Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5 `-azido residues and 5-octadiynyl side chains

Abstract

Copper(I)-promoted ``click'' cyclization in the presence of TBTA afforded nucleoside macrocycles in very high yields (approximate to 70%) without using protecting groups. To this end, dU and dC derivatives functionalized at the 5-position of the nucleobase with octadiynyl side chains and with azido groups at the 5'-position of the sugar moieties were synthesized. The macrocycles display freely accessible Watson-Crick recognition sites. The conformation of the 16-membered macrocycle was deduced from X-ray analysis and H-1, H-1-NMR coupling constants. The sugar conformation (N vs S) was different in solution as compared to the solid state.