Solid-phase peptide synthesis cleavage

H2/Pd-C, EtOH, 20°. < -Bromobenzyl carbonates have been developed for use in solid-phase peptide synthesis. An aryl o-bromobenzyl carbonate is stable to acidic cleavage (CF3CO2H) of a /-butyl carbamate a benzyl carbonate is cleaved. 

Mercaptopyridine A-oxide, CH2CI2. A thousand fold excess of this reagent is required to achieve good yields for cleavage in solid-phase peptide synthesis. 

This is traditionally justified since it removes the bulky fluorescent dye from the bioactive sequence. Nonacidic cleavage conditions in the release of targeted peptide from the resin is also a strategy when FTIC is used in solid phase peptide synthesis. 

DS King, CG Fields, GB Fields. A cleavage method which minimizes side reactions following Fmoc solid phase peptide synthesis. Ini J Pept Prot Res 36, 255, 1990. 

A thiazolium amino acid (Taz) has been developed which can be utilized to mimic TDP-dependent enzyme function [52]. In this strategy, illustrated in Fig. 15, the commercially available amino acid 4-thiazolylalanine is incorporated into peptides by solid phase peptide synthesis. Prior to deprotection of the amino acid side chains and cleavage of the peptide from the resin, the thiazole amino acid is alkylated with an alkyl halide to generate the corresponding thiazolium amino acid having various N3-substituents (BzTaz = 3-benzyl-Taz, NBTaz = 3-nitrobenzyl-Taz). 

Scheme 11 Synthesis of a Lanthionine Peptide via Solid-Phase Peptide Synthesis and Final Cleavage from Kaiser Oxime Resin 481...

Esters of the PAM linker are slightly more resistant towards acids than the corresponding 4-alkylbenzyl esters [5,25-27] (Table 3.1). The PAM linker is particularly well suited for solid-phase peptide synthesis using A-Boc amino acids because less than 0.02% cleavage of the peptide from the support occurs during the acidolytic deprotection steps [27], Esters of both the 4-alkylbenzyl alcohol and PAM linkers can also be cleaved by nucleophiles (see Sections 3.1.2 and 3.3.3). 

Numerous examples of different variants of this cyclization/cleavage protocol have been reported. Diketopiperazine formation (Section 15.22.1), an unwanted side reaction in solid-phase peptide synthesis, is also an example of this type of compound release. Because intramolecular processes generally take place more readily than the corresponding intermolecular reactions, cyclization/cleavage can occur with alkyl... 

Support-bound triacylmethanes (e.g. 2-acetyldimedone) readily react with primary aliphatic amines to yield enamines. These are stable towards weak acids and bases, and can be used as linkers for solid-phase peptide synthesis using either the Boc or Fmoc methodologies, as well as for the solid-phase synthesis of oligosaccharides [456]. Cleavage of these enamines can be achieved by treatment with primary amines or hydrazine (Entries 2 and 3, Table 3.23 see also Section 10.1.10.4). 

Figure 16.3. Solid-phase peptide synthesis using the Boc strategy [18,24]. All reactions, except the final cleavage, are performed at room temperature.

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