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Updated: Aug 27, 2025

Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
Synthesis of Phosphorodiamidate Oligonucleotide Dimers
Jennifer Albaneze-Walker1, Gregor Urbanietz1, Andras Horvath1
1Chemical Process Research & Development, Janssen Pharmaceutical Companies of Johnson & Johnson, Turnhoutseweg 30, 2340 Beerse, Belgium.
Abstract:
Azido nucleosides couple with phosphoramidites via an initial iminophosphorane, which eliminates acrylonitrile to generate the coupled dimer P(V) product. The vulnerable phosphite triester intermediate is bypassed entirely, making the methodology very suitable to solution-phase synthesis. This new coupling protocol requires no protection of the 5'-OH function and provides a new method of installing internucleosidic phosphorodiamidate bonds with near quantitative yields.
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