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

A 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 (CF 3 SO 2 Na) in the presence of tert-butyl hydroperoxide and subsequent transformation of the CF 3 group to the C5-C 'carbon substituents' under alkaline conditions. © 2024 Wiley Periodicals LLC. Basic Protocol 1: Synthesis and characterization of 5-trifluoromethyluridine (5-CF 3 U) and 5-trifluoromethylcytidine (5-CF 3 C) Basic Protocol 2: Conversion of 5-CF 3 U and 5-CF 3 C to several C5-substituted ribonucleosides.