Synthesis of functionalized bisphosphonates via click chemistry

An efficient general synthetic approach giving the possibility for facile, rapid and cheap access to a wide range of novel nitrogen-bisphosphonates ( N-BPs) as potent drug candidates, based on the reaction of mono-and bis-propargyl-substituted bisphosphonates with a variety of azides under Cu(I) catalysis (click methodology), has been developed. The method allows the incorporation of two functionalities into the N-BP molecule simultaneously, as well as to ligate in situ two N-BPs to one another via the one-pot reaction of organic dibromides with propargyl-substituted bisphosphonates, generating both the diazide and Cu( I) moieties.