Ethyl hippurate

Hippuroflavin, formed by action of PCls on ethyl hippurate, is believed to be the bis-oxazolone 12. 

Serine has been prepared by the Strecker method from glycol-aldehyde 1 and from ethoxyacetaldehyde,2 3 by the condensation of ethyl formate with ethyl hippurate followed by reduction and hydrolysis,4 5 from the reaction product of chloromethyl ether with ethyl sodium phthalimidomalonate,6 and by amination of a-bromo-/3-methoxypropionic acid with subsequent demethyla-tion.7... 

The reactions of ethyl hippurate 352 with l,2-diimidoyl-l,2-dichloroethanes 353 afforded 6-imino-6//-l,3-oxazines 354 by regioselective cyclization via the carbon and oxygen atoms of the dianion formed by the dilithiation of 352... 

An anhydride [2309, 2323] (catalysed by mineral acid) or ethyl hippurate (ethyl 2-benzoylglycinate) [2186] cyclizes an o-aminophenol on prolonged refluxing. Chloral hydrate and hydroxylamine convert an aminophenol into a benzoxazole-2-carboxaldehyde oxime [2104]. 

In order to obtain basic information with regard to amino acid incorporation, Aso et al. (62) investigated a model system in which ethyl hippurate (i.e., N-benzoylglycine ethyl ester) was used as substrate instead of a protein hydrolysate. Ethyl hippurate (50mM) was first incubated with papain (1.7 X 10"2mM) at pH 6.0 and 37°C. After 15... 

Figure 3. Correlation between the initial velocities of the papain-catalyzed aminolysis of ethyl hippurate by amino add esters (abscissa) and the initial velocities (extent after 2 hr) of their incorporation during the plastein formation from an ovalbumin hydrolysate by papain (ordinate). Open circles ethyl esters. Filled drcles n-hexyl esters. Unusual abbreviations Abu = a-aminobutyric acid, Nva = norvaline.

Protein Hydrolysates. Instead of ethyl hippurate, a peptic hydrolysate of ovalbumin was used as substrate for the resynthesis reaction (64). This substrate (300 mg) was dissolved in water, adjusted to pH 6.0 with NaOH and to 0.9 ml with additional water. An amino acid ester was added to produce a 22.2mM solution and the mixture preincubated at 37°C for 15 min. Papain (3 mg), dissolved in 0.1M L-cysteine (0.1 ml), was combined with the above-mentioned preincubation mixture and incubation carried out at 37°C. After 2 hr, 0.1N NaOH (10 ml) was added to stop the enzymatic reaction and the resulting solution allowed to stand for 3 hr to hydrolyze completely the remaining amino acid ester as well as the ester group from the peptide product. The free amino acid produced from the base-catalyzed hydrolysis of the amino acid ester was determined with an amino acid analyzer. The amount of the amino acid incorporated was obtained by subtracting the determined value from the initial concentration of amino acid ester. The data obtained with the same L-amino acid esters as used in the model experiment (above) are plotted along the ordinate of Figure 3. An excellent correlation is found between the data from the model experiment and those from this experiment using a protein hydrolysate. In Table III data are shown for the extent of covalent incorporation after 2 hr of various amino acid ethyl esters into the protein hydrolysate. There is a close relationship between... 

For example, sodium cyanide reacted with 5-ethoxy-3-ethyl-2-phenyloxazolium tetrafluoroborate 1065 in the absence of a dipolarophile and unexpectedly produced ethyl hippurate (Scheme 1.282). Mechanistically, they rationalized this result by initial addition of cyanide at C(2) to produce 1066. Ring opening of 1066 then generated the azomethine ylide 1067 that, in the S-conformation, undergoes intramolecular A-deethylation to yield the ketene acetal 1068 (not isolated). Chromatographic purification of the reaction mixture effected hydrolysis of 1068 with concomitant loss of HCN and C2H5OH to produce ethyl hippurate. 

