New Metal-Free Route towards Imidazole-Substituted Uridine.

Abstract

Nucleosides with a bi(hetero)aryl nucleobase have unique potential applications as antiviral drugs and molecular probes. The need for transition metal catalysis to synthesize these nucleosides from pre‐functionalized building blocks and the use of nucleobase protection groups results in expensive and tedious syntheses. Herein we report that 5‐imidazolyl‐uracil can be obtained by scalable Van Leusen imidazole synthesis and regioselectively introduced on ribose to obtain the desired nucleoside in a 5 step synthesis (total yield 55 %). The 5‐imidazolyl moiety leads to improved fluorescence properties. The only side‐product formed was characterized by 2D‐NMR and X‐ray crystallography and could be suppressed during synthesis in favor of the desired product.