Nucleoside und Nucleotide. Teil 8. Synthese von Dinucleotiden mit Thymidin und 1‐(2′‐Desoxy‐β‐D‐ribofuranosyl)‐2(1H)‐pyridon als Bausteinen

In order to investigate the stability of 1‐(2′‐deoxy‐β‐D‐ribofuranosyl)‐2(1 H )‐pyridone (Π d , 3 ) under the conditions of oligonucleotide synthesis, the dinucleoside monophosphates (MeOTr)Π d ‐T d ( 9 ) and Π d ‐T d ( 11 ), and the dinucleotides Π d ‐T dp ( 15 ) and pII d ‐T d ( 19 ) were prepared, using various procedures. The N‐glycosidic bond between the deoxyribose and the 2(1 H )‐pyridone proved to be much more labile than the one in the naturally occuring nucleosides. It was partially cleaved in condensation reactions with TPS or MS, but no cleavage was observed when DCC was used. Similarly, the glycosidic linkage was attacked by hot 80% acetic acid, the usual reagent for the removal of a p‐methoxytrityl group in thymidine oligonucleotides. Milder treatment with acetic acid/pyridine 7:3 at 100° removed this protecting group and left the N‐glycoside intact. The compounds prepared were characterized by paper and thin layer chromatography as well as by enzymatic degradation.