7 Phenylpyruvic acid

Some people lack the enzymes necessary to convert L phenylalanine to L tyrosine Any L phenylalanine that they obtain from their diet is diverted along a different meta bolic pathway giving phenylpyruvic acid... 

Phenylpyruvic acid can cause mental retardation m infants who are deficient m the enzymes necessary to convert l phenylalanine to l tyrosine This disorder is called phenylketonuria, or PKU disease PKU disease can be detected by a simple test rou tmely administered to newborns It cannot be cured but is controlled by restricting the dietary intake of l phenylalanine In practice this means avoiding foods such as meat that are rich m l phenylalanine... 

Cm.OROCARBONSANDCm.OROHYDROCARBONS - BENZYL Cm ORIDE, BENZAL Cm ORIDE AND BENZOTRICm ORIDE] (Vol 6) Phenylpyruvic acid [156-06-9]... 

Substitution in position 4 displays a more complex influence. Cyclization of the 4-methyl- and 4-ethyl-thiosemicarbazones of phenylpyruvic acid and of the 4-methylthiosemicarbazone of phenyl-glyoxylic acid (103) was readily achieved (104), whereas it was not possible to cyclize the analogous 4-methyl derivatives of pyruvic and glyoxylic acids. It thus appears that cyclization is hindered by substitution in position 4 and that this unfavorable effect can be partly relieved by the known favorable effect of an aryl or aralkyl group in the a-position. 

Figure 8.7 Fed-batch fermentation of phenylpyruvic acid to L-phenylalanine.

A possible explanation for the superiority of the amino donor, L-aspartic add, has come from studies carried out on mutants of E. coli, in which only one of the three transaminases that are found in E. coli are present. It is believed that a branched chain transaminase, an aromatic amino add transaminase and an aspartate phenylalanine aspartase can be present in E. coli. The reaction of each of these mutants with different amino donors gave results which indicated that branched chain transminase and aromatic amino add transminase containing mutants were not able to proceed to high levels of conversion of phenylpyruvic add to L-phenylalanine. However, aspartate phenylalanine transaminase containing mutants were able to yield 98% conversion on 100 mmol l 1 phenylpyruvic acid. The explanation for this is probably that both branched chain transaminase and aromatic amino acid transminase are feedback inhibited by L-phenylalanine, whereas aspartate phenylalanine transaminase is not inhibited by L-phenylalanine. In addition, since oxaloacetate, which is produced when aspartic add is used as the amino donor, is readily converted to pyruvic add, no feedback inhibition involving oxaloacetate occurs. The reason for low conversion yield of some E. coli strains might be that these E. cdi strains are defident in the aspartate phenylalanine transaminase. 

The liquid is transferred to a continuous extractor (Note 10) and extracted with ether until the supernatant layer of ether remains colorless (about 2 hours). The ethereal extract is discarded (Note 11). The aqueous solution is transferred to a 1-1. beaker and acidified by the cautious addition of 60 ml. of 121V hydrochloric acid (Note 12). The solution is returned to the extractor, which is attached to a tared round-bottomed flask. The solution is extracted with ether until no more -hydroxyphenylpyruvic acid is obtained (Note 13). The undried ether solution is evaporated to dryness on a boiling water bath to give crude p-hydroxy-phenylpyruvic acid as a pale-yellow crystalline mass. The mass is broken up with a spatula, and the flask is kept over potassium hydroxide in a vacuum desiccator until its weight is constant. The yield of crude acid is 6.9-7.2 g. (92-96%). It melts at 210— 215° (dec.) (Note 14). 

Finally, this method is of general utility, for alkaline cleavage of analogously substituted hydantoins has given a series of substituted phenylpyruvic acids.12... 

Phenylpyruvic acids by hydrolysis of phenylhydantoins, 43, 49 1-Phenyl-2-THiOBiuRET, 42, 87 l-Phenyl-2-thio-4-ethylisobiuret, 42, 89 l-Phenyl-2-thio-4-methylisobiuret, 42, 87... 

Alternatively to the Japp-Klingemann reaction phenylpyruvic acid or ethyl phenylpyruvatc can be condensed with 4-chlorophenylhydrazine.J... 

Denoya CD, DD Skinner, MR Morgenstern (1994) A Streptomyces avermitilis gene encoding a 4-hydroxy-phenylpyruvic acid dioxygenase-like protein that directs the production of homogentisic acid and an ochronotic pigment in Escherichia coli. J Bacterial 176 5312-5319. 

