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Updated: May 26, 2026

Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
Synthesis of 5'-terminal capped oligonucleotides using O-N phosphoryl migration of phosphoramidite derivatives
Akihiro Ohkubo1, Nobuhiro Tago, Akira Yokouchi
1Department of Life Science, Tokyo Institute of Technology, Nagatsuta, Midoriku, Yokohama 226-8501, Japan.
Abstract:
Trivalent phosphoramidite derivatives could be readily converted by reacting with 1-hydroxy-7-azabenzotriazole to phosphotriester intermediates; these intermediates reacted smoothly with phosphorylated compounds to give pyrophosphate derivatives. This new phosphorylation approach enabled a facile and rapid synthesis of 5'-adenylated DNA oligomers (A(5')ppDNA) on resins using a silyl-type linker. Our new approach could be applied to the synthesis of a 2'-OMe-RNA oligomer containing the 5'-terminal 2,2,7-trimethylguanosine cap structure.
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