New Methods for the Formation of the P-N and P-F Bonds, their Relevance to Nucleotide and Oligonucleotide Analogues Synthesis

Abstract

Two approaches have been developed for the formation of phosphoramidates with the nitrogen atom in bridging positions of the internucleotide linkage. One of them makes use of H-phosphonamidates as intermediates and the other is based on the oxidative coupling of H-phosphonate monoesters or their analogues with appropriate amines. Also, a new, convenient entry to nucleoside methylphosphonamidates, consisting of an oxidative coupling of nucleoside 3'-methylphosphinates with 5'-aminonucleosides, was investigated. Finally, iodine promoted desulfurization or deselenization of the appropriate phosphorothioate and phosphoroselenoate diesters in the presence of fluoride anion, was found to provide new means for the formation of the P-F bond.

Keywords::

• Phosphorofluoridates
• Phosphoramidates
• H-Phosphonates