Aromatic amino acid ethyl esters

Finally, as an old example of kinetic resolution of racemic mixtures, mention must be made on the report of Kise and Tomiuchi on the significant effect of acetonitrile on the enantioselectivity of different proteases toward the kinetic resolution of aromatic amino acid ethyl esters (5-8). For instance, (l)-DOPA (8) was obtained with 99% ee in the presence of 90% v/v acetonitrile [9]. 

Pish protein concentrate and soy protein concentrate have been used to prepare a low phenylalanine, high tyrosine peptide for use with phenylketonuria patients (150). The process includes pepsin hydrolysis at pH 1.5 ptonase hydrolysis at pH 6.5 to Hberate aromatic amino acids gel filtration on Sephadex G-15 to remove aromatic amino acids incubation with papain and ethyl esters of L-tyrosine and L-tryptophan, ie, plastein synthesis and ultrafiltration (qv). The plastein has a bland taste and odor and does not contain free amino acids. Yields of 69.3 and 60.9% from PPG and soy protein concentrate, respectively, have been attained. 

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. 

It is not possible to prepare biaryls containing a free carboxyl group directly by the diazo reaction. No biaryl is formed when (a) diazotized aniline and sodium benzoate, (b) diazotized anthranilic acid and aqueous sodium benzoate, or (c) diazotized anthranilic acid and benzene are used as components in the reaction.13 On the other hand, the reaction proceeds normally if methyl benzoate is used in reaction (a) or when methyl anthranilate replaces the anthranilic acid in (b) and in (c). The success of the diazohydroxide reaction appears to lie in the ability of the non-aqueous liquid to extract the reactive diazo compound from the aqueous layer.4 However, esters and nitriles can be prepared from esters of aromatic amino acids and cyanoanilines and also by coupling with esters of aromatic acids, and from the products the acids can be obtained by hydrolysis. By coupling N-nitrosoacetanilide with ethyl phthalate, ethyl 4-phenylphthalate (VIII) is formed in 37% yield. 

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. 

The specificity of chymotrypsin for hydrolysis of peptide bonds formed by the carbo,xyl groups of tyrosine, phenylalanine, and tryptophan has been recognized for some time (Green and Neurath, 1954 Desnuelle, 1960). Action on synthetic substrates of leucine (Goldenberg et al., 1951) and methionine (Kaufman and Neurath, 1949) also has been noted although at much slower rates than observed with the aromatic amino acid derivatives. When protein substrates or synthetic ester substrates are examined, it is evident that a variety of bonds can be hydrolyzed by chymotrypsin. Inagami and Sturtevant (1960) observed that chymotryptic hydrolysis of a-benzoyl-L-arginine ethyl ester, a typical trypsin substrate, occurred at a maximum rate which was 20% of that observed with trypsin. Several ester substrates, such as p-nitrophenylacetate (Hartley and Kilby, 1954), are also hydrolyzed. 

Enzymes other than CAL B have also been reported to operate under the biphasic conditions. CAL A and CAL B or a lipase from Mucor miehei were tested for the kinetic resolution of glycidol using vinyl acetate or vinyl butyrate. The enzymes were used either suspended in the free ILs or immobilized, when the reactions were carried out in [EMIM][NTf2] [71]. CALAwas inactive, butthe other two enzymes showed activity, albeit at 10-20% of that in the absence of COj whether they were free or immobilized. In general, the supported enzymes showed superior performance [71]. Chymotripsin, a specific protease for aromatic amino acids, was found to catalyze the hydrolysis or transesterification of the ethyl ester of N-acetyl-phenylalanine with propanol in scC02-[RMIM][PF5] (R = butyl or octyl) with or without added water [Eq. (15)]. 

CAS 65816-20-8 EINECS/ELINCS 265-932-4 Synonyms Benzoic acid, 4-(((ethylphenylamlno) methylene) amino)-, ethyl ester Ethyl 4-[[(ethylphenylamlno) methylene] amino] benzoate 4-[(Ethylphenylamlno) methyleneamino] benzoic acid ethyl ester Classification Aromatic amide Empirical CisHzoNjOj... 

An important question in molecular imprinting has been addressed using covalent binding by two boronic acids to what extent can imprinted polymers also bind substances other than the template. For example, are racemates of other substances resolvable In the first experiments on glyceric acid esters 5 with a certain ester as template, imprinted polymers were shown to resolve a whole series of racemates even when the alcohol group in the racemate is varied (methyl, ethyl, benzyl, or 4-nitrophenyl) [39]. Aromatic amino acids were shown to behave similarly. Here, the aromatic group in the racemates can vary. A racemate resolution is possible provided that the rest of the structure remains the same [40]. 

The diazotization of heteroaromatic amines is basically analogous to that of aromatic amines. Among the five-membered systems the amino-azoles (pyrroles, diazoles, triazoles, tetrazoles, oxazoles, isooxazoles, thia-, selena-, and dithiazoles) have all been diazotized. In general, diazotization in dilute mineral acid is possible, but diazotization in concentrated sulfuric acid (nitrosylsulfuric acid, see Sec. 2.2) or in organic solvents using an ester of nitrous acid (ethyl or isopentyl nitrite) is often preferable. Amino derivatives of aromatic heterocycles without ring nitrogen (furan and thiophene) can also be diazotized. 

Completion of the total synthesis afforded only six further steps, including the installation of the second 2-aminopyrimidine ring via a second domino sequence. This process presumably involves a conjugate addition of guanidine (2-293) to the enone system of2-292, followed by a cyclizing condensation and subsequent aromatization. Under the basic conditions, the ethyl ester moiety is also cleaved and 2-294 is isolated in form of the free acid, in 89 % yield. Finally, decarboxylation and deprotection of the amino functionality yielded the desired natural product 2-295. 

Parmar et al have developed a method for resolving racemic mixtures of a variety of natural and nonnatural amino acids using the ethyl ester of the amino acid protected at the amino position hy the formation of a Schiff base with an aromatic aldehyde such as /)-chlorobenzaldehyde. Both chymotrypsin and Lip such as porcine Lip gave good yields of the L-amino acid which precipitates out of solution as the amino acid ester released from the imine is cleaved by the hydrolase. 

Supported catalysts were used for the hydrogenation of the aromatic ring of 4-amino-benzoicacid and its ethyl ester, whereas Raney nickel was applied to catalyze the cis trans isomerization of 4-amino-cyclohexane carboxylic acid. 

Keywords aromatic aldehyde, primary amine, malonic acid monoethyl ester, Rodionov reaction, microwave irradiation, / -aryl-/ -amino acid ester, ethyl cinna-mate... 

Melphalan and the racemic analog have been prepared by two general routes (Scheme I). In Approach (A) the amino acid function is protected, and the nitrogen mustard moiety is prepared by conventional methods from aromatic nitro-derivatives. Thus, the ethyl ester of N-phthaloyl-phenylalanine was nitrated and reduced catalytically to amine I. Compound I was reacted with ethylene oxide to form the corresponding bis(2-hydroxyethyl)amino derivative II, which was then treated with phosphorus oxychloride or thionyl chloride. The blocking groups were removed by acidic hydrolysis. Melphalan was precipitated by addition of sodium acetate and was recrystallized from methanol. No racemization was detected [10,28—30]. The hydrochloride was obtained in pure form from the final hydrolysis mixture by partial neutralization to pH 0.5 [31]. Variants of this approach, used for the preparation of the racemic compound, followed the same route via the a-acylamino-a-p-aminobenzyl malonic ester III [10,28—30,32,33] or the hydantoin IV [12]. 

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