Synthesis of Phosphorodiamidate Oligonucleotide Dimers

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.

Automated summary

Azido nucleosides can be coupled with phosphoramidites via an initial iminophosphorane reaction, generating a coupled dimer P(V) product by eliminating acrylonitrile. This method bypasses the susceptible phosphite triester intermediate, making it suitable for solution-phase synthesis. It provides a new approach for installing internucleosidic phosphorodiamidate bonds with nearly quantitative yields, without the need for protection of the 5'-OH function.