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Updated: Jul 5, 2026

Chemical Triphosphorylation of Oligonucleotides
Published on: June 2, 2022
Solution-phase synthesis of di- and trinucleotides using polymer-supported reagents
François Morvan1, Jean-Jacques Vasseur
1Université Montpellier II, Montpellier, France.
Abstract:
A solution-phase phosphoramidite synthesis of short oligonucleotides using solid-supported reagents is described. Polyvinyl pyridinium tosylate is employed as the activator in the coupling step between nucleoside-3'-O-phosphoramidites and 5'-OH nucleosides. The resulting dinucleotide phosphite triesters are oxidized or sulfurized with polymer-bound periodate or tetrathionate to phosphotriesters or thiono phosphotriesters, respectively. Removal of the 3'-O-levulinyl protection is accomplished with a polymer-supported hydrazine. In this approach, the excess reagents are removed by filtration, avoiding complicated purifications. All the polymer-bound reagents used in this method result from salt bridge interactions with the polymers. Consequently, the resins are regenerable.
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