Ball‐Milling to Access Dinucleoside Polyphosphates and Analogues

Abstract

AbstractDinucleoside 5’,5’‐polyphosphates (NpnNs) play essential roles in various biological processes. Access to these high value‐added compounds, while avoiding the many drawbacks of solution phase synthesis, is a challenge that has been overcome thanks to mechanochemistry. A straightforward solid‐state synthesis based on activation of phosphate or pyrophosphate sodium salts to their diimidazolides, followed by coupling with commercially available nucleotides, under air conditions, gave symmetrical NpnNs. The scope ranged from Np3Ns to highly challenging Np6Ns. The methodology has also been implemented using medronic acid and imidodiphosphate to obtain NpnNs analogues, some of which are unprecedented.