SPPS coupling reagents

The first version of SPPS to be developed used the t-Boc group as the amino-protecting group. f-Boc can be cleaved with relatively mild acidic treatment and TFA is usually used. The original coupling reagents utilized for SPPS were carbodiimides. In addition to dicyclohexylcarbodiimide (DCCI), N, (V -diisopropylcarbodiimide (DIPCDI) is often used. The mechanism of peptide coupling by carbodiimides was... 

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. 

Solid phase peptide synthesis[6, 7] (SPPS) is now an established methodology for the synthesis of small- to medium-sized peptides. Since the first reports on this technique in the early 1960s [3] several improvements in protecting groups, coupling reagents and solid supports have allowed access to a broad range of peptides in a routine and automatic manner. However, the synthesis of complex peptides... 

Carbodiimides were the coupling reagents most commonly used in solid-phase synthesis (SPS) until about 1985 (Fig. 3) [13-15]. For conducting SPS involving an intermediate treatment with trifluoroacetic acid (TFA) [e.g., solid-phase peptide synthesis (SPPS) by the rert-butoxycarbonyl (Boc)/... 

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). 

Solid-phase peptide synthesis (SPPS) (Section 24.7D) A method of peptide synthesis in which the peptide is synthesized on a solid support, one amino acid residue at a time. The first amino acid of the peptide is bonded as an ester between its carboxylic acid group and a hydroxyl of the solid support (a polymer bead). This is then treated with a solution of the second amino acid and appropriate coupling reagents, creating a dipeptide. Excess reagents, byproducts, etc. are washed away. Further linkages are synthesized in the same manner. The last step of the synthesis is cleavage of the p>eptide from the solid support and purification. 

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