Aminolysis amino acids

Peptides can be formed by aminolysis of iV-aminoacyl-3,5-dimethylpyrazole with free amino acid esters 303 as shown in Table 5-5. 

It is truly amazing under what conditions, using completely different methods, amino acids can be linked up with elimination of water. Thus, it has been known for years that micelles (see Sect. 10.2) can catalyse various types of reactions in aqueous media, e.g., hydrolysis or aminolysis. Micelles are aggregates which form in aqueous solution from tensides under certain conditions (temperature, concentration). Cetyltrimethylammonium bromide (Cl llr J micelles (this... 

NL Benoiton, Y Lee, FMF Chen. Racemization during aminolysis of mixed and symmetrical anhydrides of IV-alkoxycarbonylamino acids by amino acid anions in aqueous dimethylformamide. Int J Pept Prot Res 31, 443, 1988. 

The reagents and methods employed for coupling in solid-phase synthesis are the same as for synthesis in solution, but a few are excluded because they are unsuitable. The mixed-anhydride method (see Section 2.6) and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline (see Section 2.15) are not used because there is no way to eliminate aminolysis at the wrong carbonyl of the anhydride. Acyl azides (see Section 2.13) are too laborious to make and too slow to react. The preparation of acyl chlorides (see Section 2.14) is too complicated for their routine use this may be rectified, however, by the availability of triphosgene (see Section 7.13). That leaves the following choices, bearing in mind that a two to three times molar excess of protected amino acid is always employed. 

J Pless, RA Boissonnas. On the velocity of aminolysis of a variety of new activated N-protected a-amino-acid phenyl esters, in particular 2,4,5-trichlorophenyl esters. Helv Chim Acta 46, 1609, 1963. 

Peptide bond formation involves activation of the carboxyl group of an amino acid residue, followed by aminolysis of the activated residue by the amino group of a second amino acid residue. Two types of activated molecules are recognized those that are not detectable but are postulated and those that are detectable and can be isolated. Postulated intermediates are necessary to account for the formation of the detectable intermediates. The postulated intermediates are consumed as fast as they are formed, either by aminolysis by an amino group or by nucleophilic attack by an oxygen nucleophile, which produces activated molecules that are also immediate precursors of the peptide. More than one activated compound may be generated by a postulated intermediate. Activated esters, acyl halides and azides, and mixed and symmetrical anhydrides are isolatable activated compounds that are generated from postulated intermediates. Peptides are produced by one of three ways ... 

AMINOLYSIS OF SUCCINIMIDO ESTERS BY UNPROTECTED AMINO ACIDS OR PEPTIDES... 

FIGURE 7.31 Aminolysis of a succinimido ester by (A) an amino-acid anion generated by base [Anderson et al., 1974] and (B) a peptide anion that is in equilibrium with the peptide.114 Pg = protecting group. Appropriate solvents are tetrahydrofuran, acetone, or dimethylforma-mide with water. 

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