Synthesis, structure, and sugar dynamics of a 2′-spiroisoxazolidine thymidine analog

Bicyclic nucleoside analogs have shown promise in Antisense and RNA interference strategies. Ribofuranosyl ring conformation is a controlling factor in this regard. We have introduced a spiroisoxazolidine ring at the 2′-position of the sugar to gauge the effect it has on sugar dynamics. Proton relaxation measurements and coupling constant analysis indicate the sugar is locked in the North conformation with substantial sugar rigidity evident.