Reactions of the Amino and Carboxy Groups

Only a few esters of dehydroamino acids are stable and these only as hydrochlorides, so that all the reactions at the amino group studied to date are electrophilic. As the enamino group is less nucleophilic than an amino group, enamino acid esters can only be acylated by the most reactive acid derivatives, such as acid chlorides (368, 373) and mixed anhydrides (69, 257, 313). Attempted peptide formation from acylamino acids and enamino acid esters by the DCCD or DCCD/hydroxysuccini-mide methods is unsuccessful. The formation of Schiff bases at the enamino group proceeds rather slowly, but can be achieved in the case of the stable dehydrovaline methyl ester by direct condensation with aromatic aldehydes (287, 352). 

Peptide formation by acylation of amino acid esters with N-acyl-dehydroamino acids can be carried out by employing activated derivatives of the latter. Suitable derivatives are the N-carboxy-a-amino acid anhydrides (226), or mixed anhydrides (257, 314). Coupling with DCCD/ N-hydroxysuccinimide is also applicable (314B). 

For the construction of peptides with an N-methyldehydroamino acid unit, use can be made of the observation by Rich (328) that selective N-methylation of N-acyl enamino acid units can be carried out with methyl iodide/potassium carbonate in dimethylformamide. 

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Part 1 of this chapter is intended to provide background material for the analytical procedures described later in this chapter for amino acids and peptides, but it also provides a broad survey of the topic that can be read in isolation from the analytical context. The derivatisation of amino acids is the basis of many of the sensitive analytical amino-acid assay procedures in current use and this chapter covers the normal profile of reactions of the amino and carboxy groups, knowledge of which is an essential prerequisite for appreciating the analytical context. Reactions of peptides are also covered here (e.g. peptide and protein hydrolysis is covered in Section 4.4.7), though the coverage is restricted in scope because parts of this topic are discussed in Chapter 5, where it is relevant to sequence-determination procedures (see also Barrett, 1985). 

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