Phenyl pyruvic

This is a slow process, and the extraction time depends on the type of extractor used. With stirring as described in Note 10, practically quantitative extraction of jb-hydroxy phenyl pyruvic acid can be achieved within 6 hours. Extremely long extraction times may cause decomposition of the product. 

Recently, Borner and coworkers described an efficient Rh-deguphos catalyst for the reductive amination of a-keto acids with benzyl amine. E.e.-values up to 98% were obtained for the reaction of phenyl pyruvic acid and PhCH2COCOOH (entry 4.9), albeit with often incomplete conversion and low TOFs. Similar results were also obtained for several other a-keto acids, and also with ligands such as norphos and chiraphos. An interesting variant for the preparation of a-amino acid derivatives is the one-pot preparation of aromatic a-(N-cyclohexyla-mino) amides from the corresponding aryl iodide, cyclohexylamine under a H2/ CO atmosphere catalyzed by Pd-duphos or Pd-Trost ligands [50]. Yields and ee-values were in the order of 30-50% and 90 >99%, respectively, and a catalyst loading of around 4% was necessary. 

A synthesis of acetylalanine, from which alanine can be obtained by hydrolysis, was described in 1900 by de Jong. Pyruvic acid was neutralised with ammonium carbonate there was a considerable rise in temperature, carbon dioxide was evolved and the ammonium salt of acetylalanine crystallised out The explanation of this reaction is based upon Erlenmeyer and Kunlin s synthesis of phenylalanine from phenyl-pyruvic acid and it proceeds as follows —... 

Subject Phenylacetic Acid Mandelic Acid o-Hydroxy- phenylacetic Acid Phenyllactic Acid Phenyl- pyruvic Acid p-Hydroxy- phenylacetic Acid... 

Chemical and metabolic studies on phenylalanine. II. Phenylalanine content of the blood and spinal fluid in phenyl pyruvic oligophrenia. Ibid., 134, 105 (1940). With G. A. Jervis, D. Bolling, and E. Kanze. 

The phenanthroindolizine alkaloids can be visualized as arising by the condensation of two molecules of dihydroxyphenylalanine or one molecule of dihydroxypheny]alanine and one of t3Tosine (or their equivalents, the corresponding benzoyl acetic and phenyl pyruvic acids) with ornithine (or its equivalent, y-aminobutyraldehyde). 

Saifer, A., and Harris, A. F., Studies on the photometric determination of phenyl-pyruvic acid in urine. Clin. Chem. 6, 203-217 (1959). 

Smith, A. J., and Strang, L. B., An inborn error of metabolism with the urinary excretion of a-hydroxybutyric acid and phenyl-pyruvic acid. Arch. Dis. Childhood 33, 109-113 (1958). 

Experiments with mutants have also revealed the final stages of phenylalanine biosynthesis. Both Davis (190) and Japanese workers (459) obtained mutants excreting a labile substance, subsequently called prephenic acid, which was very readily converted into a second substance, Y, which was in turn converted into phenylalanine. Y was identified as phenyl-pyruvic acid (190). Prephenic acid was isolated (907) and its structure (see diagram 2) demonstrated (c/. 288a). 

Phenylketonuria is perhaps the best known of the diseases of amino acid metabolism. Phenylketonuria is caused by an absence or deficiency of phenylalanine hydroxylase or, more rarely, oi its tetrahydrobiopterin cofactor. Phenylalanine accumulates in all body fluids because ii cannot be converted into lymitie. Normally, three-quarters of phenylalanine molecules are converted into tyrosine, and the other quarter become incorporated into proteins. Because the major outflow pathway is blocked in phenylketonuria, the blood level of phenylalanine is typically at least 20-told as high as in normal people. Minor fates of phenylalanine in normal people, such as the formation of phenyl pyruvate, become major fates in phenylketonurics. Indeed, the description of phenylketonuria in 19v34 was made by observing the reaction of phenylpyrvivate in the urine of phenylketonurics with FeC Ij. which turns the urine olive green. 

