Hydroxy phenyllactic acid

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.

Benzenepropanolc acid, a-hydroxy- phenyllactic acid C6H5-CH2-CH2OH-COOH 120, 2270, 2722, 3532, 3973, 3974a ... 

Figure 5 The organic acid profile obtained for a patient with inherited tyrosinaemia. Very large concentrations of 4-hydroxy-phenyllactic acid and A/-acetyltyrosine are in evidence.

Two reactions for the production of L-phenylalanine that can be performed particularly well in an enzyme membrane reactor (EMR) are shown in reaction 5 and 6. The recently discovered enzyme phenylalanine dehydrogenase plays an important role. As can be seen, the reactions are coenzyme dependent and the production of L-phenylalanine is by reductive animation of phenylpyruvic add. Electrons can be transported from formic add to phenylpyruvic add so that two substrates have to be used formic add and an a-keto add phenylpyruvic add (reaction 5). Also electrons can be transported from an a-hydroxy add to form phenylpyruvic add which can be aminated so that only one substrate has to be used a-hydroxy acid phenyllactic acid (reaction 6). 

The following chemicals were obtained commercially (Sigma Chemical Co.) and bioassayed with C. album and Amaranthus retroflexus L. (seeds collected in North Carolina in 1980) following identification DL-3-hydroxybutyric acid (DL-3-hydroxy-butyric acid as a Na salt) and L-3-phenyllactic acid (L-2-hydroxy-3-phenyl-propanoic acid). 

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

Note that we have used the following notation for hydroxy acids in this section, -O-Gly for the glycolic acid residue -0CH2C(0)-, likewise -O-Ile is the isoleucic acid residue -OCH(CHMeEt)C(0)-, -O-Leu is the leucic acid residue -0CH(iBu)C(0)-, -O-Phe is the (3-phenyllactic acid residue -0CH(Bzl)C(0)-, and -O-Phg is the phenylglycolic acid residue -OCHPhC(O)-. 

In order to extend the two-enzyme system to other 2-hydroxy acids, a racemase with a broader activity was found in Lactobacillus paracasei. This was exploited for deracemization of 2-hydroxy-4-phenylbutanoic acid and 3-phenyllactic acid, which are important synthetic intermediates. In addition, in this case the procedure requires a kinetic resolution step and a successive racemization step. O-Acetyl derivatives of the absolute (S)-configuration can be obtained in two successive repeating cycles. Yields are around 60%. Of course the 0-acetyl derivatives of opposite configuration can be obtained when the lipase-catalyzed reaction is apphed in the hydrolysis direction. Obtaining the O-acetyl derivatives of the absolute (R)-configuration requires an additional acetylation step of the initially resolved and racemized (S)-hydroxy acid [12]. 

Silyl ethers of hydroxy amino acids have been employed in both solid-phase and solution peptide synthesis. Since the TBDMS and TBDPS ether groups are stable to piperidine and other basic reagents, these derivatives of Ser and Thr (Tables 8 and 9) can be used in the Fmoc strategy.Homodetic peptides and depsipeptides have also been synthesized using TBDMS hydroxy protection for phenyllactic acid and hydroxyisovaleric acid, respectively. 

Decarboxylation is followed by oxidative cycliza-tion to tropinone, followed by stereospecific reduction to the a-Hydroxy group, which is esterified to hyoscya-mine. The esterifying ester, tropic acid, is an intramo-lecularly rearranged phenyllactic acid (derived from phenylalanine). Further elaboration of hyoscyamine yields scopolamine (Fig. 23). The enzymes for this transformation are known. 

CbHuOj, Mr 250.25, [a +6.7° (CHCI3). A ]3-lactone from Pseudomonas syringae p v. papulans. P. is weakly cytotoxic (2-6 mg/mL show chlorotic activity while 1 mg/mL does not) and is possibly responsible for various diseases of apple and pear trees ( apple blister spots ). In addition to P. the biogenetically related methyl esters of 3-phenyllactic acid bearing hydroxy and nitro substituents on the phenyl ring are also formed. Further a-oxetanones are, e.g., ebelactones, esterastin, obafluorin, lipstatin, tetrahydrolipstatin, and valilactone. 

Deracemization of 3-phenyllactic acid and 2-hydroxy-4-phenylbutanoic acid was found to be feasible via a lipase-catalysed KR together with racemization using Lactobacillus paracasei DSM 20008 [98]. It was necessary to switch between aqueous-organic solvent systems, so it was not possible to achieve racemization in a dynamic process indeed attempts at in situ racemization in organic solvents were not successful (Scheme 4.45). 

