Efficient Solid-Phase Chemical Synthesis of 5′-Triphosphates of DNA, RNA, and their Analogues

A robust, reproducible, and scalable method for the solid-phase synthesis of 5'-triphosphates of DNA, RNA, and their chemically modified analogues using 5'-H-phosphonate intermediates is described. 5'-Triphosphates of oligonucleotides with varying lengths and sequences containing different 5'-terminal nucleotides, with and without internal sugar-backbone modifications, were efficiently prepared as crude products or further purified by HPLC.