Fig. 7.3 The simplest thrombin inhibitors, benzamidine 2 (left) and APPA, 3 p-amidino phenyl pyruvate.

Two new cephalotaxine esters having significant antileukemic activity, neoharringtonine (11) and anhydroharringtonine (12), were isolated in 1992 by Wang and co-workers (9) from C. fortunei Hook f. These authors also reported their semisynthesis from cephalotaxine and harringtonine, respectively (Scheme 31). On treatment with phenyl pyruvyl chloride in the presence of pyridine, cephalotaxine (1) produced an intermediate a-keto ester. Reformatsky reaction of this cephalotaxyl phenyl pyruvate with methyl bromoacetate yielded a mixture of neoharringtonine (11) and its epimer. 

Starting from the identification of chiral amino acids found in meteorites, a partial transfer to other biomolecules of low ee succeeded (Breslow et al. 2010 and references of Breslow cited therein). Under solvent-free conditions followed by evaporation and heating, D-a-methyl-valine reacted with pyruvate to form D-a-alanine with a relatively low ee of 3% by way of transamination. Higher enantioselectivity was observed with sodium phenyl-pyruvate. In this reaction, the D-a-methyl-valine plays two roles. It carries out the transamination that converts the keto-acid to an amino acid, while becoming a ketone after hydrolysis. Secondly, it is the source of a proton on the alpha carbon atom of the amino acid product, delivering it stereoselectively (Breslow et al. 2010). 

Lindblad, B., G. Lindstedt, and S. Lindstedt. 1970. The mechanism of enzymatic formation of homogentisate from /)-hydroxy phenyl pyruvate. J. Am. Chem. Soc. 92 7446-7449. 

The approach outlined in Fig. 16.7-6 was used for example to remove traces of d-methionine from 99% pure L-methionine116, 171 or to transform racemic phenylalanine quantitatively into D-phenylalanine and phenyl pyruvic arid1181. Coimmobilization with catalase on a solid matrix (Eupergit ) resulted in largely increased d-AAO stability. In an enzyme-membrane-reactor, space-time-yields as high as 90 g L1 d 1 were reached. In another example, a racemic mixture of D,L-erythro-P-hydroxy-histidine was converted into the ketoacid and L-erythro-P-hydroxyhistidine1191. The... 

The existence of a multiple specific enzymatic deficiency during phenylketonuria has been suggested by Boscott and Bickel (B26) to explain the abnormal excretion of aromatic acids other than phenyl-pyruvic acid, phenyllactic acid, and phenylacetylglutamine, as well as that of indolic acids. Jervis (J3) has, however, stated very recently that it is not necessary to postulate such a multiple enzymatic deficiency, since the complete biochemical urinary picture of phenylketonuria (including the presence of phenyl, hydroxyphenyl, and indolyl compounds) can be obtained temporarily in normal individuals following ingestion of large amounts of phenylalanine. 

Fig. 13.7. Two parallel yj sheets (yellow) of the protein backbone (magenta) in trypsin (ITPP) open a groove, which serves as an intercalation site for the phenyl group of the bound inhibitor p-amidino-phenyl pyruvate (red) (parallel P sheets (yellow) indicated by best planes (blue))...

Figure 8. Migration of the side chain during hydroxylation of phenylpyruvates with (hydroxy) phenyl-pyruvic acid oxidase...

The inherited disease phenylketonuria, which causes severe mental retardation, is characterized by the urinary excretion of phenyl-pyruvate, -lactate, and -acetate. How are these metabolites formed ... 

Dimethoxyphenylacetaldehyde should be formed in the normal process of deamination of 8-3,4-dimethoxyphenylalanine to 3,4-dimethoxy-phenyl pyruvic acid and decarboxylation of this keto acid. This series of hypothetical steps would explain the synthesis of tetrahydropapaverine... 

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