Larissegger-Schnell, B., Glueck, S.M., Kroutil, W., and Faber, K. (2006) Enantio-complementary deracemiza-tion of ( )-2-hydroxy-4-phenylbutanoic add and (+)-3-phenyllactic acid using lipaseotalyzed kinetic resolution combined with biocatalytic racemization. Tetrahedron, 62 (12), 2912-2916. 

The same concept was used for sensing a-hydroxycarboxylic acids and diols using chiral boronate 56 (Fig. 17a) containing a displaceable fluorescent group [144]. Formation of the boronate resulted in an increased fluorescence of a couma-rin derived fluorophore, while displacement by the hydroxy acid restored the weaker emission of the free fluorophore. The enantioselective fluorescent response was sufficient for the determination of the enantiomeric excess of phenyllactic acid with a 0.13 (13%) maximum deviation from the actual values. A mathematical algorithm has recently been proposed for the calculation of both stability constants and enantiomeric excess in these indicator-displacement assays [145]. 

In Reference 58, 6-0-(2-hydroxy-3-trimethylammonio-propyl)-(3-CD (6-HPTMA-(3-CD), a highly water-soluble CD, was synthesized and used as CS for the separation of naproxen, ofloxacin, warfarin, ibuprofen, indoprofen, ketoprofen, flurbiprofen, DL-3-phenyllactic acid, mandelic acid, abscisic acid, and tropic acid. A 75-p,m i.d. fiised-sil-ica capillary (45/36 cm total/effective length) was used and the BGE consisted of a 20-mM phosphate buffer with pH... 

Isolated from the species Lyngbya semiplena collected at a shallow depth (1-3 m) in Wewak Bay, Papua New Guinea, the wewakpeptins A-D are cytotoxic depsipeptides which contain many nonribosomal amino acids such as 2,2-dimethyl-3-hydroxy-octanoic acid (Dhoaa) and 2,2-dimethyl-3-hydroxy-octynoic (Dhoya), as well as N-methy-lated amino adds such as N-methylvahne and N-methyl-alanine. A second lactone implies 2-hydroxy-isovaleric add (Hiva) for wewakpeptins A and B, and phenyllactic add (Pla) for wewakpeptins C and D. Wewakpeptins A and B are approximately tenfold more cytotoxic towards the lung cancer NCI-H460 than are wewakpeptins C and D (Han et al, 2005b). 

Hmpa 3-hydroxy-3-methyl-pentanoic acid - Lac lactic acid - Pla 3-phenyllactic acid - Pval phenylvaline... 

Piva et al. have established removable chiral tethers that attach an alkene to an enone and render the intramolecular [2-1-2]-photocycloaddition between these groups highly diastereoselective. Chiral a-and P-hydroxy acids such as (S)-lactic acid, (S)-phenyllactic acid, or (S)-mandelic acid proved to be highly effective auxiliaries. Butenyl lactate 1 was converted regioselectively to the straight adduct 2. The diastereoselectivity reached 94% DE at -40°C, albeit with a reduction in yield. At -20 C, 92% DE and 78% yield were obtained (Scheme 2). 

Free amino acids are further catabolized into several volatile flavor compounds. However, the pathways involved are not fully known. A detailed summary of the various studies on the role of the catabolism of amino acids in cheese flavor development was published by Curtin and McSweeney (2004). Two major pathways have been suggested (1) aminotransferase or lyase activity and (2) deamination or decarboxylation. Aminotransferase activity results in the formation of a-ketoacids and glutamic acid. The a-ketoacids are further degraded to flavor compounds such as hydroxy acids, aldehydes, and carboxylic acids. a-Ketoacids from methionine, branched-chain amino acids (leucine, isoleucine, and valine), or aromatic amino acids (phenylalanine, tyrosine, and tryptophan) serve as the precursors to volatile flavor compounds (Yvon and Rijnen, 2001). Volatile sulfur compounds are primarily formed from methionine. Methanethiol, which at low concentrations, contributes to the characteristic flavor of Cheddar cheese, is formed from the catabolism of methionine (Curtin and McSweeney, 2004 Weimer et al., 1999). Furthermore, bacterial lyases also metabolize methionine to a-ketobutyrate, methanethiol, and ammonia (Tanaka et al., 1985). On catabolism by aminotransferase, aromatic amino acids yield volatile flavor compounds such as benzalde-hyde, phenylacetate, phenylethanol, phenyllactate, etc. Deamination reactions also result in a-ketoacids and ammonia, which add to the flavor of... 

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