“Double-click” protocol for synthesis of heterobifunctional multivalent ligands: Toward a focused library of specific norovirus inhibitors

Researchers synrhesized hetero-bifunctional ligands either presented on a polymeric scaffold or as univalent monomers for STD NMR studies. All derivatives contained an invariant moiety, the α-L-fucose, and differ in the second variable ligand, a non-carbohydrate molecule selected by STD NMR screening of the Maybridge compound library. The detailed account of this screening, which directed he design of the hetero-bifunctional ligands, together with NMR studies of the univalent monomers is reported in the accompanying manuscript. The first compund was was obtained by Fisher glycosidation of lfucose with propargyl alcohol, by using sulfuric acid immobilized on silica as a catalyst. This method provided the desired glycoside in a 4:1 (α/Β) ratio. After peracetylation, the α anomer was easily purified from an (α/Β) mixture of triacetates. Trans-esterification afforded compound 2 in 50% overall yield.