Phenylpyruvic acid oxime

Fusetani et al. reported nine new bromotyrosine-derived metabolites, purpur-amines A-I (179-187), from P. purpurea (121). The carboxylic acid oxime units present in the bromotyrosine-derived metabolites were exclusively derived from bromotyrosines, while the oxime function in purpuramines A-I (179-183) is part of a phenylalanine moiety, which is a new variant among verongid metabolites. Phenylpyruvic acid oxime (188), which is a building block for 179-183, was also isolated from the sponge. 

Figure 55-8 Partial urine organic acid profiles 15-23 minute portion of a 33 minute run) of two patients with tyrosinemia type i. A, Acutely III patient with markedly elevated excretion of succiny[acetone, pre-NTBC treatment.The insert shows the selected ion chromatogram of the [M-15] ion of succinylacetone O-TMS-oxime TMS ester, m/z 212 B, Fifteen month old patient, succinylacetone was not detected by either total ion current (orrow) or selected ion chromatogram in three different urine specimens.This patient was later shown to be compound heterozygote for the French Canadian common splice mutation (IVS12+5G>A) and another previously unreported mutation. Peak legend I, Succinylacetone (oxime, peak I) 2, succinylacetone (oxime, peak II) 3, 4-hydroxy phenyllactic acid 4, 4-hydroxy phenylpyruvic add (oxime).The symbol marks the internal standard (pentadecanoic acid), signal abundance is normalized to the intensity of the internal standard peak.

Phenylalanine has been prepared by the action of ammonia and hydrogen cyanide upon phenylacetaldehyde,1 by the reduction of the oxime of phenylpyruvic acid,2,3 by the action of ammonia on a-bromo-j3-phenylpropionic acid,4 and by the reduction of a-aminocinnamic add or its derivatives by means of sodium amalgam with water,5,6 or red phosphorus with hydriodic acid.7,8... 

Care must also be taken, when solvent extraction is used, to avoid artefacts either from impurities in the solvent themselves (Perry and Hansen, 1974) or by the extraction of some of the non-acidic and neutral components of urine into the solvents at acid pH. These latter components include urea, phenols and alcohols, particularly those derived from dietary sources. To avoid this problem prior extraction of the urine with the same solvent systems at alkaline pH before subsequent acidification and re-extraction can be effective (Mamer et al, 1971), while the first step towards exclusion of artefacts requires the use of high-purity reagents and solvents. Although seldom incorporated into the solvent extraction methods that have been described, the prior stabilization of 0X0 acids as substituted oxime derivatives is also essential to avoid artefact formation during solvent extraction, such as the oxidative decarboxylation of phenylpyruvic acid to phenylacetic acid (Thompson etal., 1975). 

Fig. 5.18 shows the spectrum of 2-oxoisovaleric acid as its TMS-oxime derivative. The TMS groups give rise to the silyl ions at mjz 73, 75, 147, as already described, which together with M, M —15, M—43 and M-117 are also present in the spectrum of derivatized phenylpyruvic acid (Fig. 5.18). The aromatic ring helps to stabilize the molecular ion, while at the same time directing fragmentation of the benzyl bond to give mjz 91 (CeHgCH. The ion at mjz 189 is formed by the sequential loss of the ester and a methyl radical from the oxime silyl group (-CH3-CO2TMS).

Fig. 5.18 Mass spectra of the trimethylsilyl derivatives of the oximes of (a) 2-oxo-isovaleric acid and (b) 3-phenylpyruvic acid, (c) the methyloxime of 2-oxoglutaric acid, and the ethyloximes of (d) 2-oxoglutaric acid and (e) 3-phenylpyruvic acid.

Enantioselective heterogeneous catalytic hydrogenation using a chiral catalyst was pioneered by Aka-bori and Izumi, who prepared a palladium catalyst supported on silk fibroin. The oxime acetates of diethyl a-ketoglutarate or of ethyl phenylpyruvate were hydrogenated to form glutamic acid (7-15% ee) and phenylalanine (30% Similarly, a palladium-poly-L-leucine catalyst was used for the asym-... 

Fig. 4.3 Chromatogram of standard oxo acids separated as their trimethysilyl-oxime derivatives on 3 per cent OV-17 using temperature programming from 110°C to 220°C. Peak identifications are 1, pyruvate 2, 2-oxobutyrate 3, 2-oxoisovalerate 4, 2-0X0valerate 5, L-2-oxo-3-methylvalerate 6, 2-oxoisocaproate plus 7, d-2-oxo-3-methylvalerate 8, 2-oxo-4-methylthiobutyrate 9, 2-oxoglutarate 10, phenylpyruvate. (Redrawn with modifications from Sternowsky etal., 1973)...

In the MO- and EO-TMS-esters of aromatic 0x0 acids the molecular and M-15 ions are both significant (as in TMS-oxime analogues), and, although ions from loss of methoxyl or the ethoxyl radical are absent or of low abundance, a series of ions arises involving its loss. These are M-OR-CO2, M-OR-45, M-OR-CO2TMS and M-OR-HCO2TMS (m/z 190, 189, 117 and 116 respectively in phenylpyruvic-EO-TMS). It seems probable that... 

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