H-Phosphonate oligonucleotides from phosphoramidite chemistry

A novel phosphoramidite methodology allowing the formation of H-phosphonate oligonucleotides was employed to introduce backbone modifications into oligonucleotides. Novel N,N-diisopropylamino-para-methoxybenzylphosphoramidites were prepared and used in a two-step synthesis cycle during the elongation process. The coupling step was directly followed by an acidic treatment performing concomitant deprotection and phosphite deprotection through an Arbuzov reaction to yield an H-phosphonate linkage.