Another precursor for DALA is succinoyl chloride monomethyl ester that can undergo chain extension in the presence of hippuric acid and a base catalyst such as Y-picoline (Figure 5) (22). The initial reaction involves acylation of the dianion of hippuric acid. The resulting oxazolinone 9 can be hydrolyzed in aqueous hydrochloric acid to yield DALA. In a similar manner, succinic anhydride can serve as acylating agent when it is treated with the dianion of ethyl hippurate (23). 

Method Three, Erlenmeyer (254, 260). Ethyl formate + sodium ethylate - ethyl hippurate -> ethyl hydroxymethylene hippurate - benzoylserine ethyl ester —> serine. 

This compound is prepared from ethyl orthoformate and hippuric acid by a convenient three-step procedure, c/. ref. 1. 

Gly-OEt was also added to ethyl 3-perfluoroalkylpropynoates which were transformed in several steps into 5-perfluoroalkyl-substituted l-methyl-2-ethoxycarbonylpyrrolidin-3-ones (90X6705). 3-Propyl- and 4-propylpro-lines and 4- -pentylproline were synthesized from diethyl acetamidomalo-nate and an unsaturated aldehyde (67JA2459 72JMC1255). Ethyl benzyli-denecyanoacetate reacts with hippuric acid to give the pyrrole 8 (87H2323). 

Serine is another of the amino acids which Erlenmeyer jun. synthesised in 19O2 from hippuric acid, and which he described in detail with Storp in 1904 by condensing formic ester and hippuric ester with sodium ethylate they obtained oxymethylene hippuric ester or formyl hippuric ester —... 

The condensation of furo[3,2- ]pyrrole-type aldehydes 8g and 265-267 with hippuric acid was carried out in dry acetic anhydride catalyzed by potassium acetate as is shown in Scheme 26. The product methyl and ethyl 2-[( )-(5-oxo-2-phenyl-l,3-oxazol-5(4//)-ylidene)methyl]furo[3,2- ]pyrrol-5-carboxylates 268a-d were obtained. The course of the reaction was compared with the reaction of 5-arylated furan-2-carbaldehydes with hippuric acid. It was found that the carbonyl group attached at G-2 of the fused system 8 is less reactive than the carbonyl group in 5-arylated furan-2-carbaldehydes in this reaction <2004MOL11>. The configuration of the carbon-carbon double bond was determined using two-dimensional (2-D) NMR spectroscopic measurements and confirmed the (E) configuration of the products. 

I) ethyl bromoacetate (or any haloacetate) (II) PhthN—CH —COOC.H, [Problem 21.2(c)] (III) PhCOCI (IV) hippuric acid. PhCONHCH.COOH. 

Exposure to toluene can be detected by extracting hippuric acid from acidified urine into diethyl ether or isopropanol and direct ultraviolet absorbance measurement of the extracted acid at 230 nm. When the analysis is designed to detect xylenes, ethylbenzene, and related compounds, several metabolites related to hippuric acid may be formed and the ultraviolet spectrometric method does not give the required specificity. However, the various acids produced from these compounds can be extracted from acidified urine into ethyl acetate, derivatized to produce volatile species, and quantified by gas chromatography. 

Plasma and urine samples from atherosclerotic and control rats were comparatively analyzed by ultrafast liquid chromatography coupled with ion trap-time-of-flight (IT-TOF) MS (UFLC-IT/TOF-MS) (16). They identified 12 metabolites in rat plasma and 8 metabolites in rat urine as potential biomarkers. Concentrations of leucine, phenylalanine, tryptophan, acetylcar-nitine, butyrylcamitine, propionylcamitine, and spermine in plasma and 3-0-methyl-dopa, ethyl /V2-acety I -1. -argininate, leucylproline, glucuronate, A(6)-(A-threonylcarbonyl)-adenosine, and methyl-hippuric acid in urine were decreased in atherosclerosis rats ursodeoxycholic acid, chenodeoxycholic acid, LPC (06 0), LPC (08 0), and LPC (08 1) in plasma and hippuric acid in urine were increased in atherosclerosis rats. The altered metabolites demonstrated abnormal metabolism of phenylalanine, tryptophan, bile acids, and amino acids. Lysophosphatidylcholine (LPC) plays an important role in inflammation and cell proliferation, which shows a relationship between LPC in the progress of atherosclerosis and other inflammatory diseases. 

