A practical synthesis of nucleoside 5′-diphosphates from nucleoside 5′-H-phosphonate monoesters

Abstract

A simple and convenient synthetic protocols based on H-phosphonate chemistry have been developed for the preparation of nucleoside 5′-diphosphates. It consists of oxidation of the silylated H-phosphonate monoesters in pyridine with iodine to produce the corresponding N-pyridiniumphosphonate intermediates, followed by their reactions with orthophosphoric acid used as a nucleophile. The added value of the method is that substrates for the reaction, H-phosphonate monoesters, can be prepared in situ from the corresponding nucleosides and used for the next step without isolation. The procedure is simple and applicable to the preparation of various diphosphates of ribo- and deoxyribonucleosides, and their analogues.

Graphical Abstract

Keywords:

• Nucleotide analogues
• NDPs synthesis
• nucleoside 5′-diphosphates
• nucleoside 5′-H-phosphonates

Acknowledgments

We are grateful to Prof. Jacek Stawinski for valuable discussions and careful reading of this manuscript.

Additional information

Funding

Financial support from the National Centre for Research and Development [Grant LIDER/041/711/L-4/12/NCBR-2013 to J.R.] is gratefully acknowledged.