Two-step conversion of uridine and cytidine to variously C5-C functionalized analogs

Abstract

C5-substituted pyrimidine nucleosides are an important class of molecules that have practical use as biological probes and pharmaceuticals. Herein we report an operationally simple protocol for C5-functionalization of uridine and...

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

“…Most of these methods require additional ribose protection and a final step of deprotection, which makes them costly and time‐consuming. Recently, our group reported a straightforward and effective method for the direct trifluoromethylation of uridine and cytidine (Podskoczyj et al., 2023), utilizing a radical approach documented in the literature for the synthesis of CF 3 ‐containing deoxynucleosides (Ito et al., 2017; Ji et al., 2011; Musumeci et al., 2013). Subsequently, 5‐trifluoromethylated uridine (5‐CF 3 U) and cytidine (5‐CF 3 C) were converted to the C5‐carboxyl, ester, cyano, amide, or amidine functionalized derivatives (Podskoczyj et al., 2023).…”

“…This article describes the two‐step approach to introduce several chemically diverse substituents at the C5 position of uridine and cytidine via CF 3 ‐functionalized derivatives (Podskoczyj et al., 2023). Basic Protocol 1 describes the synthesis and purification of 5‐CF 3 U and 5‐CF 3 C. Basic Protocol 2 outlines the conversions of trifluoromethylated uridine and cytidine ( 2a and 2b ) using oxygen and nitrogen nucleophiles.…”

Synthesis of fluorescent 5-heteroarylpyrimidine-containing oligonucleotides via post-synthetic trifluoromethyl conversion

“…32,33 Leszczynska et al also applied this 5-CF 3 conversion for the synthesis of C5-modified pyrimidine ribonucleosides. 36,37 Concerning the CF 3 group conversion, it has been reported that the CF 3 group on the aromatic ring can be converted into nitrogen-containing heterocycles. 38 Inspired by this report and our research interest in expanding the usefulness of 5-CF 3 -pyrimidine bases as a post-synthetic precursor, in this study, we report the preparation of DNA ONs containing 5-(benzimida-zol-2-yl)-and 5-(benzothiazol-2-yl)-pyrimidine bases by postsynthetic method (Scheme 1c).…”