Use of a temporary protective group during the synthesis of oligonucleotides with an unnatural bond

Methoxygroup has been used for transient P-protection on H-phosphonate oligonucleotide synthesis. Whereas other H-phosphonate linkages can be irreversibly transformed into phosphoramidates by treatment with alkylamines, the protected phosphoralkoxyl groups generate natural phosphodiester linkages after the final deprotection. The method allows for synthesis of oligonucleotides with addressed position of internucleotide phosphoralkylamidate groups.