Activation
Carboxylic acids react with
amines at room temperature to give an ammonium
salt instead of a carboxamide. For formation of
the peptide bond to occur, activation of the carboxyl
group of the N-a-protected amino acid must occur.
Activation decreases the electron density of the
C=O group by introduction of an electron-accepting
species. This permits nucleophilic attack of the
amino component that results in peptide bond formation.
Several main activation strategies
commonly used for coupling reactions exist.
Phosphonium
+ Uronium
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