Aromatic amino compounds, acetylation

Acetylation. Most mammalian species are able to acetylate aromatic amino compounds, the major exception being the dog. Thus, for a number of amino compounds such as procainamide (chap. 4, Fig. 43), sulfadimethoxine, sulfamethomidine, sulfasomizole, and the N4 amino group of sulfanilamide (chap. 4, Fig. 68), the dog does not excrete the acetylated product. However, the dog does have a high level of deacetylase in the liver and also seems to have an acetyltransferase inhibitor in the liver and kidney. Consequently, acetylation may not be absent in the dog, but rather the products may be hydrolyzed or the reaction effectively inhibited. 

Acetylation. Most mammalian species are able to acetylate aromatic amino compounds, the major exception being the dog. Thus, for a number of amino compounds such as procainamide (figure 4,42),... 

In general, benzoylation of aromatic amines finds less application than acetylation in preparative work, but the process is often employed for the identification and characterisation of aromatic amines (and also of hydroxy compounds). Benzoyl chloride (Section IV, 185) is the reagent commonly used. This reagent is so slowly hydrolysed by water that benzoylation can be carried out in an aqueous medium. In the Schotten-Baumann method of benzoylation the amino compound or its salt is dissolved or suspended in a slight excess of 8-15 per cent, sodium hydroxide solution, a small excess (about 10-15 per cent, more than the theoretical quantity) of benzoyl chloride is then added and the mixture vigorously shaken in a stoppered vessel (or else the mixture is stirred mechanically). Benzoylation proceeds smoothly and the sparingly soluble benzoyl derivative usually separates as a solid. The sodium hydroxide hydrolyses the excess of benzoyl chloride, yielding sodium benzoate and sodium chloride, which remain in solution ... 

Figure 3-14 shows the spectra of N-acetyl ethyl esters of all three of the aromatic amino acids and of cystine. To a first approximation, the absorption spectra of proteins can be regarded as a summation of the spectra of the component amino acids. However, the absorption bands of some residues, particularly of tyrosine and tryptophan, are shifted to longer wavelengths than those of the reference compounds in water. This is presumably a result of being located within nonpolar regions of the protein. Notice that the spectra for tyrosine, phenylalanine, and cystine in Fig. 

The selective resolution enhancement in derivative spectroscopy is pushed even further in the fourth derivative mode. As in the case of second derivative spectroscopy, the amplitude and the position of the derivative spectral bands of the aromatic amino acids are related to the polarity of the medium. We have undertaken a systematic investigation of these spectral features of the N-acetyl O-ethyl esters of tyrosine and tryptophan in various solvents of different polarity (from cyclohexane to water). Astonishingly, a simple relationship between the spectral parameters of the fourth derivatives and the dielectric constant was found [11]. As shown in Figure 5, for tyrosine it is the position of >.max, and for tryptophan it is the derivative amplitude which depends linearly on the dielectric constant er. Since in addition the fourth derivative spectra of these model compounds do not depend significantly on pressure (at least up to 500 MPa), these spectral features may be used as an intrinsic probe to sense the dielectric constant in the vicinity of tyrosine and tryptophan. 

Seven amino acids produce acetyl CoA or acetoacetate and therefore are categorized as ketogenic. Of these, isoleucine, threonine, and the aromatic amino acids (phenylalanine, tyrosine, and tryptophan) are converted to compounds that produce both glucose and acetyl CoA or acetoacetate (Fig. 39.16). Leucine and lysine do not produce glucose they produce acetyl CoA and acetoacetate. 

Cardiovascular agents - The metabolites of metoclopramide, a compound re-lated to procaTnanide, were isolated from rabbit urine identified as mono-N-de-ethylated metoclopramide, 4-amino-5-chloro-2-methoxy benzoic acid, an unidentified metabolite that is an oxidation product of the aromatic amino group, and the sulfate and glucuronide conjugates of metoclopramide. Acetylation of the aromatic amino group apparently does not occur in the rabbit. 

Nitration. Direct nitration of aromatic amines with nitric acid is not a satisfactory method, because the amino group is susceptible to oxidation. The amino group can be protected by acetylation, and the acetylamino derivative is then used in the nitration step. Nitration of acetanilide in sulfuric acid yields the 4-nitro compound that is hydroly2ed to -rutroaruline [100-01-6]. 

Various hydroxyl and amino derivatives of aromatic compounds are oxidized by peroxidases in the presence of hydrogen peroxide, yielding neutral or cation free radicals. Thus the phenacetin metabolites p-phenetidine (4-ethoxyaniline) and acetaminophen (TV-acetyl-p-aminophenol) were oxidized by LPO or HRP into the 4-ethoxyaniline cation radical and neutral V-acetyl-4-aminophenoxyl radical, respectively [198,199]. In both cases free radicals were detected by using fast-flow ESR spectroscopy. Catechols, Dopa methyl ester (dihydrox-yphenylalanine methyl ester), and 6-hydroxy-Dopa (trihydroxyphenylalanine) were oxidized by LPO mainly to o-semiquinone free radicals [200]. Another catechol derivative adrenaline (epinephrine) was oxidized into adrenochrome in the reaction catalyzed by HRP [201], This reaction can proceed in the absence of hydrogen peroxide and accompanied by oxygen consumption. It was proposed that the oxidation of adrenaline was mediated by superoxide. HRP and LPO catalyzed the oxidation of Trolox C (an analog of a-tocopherol) into phenoxyl radical [202]. The formation of phenoxyl radicals was monitored by ESR spectroscopy, and the rate constants for the reaction of Compounds II with Trolox C were determined (Table 22.1). 

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