Model Studies Toward the Synthesis of Thymidine Oligonucleotides With Triazole Internucleosidic Linkages via Iterative Cu(I)-Promoted Azide-Alkyne Ligation Chemistry

Given the importance of nonnatural oligodeoxyribonucleotide antisense agents acting as inhibitors of target deleterious genes responsible of 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 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 nonnatural ‘triazole codon’