An effective method for bisphosphonate moiety inserting into O–H bond of carboxylic acids by Cu (II) catalyst

Abstract

In this study we developed a novel copper-catalyzed O–H insertion of tetraethyl diphosphonodiazomethane into carboxylic acids, providing a simple method to link bisphosphonates to compounds containing carboxyl group. Moreover, a novel bone-targeting prodrug of naproxen was synthesized according to this new methodology, and the preliminary evaluation indicated that the prodrug exhibited excellent bone affinity in vitro.