Efficient Synthesis of Trifluoromethylated Purine Ribonucleosides and Ribonucleotides

Abstract

The protocols presented in this article describe highly detailed synthesis of trifluoromethylated purine nucleotides and nucleosides (G and A). The procedure involves trifluoromethylation of properly protected (acetylated) nucleosides, followed by deprotection leading to key CF₃-containing nucleosides. This gives synthetic access to 8-CF₃-substituted guanosine derivatives and three adenosine derivatives (8-CF₃, 2-CF₃, and 2,8-diCF₃). In further steps, phosphorylation and phosphate elongation (for selected examples) result in respective trifluoromethylated nucleoside mono-, di-, and triphosphates. Support protocols are included for compound handling, purification procedures, analytical sample preparation, and analytical techniques used throughout the performance of the basic protocols. © 2020 Wiley Periodicals LLC.

Basic Protocol 1: Synthesis of trifluoromethylated guanosine and adenosine derivatives

Basic Protocol 2: Synthesis of trifluoromethylated guanosine and adenosine monophosphates

Basic Protocol 3: Synthesis of phosphorimidazolides of ^8-CF3GMP and ^8-CF3AMP

Basic Protocol 4: Synthesis of trifluoromethylated guanosine and adenosine oligophosphates

Support Protocol 1: TLC sample preparation and analysis

Support Protocol 2: Purification protocol for Basic Protocol 1

Support Protocol 3: HPLC analysis and preparative HPLC

Support Protocol 4: Ion-exchange chromatography