Nucleoside 3′- N, N-Dialkylphosphonamidates as novel nucleotide units for the solution-phase oligonucleotide synthesis

Abstract

Nucleoside 3′-N,N,-diisopropylphosphonamidate building blocks for oligonucleotide synthesis were prepared in high yields from appropriately protected nucleosides by use of chlorobis(N,N,-diisopropylamino)phosphine as a phosphitylating reagent. The 5′-dimethoxytrityl group of the nucleoside 3′-N,N-diisopropylphosphonamidates was removed selectively without cleavage of the P-N bond under mild acidic conditions. It was found that the nucleoside 3′-N,N-diisopropylphosphonamidates were resistant to oxidation with tert-butyl hydroperoxide. Chain elongation using the phosphonamidate building block was attempted both toward 5′- and 3′-directions and trithymidylate was synthesized. Nucleoside 3′-N,N-diisopropylphosphonamidates were found to be potentially useful as 3′-terminal nucleotide units for the solution-phase oligonucleotide synthesis.