Leypold_2015_Tetrahedron.Lett_56_5619

Abstract: Fluorophosphonates represent powerful probes for the identification and analysis of active serine hydrolases in activity based protein profiling. Although alkylphosphonofluoridates are widely used for such purposes, little is known about the synthesis and purification of arylphosphonofluoridates, which may be useful tools for screening enzyme activities toward aromatic esters. Our optimized route makes this subclass of transition state inhibitors broadly accessible for a diverse series of phosphonic acid derivatives using a combination of selective monoesterification with EDC.HCl and subsequent mild fluorination with DAST. All compounds were isolated as pure materials using a simple acid-base extraction protocol in 7693% yields over two steps. These probes can be stored under an inert atmosphere at -24C for several months without significant degradation.