Protection‐Free, Two‐step Synthesis of C5‐C Functionalized Pyrimidine Nucleosides

Abstract

AbstractA simple, reliable, and efficient method for the gram‐scale chemical synthesis of pyrimidine nucleosides functionalized with C5‐carboxyl, nitrile, ester, amide, or amidine, starting from unprotected uridine and cytidine, is described. The protocol involves the synthesis of 5‐trifluoromethyluridine and 5‐trifluoromethylcytidine with Langlois reagent (CF3SO2Na) in the presence of tert‐butyl hydroperoxide and subsequent transformation of the CF3 group to the C5‐C ‘carbon substituents’ under alkaline conditions. © 2024 Wiley Periodicals LLC.Basic Protocol 1: Synthesis and characterization of 5‐trifluoromethyluridine (5‐CF3U) and 5‐trifluoromethylcytidine (5‐CF3C)Basic Protocol 2: Conversion of 5‐CF3U and 5‐CF3C to several C5‐substituted ribonucleosides