Acetic acid, />-Diii THyLAiaNOPHENYL>, ETHYL ESTER, 47, 69 Acetic anhydride, condensation with and acetylation of glycine, 46, 1 in cydization of o-foimylphenoxy-acetic add to coumarone, 46,26 in cydization of hippuric acid to... 

Extract sample with ethyl acetate evaporate redissolve in water (hippuric acid)... 

Esterification. Carboxylic acids are converted into their ethyl esters when heated with an excess of the reagent. Even hindered acids such as 2,4,6-trimethylbenzoic acid are esterified. An acid catalyst usually is not necessary and may be deleterious however, esterification of nicotinic acid and of hippuric acid was accomplished with p-toluenesulfonic acid in dimethylformamide. 

The most used synthetic substrates are V-benzoyl-L-Arg-ethyl ester (BAEE), N-benzoyl-L-Arg-amide (BAA), N-benzyloxycarbonyl-Lys-p-nitrophenyl ester, N-benzoyl-L-Arg-p-nitroanilide (L-Bapa), tosyl-L-Arg-methyl ester (TAME), iV-benzoyl-L-Arg-methyl ester (BAME), Gly-ethyl ester, His-ethyl ester, benzoyl-Gly-ethyl ester, L-Leu-p-nitroanilide (Leupa), L-Ala-p-nitroanilide (Alapa), L-Phe-p-nitroanilide (Phenpa), W-benzyloxycarbonyl-Arg-Arg-p-nitroanilide and jV-benzyloxycarbonyl-Arg-Arg-7-(4-methyl)coumarinylamide. Substituted ben-zoylglycine-methyl ester (substituted in position 3 or 4 of benzene, e.g., 3-cyano hippuric acid methyl ester, and N-succinyl-Ala-Met-S-benzyl-Cys-p-nitroanilide are also sensitive substrates for assaying bromelain [14,19,24,33,35,38-41] (Table 1). 

P= paracetamol PG = glucuronide PS r sulphate Alcz ethyl alcohol Hp= hippurate Glyzglycine Cr= creatine Cn= creatinine ex pansion ... 

Benzoylacetyl. See 1-Phenyl-1,2-propanedione Benzoyl alcohol. See Benzyl alcohol Benzoylaminoacetic acid. See Hippuric acid o-(Benzoylamino) diphenyl disulfide. See 2,2 -Dibenzamidodiphenyl disulfide Benzoylbenzene. See Benzophenone 2-Benzoyl benzoic acid methyl ester o-Benzoylbenzoic acid methyl ester. See o-M ethyl benzoyl benzoate 4-Benzoylbiphenyl... 

Curtius began work at Kolbe s suggestion on Dessaignes synthesis of hippuric acid (see p. 315) and at Baeyer s suggestion in Munich he used the ethyl ester of glycocoll, which he prepared. By the action of hydrochloric acid and sodium nitrite on this he discovered diazoacetic ester, the first aliphatic diazo-compound. He discovered hydrazine by the action of hot dilute acids on what he supposed was triazoacetic acid C3H3Ne(COOH)3, the sodium salt of which he obtained by the action of concentrated sodium hydroxide on diazoacetic ester.The starting material was later shown to be bisdiazoacetic... 

Years later, it was found that the reaction of ethyl formate with the ethyl ester of hippuric acid (ethyl A-benzoylglycine) in the presence of sodium ethoxide would lead to an aldol adduct, the reduction and hydrolysis of which generates racemic serine (Ser, S) (Scheme 12.40). 

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