3     Carboxyl Protecting Groups.

Protection of the carboxyl group is required for three main reasons:

 

1.   To enhance the solubility of the peptide in organic solvents.

2.   To avoid anhydride formation in the presence of activated amino acids.

3.   To allow unambiguous activation in the presence of a coupling reagent (only the unprotected carboxyl group can be activated).

 

Most of the commonly used groups are based on alkyl esters, with methyl and ethyl esters providing the most straightforward examples. Deprotection of these is achieved by treatment with sodium hydroxide in alcoholic solvent. Use of benzyl or substituted benzyl esters allows for deprotection with strong acid (HBr/acetic acid) or by catalytic hydrogenolysis. Tcrt butyl esters are used where milder acidic deprotection is required; treatment with trifluoroacetic acid or solution of HCI in organic solvents being required. In practice most commonly used carboxyl protecting groups have been applied, even the highly labile trimethyl silyl esters.

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