Résumé
By applying the Liebeskind-Srogl cross-coupling reaction to pyrimidine nucleosides, a Pd(0)-catalyzed, Cu(I)-mediated process that effectively couples thioesters and boronic acids to form ketones, we previously described an efficient and easy access to 5'-
-acyl nucleosides. By reduction of the 5'-carbonyl group into a secondary alcohol, we report herein the synthesis of new 5'-
-aryl-5'-
-dimethoxytrityl-3'-
-phosphoramidite building blocks ready to be incorporated into oligonucleotides by automated synthesis. We describe the preparation of two sets of (
)- and (
)-diastereoisomers of 5'-
-phenylthymidine (
) and 5'-
-pyrenylthymidine (
), their conversion to phosphoramidites and incorporation into oligodeoxynucleotides (ODN). We also discuss the challenges faced by the synthesis of
-modified ODN, which required to modify the automated cycle to prevent backbone degradation in subsequent steps. The affinity and specificity of several 5'-
-aryl modified-ODN toward their complementary sequence were studied by UV-melting experiments. While thermal melting analysis failed to differentiate between matched and mismatched pairs, fluorescence measurements demonstrated that pyrenyl-modified ODN can effectively distinguish correct from incorrect base pairs. This highlights their potential use in the detection of genetic mutations through structural changes in DNA duplexes.