Base protecting group with acyl function

The sulfhydryl functional group of Cys is an excellent nucleophile and is easily acylated or alkylated hence it must be protected during SPPS. Oxidation to form the disulfide may also occur if Cys is left unprotected. Many of the suggested protecting groups are compatible with both Boc and Fmoc SPPS as they are not base or acid labile. 

Merrifield s original idea was based on the general scheme of stepwise condensation of N-protected amino acids to the first one, which is linked with its carboxyl function by an ester bond to the insoluble polymer support. This way of solid phase peptide synthesis resulted from the well-known risk of racemization during activation of peptidic carboxyl components, which is minimized in activated amino acid derivatives, N-acylated by urethane-type protecting groups [40] (Fig. 7). Depending on the chosen method, the C-terminal activation of N-protected peptides tends to racemize a certain amount of the material because of the possible formation of an oxazolinone intermediate [41] (Fig. 8). 

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