Hetero‐Click Conjugation of Oligonucleotides with Glycosides Using Bifunctional Phosphoramidites

Abstract

AbstractTwo phosphoramidite derivatives, 1 and 2, each bearing two orthogonal functions: alkyne/thioacetyl or alkyne/tosyl, respectively, were synthesized and used to generate heteroglyco 5′‐oligonucleotide conjugates. After coupling, the first conjugation was performed using CuAAC on solid support with an azide‐bearing carbohydrate. For 1, the second conjugation was performed in solution by a thiol “click” reaction using a bromoacetamide galactoside, whereas for 2, the tosyl group was converted into an azide and a second CuAAC was applied on solid support. Accordingly, a deoxycholic‐centered heteroglycocluster exhibiting two D‐galactose and two L‐fucose motifs, conjugated to an oligonucleotide, was successfully synthesized.