R. Fernandez-Lafuente, V. Rodriguez, and J.M. Guisan, The coimmobilization of D-amino acid oxidase and catalase enables the quantitative transformation of D-amino acids (D-phenylalanine) into alpha-keto acids (phenylpyruvic acid). Enz. Microb. Technol. 23, 28-33 (1998). 

To 23 g Na in 350 ml ethanol add 146 g ethyl-oxalate and 171 g 2-nitro-6-CI-toluene and reflux forty minutes. Dilute the red solution with water and steam distill until no more starting material is distilled. The aqueous residue is filtered, acidified with HC1 and filtered to get 102 g 2-nitro-6-CI-phenylpyruvic acid (I) (recrystallize-benzene). Add 81 g (I) in dilute NH4OH to a solution of 560 g FeS04.7H20 and 230 ml concentrated NH4OH and 2 L water and boil five minutes. Filter, wash precipitate with dilute NH4OH, water and acidify filtrate with dilute HCI to get 60 g 4-CI-2-indole-COOH (11) (recrystallize-aqueous ethanol). 9.78 g (II) and 6.7 g CuCN in 35 g quinoline and reflux (about 237°) for twenty hours. Pour the hot solution into a mixture of 25 ml concentrated HCI and ice. Stir and filter wash precipitate with water and extract the filtrate and precipitate three times with ether. Wash the ether with HCI, water and dry, evaporate in vacuum to get 3.6 g 4-CN-indole (recrystallize-water). Or, heat (II) alone at 290° until fusion then heat at 250° for ten minutes until C02 evolution ceases to get 4-CN-indole. For conversion to 4-formyl-indole see HC A 51,1616(1968). 

Intermediate diketopiperazine derivatives have been employed in the diastereoselective synthesis of benzyltetra-hydroisoquinoline by 1,4-chirality transfer. iV-Cbz-Proline was coupled with 2-(3,4-dimethoxyphenyl)ethylamine and the resulting amide 109, after deprotection, was reacted with phenylpyruvic acid (Cbz = carbobenzyloxy group). Compound 110 underwent acid-catalyzed Pictet-Spengler condensation to yield final tetracyclic... 

L-Amino acid oxidase has been used to measure L-phenylalanine and involves the addition of a sodium arsenate-borate buffer, which promotes the conversion of the oxidation product, phenylpyruvic acid, to its enol form, which then forms a borate complex having an absorption maximum at 308 nm. Tyrosine and tryptophan react similarly but their enol-borate complexes have different absorption maxima at 330 and 350 nm respectively. Thus by taking absorbance readings at these wavelengths the specificity of the assay is improved. The assay for L-alanine may also be made almost completely specific by converting the L-pyruvate formed in the oxidation reaction to L-lactate by the addition of lactate dehydrogenase (EC 1.1.1.27) and monitoring the oxidation of NADH at 340 nm. 

Not unexpectedly, alkylation of the double carbonylated complex proceeds via a base-catalysed interfacial enolization step, but it is significant that the initial double carbonylation step also involves an interfacial reaction, as it has been shown that no pyruvic acid derivatives are obtained at low stirring rates. Further evidence comes from observations of the cobalt-catalysed carbonylation of secondary benzyl halides [8], where the overall reaction is more complex than that indicated by Scheme 8.3. In addition to the expected formation of the phenylacetic and phenylpyruvic acids, the reaction with 1-bromo-l-phenylethane also produces 3-phenylpropionic acid, 2,3-diphenylbutane, ethylbenzene and styrene (Scheme 8.4). The absence of secondary carbonylation of the phenylpropionylcobalt tetracarbonyl complex is consistent with the less favourable enolization of the phenylpropionyl group, compared with the phenylacetyl group. 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

Biological. Reported biodegradation products include 2,3-dihydro-2,3-dihydroxybiphenyl, 2,3-dihydroxybiphenyl, 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate, 2-hydroxy-3-phenyl-6-oxohexa-2,4-dienoate, 2-oxopenta-4-enoate, phenylpyruvic acid (quoted, Verschueren, 1983), 2-hydroxy-biphenyl, 4-hydroxybiphenyl, and 4,4 -dihydroxybiphenyl (Smith and Rosazza, 1974). The microbe Candida lipolytica degraded biphenyl into the following products 2-, 3-, and 4-hydroxy-biphenyl, 4,4 -dihydroxybiphenyl, and 3-methoxy-4-hydroxybiphenyl (Cerniglia and Crow, 1981). 

Phenylpentane, see Propylbenzene Phenylphenol, see 2-Chlorobiphenvl 2-Phenylpropionaldehyde, see Isopropylbenzene Phenylpyruvic acid, see Biphenyl l-Phenyl-3-(l,2,5-thiadiazol-3-yl)urea, see... 

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