An overview of solvent-free and solvent/s-involved phosphorylation to synthesize Zoledronic acid

Abstract

This work provides a complete overview of solvent-free and solvent-involved phosphorylation strategies employed to synthesize the renowned biphosphonate drug, Zoledronic acid. In this regard, all the disclosed patents and journal publications were considered and reviewed as per the yearly chronology towards the use of solvent/s or in the absence of it for the phosphorylation. Interestingly, a prolonged reaction time, sticky lump formation, exothermicity, enormous HCl release, tedious workup, etc had allowed the researchers to venture various synthetic and isolation approaches to overcome the process-specific setbacks. In line to this context, various solvent/s were used alone or in combination with another solvent to synthesize Zoledronic acid in varied yields. A few attempts were also reported under solvent-free conditions in reasonably good yields. Moreover, along with the above variations, a few different p-reagent/s are also reported towards the synthesis of Zoledronic acid.