Solid-Phase Synthesis as Developed by Merrifield

The next residues were attached successively by dicyclohexylcarbodiimide-mediated coupling of Boc-amino acids with the free amino groups. The use of excess Boc-amino acid eliminated the need for capping after coupling. The last Boc-group and the benzyl-based side chain and carboxy-terminal protectors were removed at the end of the synthesis by acidolysis with hydrogen bromide in trifluoroacetic acid the latter was used instead of acetic acid to avoid acetylation of hydroxymethyl side chains (see Section 6.6). Catalytic hydrogenolysis of the peptide removed the nitro 

FIGURE 5.2 Synthesis of a peptide on a solid support according to Merrifield in 1964. PS = polystyrene. Initially, the protector was benzyloxycarbonyl, removed by HBr in CHjCOjH, followed by final deprotection with the same reagent at 78°C. The current protocol employs CF3C02H and HF, respectively. 

RB Merrifield. Solid phase synthesis. I. The synthesis of a tetrapeptide. J Am Chem Soc 85, 2149, 1963. 

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