Synthesis and Conformational Analyses of Cyclonucleoside Having 13-Membered Ring Bridging Nucleobase and 5′-Position via a Linker Containing Sulfonamide

Abstract

A cyclic nucleoside has been designed and synthesized to serve as a conformationally fixed building block for the development of functional oligonucleotides. The bridge was introduced between the nucleobase and the 5′-position to fix the rotation around the C4′−C5′ bond, the base orientation, and the sugar puckering all at once. The 13-membered cyclic structure was introduced using a sulfonamide linkage, which retains an N−H group that can be used to attach an additional nucleoside moiety. The sulfonamide linkage was formed through the end-to-end cyclization of an intermediate that contained both a sulfonyltriazole and amino groups. Both 1 H NMR and computational studies revealed that the sugar conformation, base orientation, and γ torsion angle were S-type, anti, and trans, respectively. As such, cyclic nucleosides show promise for introducing these specific distorted conformations into functional nucleic acids.