Reactions of Amino Acids

FIGURE 22.26 Reactions of the carboxylate group of amino acids. 

FIGURE 22.27 Amino add reduction in the synthesis of S-ferf-BuPHOX. This is a chiral ligand used in a number of enantioselective metal catalysed processes. 

One reaction unique to amino acids is that with ninhydrin, 22.29. Ninhydrin itself is colorless, but the product is an intense blue-purple in color (proline gives a yellow-orange product). The color is exceptionally intense, so that the amounts of amino acids can be determined quantitatively, even if only micrograms are present. Recent applications have included the use of ninhydrin to visualize fingerprints human sweat contains small amounts of amino acids released from the termini of peptides. 

Propose a reaction mechanism for the reaction of ninhydrin with amino acids. PROBLEM 22.9 

Predict the product(s) of each of the following reaction sequences  

In addition to their acidic and basic behavior, amino acids undergo other reactions typical of carboxylic acids or amines. For example, the carboxyl group can be esterified  

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Direct Amidation. The direct reaction of amino acids to form Type AB polyamides (eq. 1) and diacids and diamines to form type AABB polyamides (eq. 2) ate two of the most commonly used methods to produce polyamides. The... 

X-Amino acids ate ampholytic compounds. The chemical reactions of amino acids can be classified according to their carboxyl, amino, and side-chain groups. Most of the reactions have been well known for a long time the details of these reactions have been reviewed (77). 

In these cases, it is better to protect the carboxyl group. Optimized conditions for A/-acetylation have been studied (78). A/-Acylation can be utilized for protecting the amino group in the reaction of amino acids, for example in peptide synthesis. 

Reaction with Phosgene. This reaction of amino acid esters is used for preparing the corresponding isocyanates, especially lysine diisocyanate [4460-02-0] (LDI). LDI is a valuable nonyellowing isocyanate with a functional side group for incorporation in polyurethanes. 

Formation of N-Carboxy-(X-Amino AeidAnhydride (NCA) (85), NCAs are important as starting materials for amino acid polymers. They are prepared by the reaction of amino acids with phosgene in an aptotic solvent. 

A key biochemical reaction of amino acids is their conversion to peptides, polypeptides, and proteins. In all these substances fflnino acids aie linked together by amide bonds. The amide bond between the fflnino group of one amino acid and the caiboxyl of another is called a peptide bond. Alanylglycine is a representative dipeptide. 

Specific Reactions of Amino Acid Side Chains... 

A number of reactions of amino acids have become important in recent years because they are essential to the degradation, sequencing, and chemical synthesis of peptides and proteins. These reactions are discussed in Chapter 5. 

FIGURE4.il Reactions of amino acid side-chain functional groups. 

Nylon resins are important engineering thermoplastics. Nylons are produced by a condensation reaction of amino acids, a diacid and a diammine, or by ring opening lactams such as caprolactam. The polymers, however, are more important for producing synthetic fibers (discussed later in this chapter). 

Solid-phase Diels-Alder reactions of amino acid derived trienes [23]... 

Tible 1 Color reactions of amino acids with fluorescein isothiocyanate — ninhydrin (extract from original table). 

FUNCTIONAL GROUPS DICTATE THE CHEMICAL REACTIONS OF AMINO ACIDS... 

Each functional group of an amino acid exhibits all of its characteristic chemical reactions. For carboxylic acid groups, these reactions include the formation of esters, amides, and acid anhydrides for amino groups, acylation, amidation, and esterification and for —OH and —SH groups, oxidation and esterification. The most important reaction of amino acids is the formation of a peptide bond (shaded blue). 

Of the biochemical reactions of amino acids, the most important is the formation of peptide bonds. 

Removal of a-amino nitrogen by transamination (see Figure 28-3) is the first catabolic reaction of amino acids except in the case of proline, hydroxyproline, threonine, and lysine. The residual hydrocarbon skeleton is then degraded to amphibolic intermediates as outhned in Figure 30-1. 

Transamination is the most common initial reaction of amino acid catabohsm. Subsequent reactions remove any additional nitrogen and restmcmre the hydrocarbon skeleton for conversion to oxaloacetate, a-ketoglutarate, pyruvate, and acetyl-CoA. 

As the name implies, an amino acid is a bifunctional molecule with a carboxylic acid group at one end and an amine group at the other. All proteins are polyamides made from condensation reactions of amino acids. Every amino acid in proteins has a central carbon atom bonded to one hydrogen atom and to a second group, symbolized in Figure 13-31 as R. 

Figure 4.4 Release of amino acids from cortical slices exposed to 50 mM K+. Measurements by HPEC and fluorescence detection after reaction of amino acids with o-phthalaldehyde 1, aspartate 2, glutamate 3, asparagine 4, serine 5, glutamine 6, histidine 7, homoserine (internal standard) 8, glycine 9, threonine 10, arginine 11, taurine 12, alanine 13, GABA 14, tyrosine. Glutamate concentration is almost 1 pmol/gl which represents a release rate of 30 pmol/min/mg tissue...

The reaction of amino acid imidazolides with the potassium salt of monomethyl malonate in the presence of one equivalent of MgCl2, CoCl2, or MnCl2 results in the formation of jS"keto-y-aminocarboxylates.[64]... 

Simulation experiments of a different type were carried out by two Japanese researchers (Matsunu, 2000 Imai et al., 1999a, b). They used a simulation reactor to study processes which may occur at hydrothermal vents (see Sect. 7.2). In this case, the activation energy for the polycondensation reaction of amino acids has its origin in the Earth s interior. In the high pressure hot water reactor used, the reaction... 

Amino Acid Dating Techniques depend on the "rates of hydrolysis reactions of proteins and racemization, epimerization, and decomposition reactions of amino acids [they have] been applied to the age-dating of fossil bone, teeth, and shell. Activation energies range from near 20 kcal per mole for hydrolysis reactions to around 30 kcal per mole for racemization... 

Young, D. W., Stereochemistry of Metabolic Reactions of Amino Acids, 21, 381. 

Figure 10.11 The ninhydrin reaction. The overall reaction of amino acids with ninhydrin is ...

The reaction of amino acids with HOCl was smdied using EPR spin trapping and UV-vis spectroscopy. Some nitrogen-centred radicals, which then undergo a variety of abstraction, rearrangement, and fragmentation reactions, were detected (Scheme 27). 

The same approach was recently used for the synthesis of a cyclopeptoid as potential inhibitor of the Tat/TAR complex of the HfV-1 virus (Scheme 24) [94, 95]. Two Ugi reactions were used to prepare fragment b that was coupled to fragment a to afford linear precursor c. The macrocyclic peptidomimetic d was obtained after cyclization employing Ugi reaction of amino acid c with paraformaldehyde and t-butyl isocyanide. 

Despite the uncertainties regarding regiochemistry, the reaction of propiolates with miinchnones has found use in synthesis. Kane and co-workers (84) synthesized the calcium channel activator FPL 64176 (161) using a mtinchnone cycloaddition protocol. Thus, reaction of amino acid 158 with acetic anhydride in the presence of acetylenic dipolarophUe 159 gave pyrrole 160 in 49% yield. Base-induced elimination of the 4-nitrophenethyl protecting group afforded FPL 64176 (161) in 85% yield. 

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