Phosphonium SPPS coupling reagents

Coupling reagents based on phosphonium and uronium salts are now becoming more frequently used, both for the coupling of single annino acids in stepwise SPPS and for segment coupling in CSPPS. 

More recently, the use of phosphonium (e.g., benzotriazole-1-yl-oxy-tris-pyrrolidino phosphonium hexafluorophosphate (PyBOP)) and uronium (e.g., 2-(1H- benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU)) coupling reagents have gained wide use in effecting peptide bond formation, particularly in SPPS (Fig. 7.6). The structures of PyBOP and HBTU both incorporate an equivalent of HOBt, and the final reactive Boc or Fmoc amino acid species is the corresponding OBt active ester (13). 

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