Model Studies Toward the Synthesis of Thymidine Oligonucleotides with Triazole Internucleosidic Linkages <i>Via</i> Iterative Cu(I)‐Promoted Azide–Alkyne Ligation Chemistry

Abstract

Abstract Given the importance of non‐natural oligodeoxyribonucleotide antisense agents acting as inhibitors of target deleterious genes responsible for various diseases, a new approach has been explored to oligothymidines in which triazole internucleosidic linkages replace the native phosphodiester groups. The designed approach is based on the repetition of the copper(I)‐catalyzed azide–alkyne cycloaddition as a key ligation process of suitably functionalized thymidine building blocks. The viability of the method has been demonstrated by the preparation of a triazole‐linked trinucleoside, i.e. , a non‐natural “triazole codon”.