Straightforward Ball-Milling Access to Dinucleoside 5',5'-Polyphosphates via Phosphorimidazolide Intermediates

Lucie Appy; Anaïs Depaix; Xavier Bantreil; Frédéric Lamaty; Suzanne Peyrottes; Béatrice Roy

doi:10.1002/chem.201805924

Straightforward Ball-Milling Access to Dinucleoside 5',5'-Polyphosphates via Phosphorimidazolide Intermediates

Chemistry. 2019 Feb 18;25(10):2477-2481. doi: 10.1002/chem.201805924. Epub 2019 Jan 21.

Authors

Lucie Appy¹, Anaïs Depaix¹, Xavier Bantreil², Frédéric Lamaty², Suzanne Peyrottes¹, Béatrice Roy¹

Affiliations

¹ Nucleosides & Phosphorylated Effectors, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, ENSCM, Université de Montpellier, Campus Triolet, cc1705, Place Eugène Bataillon, 34095, Montpellier cedex 5, France.
² Green Chemistry and Enabling Technologies, Institut des Biomolécules Max Mousseron (IBMM), UMR 5247 CNRS, ENSCM, Université de Montpellier, Campus Triolet, cc1703, Place Eugène Bataillon, 34095, Montpellier cedex 5, France.

PMID: 30549335
DOI: 10.1002/chem.201805924

Abstract

A solvent-assisted mechanochemical approach to access symmetrical and mixed dinucleoside 5,5'-polyphosphates is reported. Under ball-milling conditions, nucleoside 5'-monophosphates were quantitatively activated using 1,1'-carbonyldiimidazole, forming their phosphorimidazolide derivatives. The addition of a nucleoside 5'-mono-, di- or triphosphate directly led to the formation of the corresponding dinucleotides. Benefits of the reported one-pot method include the use of unprotected nucleotides in their sodium or acid form, activation by the eco-friendly 1,1'-carbonyldiimidazole, non-dry conditions, short reaction time, high conversion rates, and easy setup and purification. This work offers new perspectives for the synthesis of nucleotide conjugates and analogues, combining the phosphorimidazolide approach and milling conditions.

Keywords: 1,1′-carbonyldiimidazole; green chemistry; mechanochemistry; nucleotides; pyrophosphate.