A new method for introducing amidate linkages in oligonucleotides using phosphoramidite chemistry

Cyanoethyl-protected phosphotriester links in oligonucleotides made with standard phosphoramidite chemistry were converted to phosphoramidate linkages during oligonucleotide synthesis on solid support. The cyanoethyl group was removed with piperidine, and the resulting phosphodiester was activated with p-tosyl chloride. An amine nucleophile displaced the tosyl to yield a phosphoramidate linkage.