Synthesis of Phosphorus-Containing Biomolecules Using Boranophosphates

Abstract

A boranophosphate is a phosphonic acid derivative bearing a borano group on the phosphorus atom. Boranophosphate oligodeoxyribonucleotides (PB-ODNs) are attractive antisense candidates owing to high nuclease resistance and low cytotoxicity. However, the synthesis of PB-DNAs remains challenging by the conventional synthetic methods. In this study, we have developed efficient methods for the synthesis of boranophosphate-containing ODNs including boranophosphate/phosphorothioate/phosphate chimeric ones. Additionally, boranophosphates are useful precursors for the synthesis of phosphorus-containing biomolecules and their P-modified analogs. Specifically, glycosyl boranophosphates are chemically stable, and glycosyl phosphate analogs are obtained in an effective manner via glycosyl boranophosphate intermediates. Moreover, boranophosphate oligonucleotides provide easy access to various P-modified oligonucleotides via acyl phosphite intermediates. This article describes the synthesis of these phosphorus containig biomolecules and their chemically modified analogs.

Graphical Abstract