea) tandem repeat is described. The Lea tandem repeat is a carbohydrate ligand for a mannose binding protein that shows potent inhibitory activity against carcinoma growth. The Lea unit, {β-d-Gal-(1→3)-[α-l-Fuc-(1→4)]-β-d-GlcNAc}, was synthesized by stereoselective nitrile-assisted β-galactosylation with the phenyl 3-O-allyl-2,4,6-tri-O-benzyl-1-thio-β-galactoside, and ether-assisted α-fucosylation with fucosyl (N-phenyl)trifluoroacetimidate. This common Lea unit was easily converted to an acceptor and donor in high yields, and the stereoselective assembly of the hexasaccharide and dodecasaccharide as the Lea tandem repeat framework was achieved by 2-trichloroacetamido-assisted β-glycosylation and the (N-phenyl)trifluoroacetimidate method.

Keywords

• Lewis A tandem repeat
• convergent synthesis
• sugar-binding protein