The Synthesis of Novel Lewis B and Oncofetal ‘H’ Oligosaccharides for Immunological Studies

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Pickles, Matisse
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University of Guelph

Synthesis of two Lewis B analogues (L-Fuc-α-(1→2)-D-Gal-β-(1→3)[L-Fuc-α-1→4]GlcNAc-β-(1→O)(CH2)6R), where R is representative of an amine or a hydrogen, is described. We initially explored various reaction conditions and donor leaving groups for the creation of the gal-β-(1→3)-GlcNAc glycoside. A D-Gal O-6 benzyl protecting group was vital to the synthesis, however we experienced difficulties retaining this group when creating our bromide donor using known acidic conditions. Thus, we explored novel conditions for the formation of 2,3,4-tri-o-acetyl-6-o-benzyl-1-bromo-α-D-galactoside and found more efficient methods than using HBr. Following synthesis of the Gal-β-(1→3)-GlcNAc glycoside, the desired analogue was generated via difucosylation in 63% yield. The difucosylation also gave a trisaccharide in 20% yield. The trisaccharide was thought to be L-Fuc-α-(1→2)-D-Gal-β-(1→3)[L-Fuc-α-1→4] GlcNAc-β-(1→O)(CH2)6Cl, an analogue of another carbohydrate antigen. NMR analysis, namely ROESY experiments, helped fully elucidate the L-Fuc-α-(1→2)-D-Gal-β-(1→3)[L-Fuc-α-1→4]GlcNAc-β-(1→O)(CH2)6R structure. Aglycone functionalizations and deprotections generated two analogues of Lewis B and two analogues of the ’H’ antigen, respectively.

Lewis B, Oncofetal H antigen, Tumor Associated Carbohydrate Antigen, Chemical synthesis, Synthetic chemistry