Protecting groups orthogonal stability

Trityl resins are particularly suitable for immobilization of nucleophilic substrates such as acids, alcohols, thiols, and amines. They are quite acid-sensitive and are cleavable even with acetic acid this is useful when acid-labile protecting groups are used. The stability of trityl resin can be tailored by use of substituted arene rings, as shown by chlorotrityl resin, which furnishes a more stable linker than the trityl resin itself. Steric hindrance also prohibits formation of diketopiperazines during the synthesis of peptides. Orthogonality toward allyl-based protective groups was demonstrated in the reverse solid-phase peptide synthesis of oligopeptides [30] (Scheme 6.1.4). 

In particular, the sensitive ferf-butyl ester as the C-terminal protection remained unaffected during both the mild activation procedure and the subsequent conversion of the Tcoc group into the acetamide (Scheme 17). With 32 in hand, the orthogonal stability of the terf-butyl and the Z protecting groups facilitates extension of the peptide chain in the N-terminal direction. 

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