Synthesis of nucleoside 5'-boranophosphorothioate derivatives using an H-boranophosphonate monoester as a precursor.

We developed a method to convert a nucleoside 5'-H-boranophosphonate monoester into the corresponding nucleoside 5'-boranophosphorothioate monoester through temporary protection of the H-boranophosphonate monoester moiety as a diester with 9-fluorenylmethanol, subsequent sulfurization of the P-H group and removal of the 9-fluorenylmethyl group. Although the isolation of the resultant boranophosphorothioate monoester was found to be difficult due to instability of the compound, this new method proved to be useful to synthesize some conjugates of the nucleoside 5'-boranophosphorothioate with other biomolecules, such as cholesterol and an amino acid.