Protectors Sensitized or Stabilized to Acidolysis

FIGURE 3.23 Protectors that are more sensitive or more stable to acidolysis than the parent protector. Electron-donating groups favor protonation and hence aid cleavage electron-withdrawing groups disfavor protonation. The numbers indicate the relative ease of cleavage, which also depends on the stability of the carbenium ion that is released. Bpoc = 2-(biphenyl-4-yl)-prop-2-yloxycarbonyl. 

FIGURE 3.25 The triphenylmethyl group for protection63-64 of side-chain and carboxy-ter-minal functional groups. The triphenylmethyl-heteroatom bond is sensitive to mild acid. 

The notion of stabilized and sensitized protectors is pertinent to solid-phase synthesis in particular. Practically all of the linkers through which carboxy-terminal residues are attached to the solid support are composed of benzyl that has been substituted with functional groups such as dialkoxy, dimethoxyphenyl, phenyl (ben-zhydryl), diphenyl (trityl), chlorodiphenyl (chlorotrityl, see Section 5.23), or other to modify the stability of the linking bond.9-63-73 

R Schwyzer, W Rittel, H Kappeler, B Iselin. Synthesis of a nonadecapeptide with higher corticotropic activity, (ferf-butyl removal) Angew Chem 72, 915, 1960. 

G Amiard, R Heymes, L Velluz. On IV-trityl-a-amino acids and their application in peptide synthesis. Bull Soc Chim Fr 191, 1955. 

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