A robust and simple protocol for the synthesis of arylfluorophosphonates. Issue 41 (7th October 2015)

• Record Type: Journal Article
• Authors: Leypold, Mario; Wallace, Paal W.; Kljajic, Marko; Schittmayer, Matthias; Pletz, Jakob; Illaszewicz-Trattner, Carina; Guebitz, Georg M.; Birner-Gruenberger, Ruth; Breinbauer, Rolf
• Is Part Of: Tetrahedron letters. Volume 56:Issue 41(2015)
• Page Start: 5619
• Page End: 5622
• Publication Date: 2015-10-07
• Subjects: Arylphosphonofluoridates -- Activity based probes -- Monoesterification -- DAST fluorination -- Pyrophosphonates; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2015.08.061
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: 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 76–93% yields over two steps. These probes can be stored under an inert atmosphere at −24 °C for several months without significant degradation.