Phenyl hippurates

Ivanciuc, O. (1997) Artificial neural networks applications. Part 3. A quantitative structure-activity relationship for the actinidin hydrolysis of substituted-phenyl hippurates. Rev. Roum. Chim., 42, 325-332. 

Figure 13 Phenyl hippurate substrate—chymotrypsin active site complex. Dashed lines show distance constraints assigned for docking.

Figure 14 Distance-geometry-generated structures of phenyl hippurate substrate bound to active site of chymotrypsin, using constraints showed in Figure 13 and described in text. For this and the stereo triples in Figures 16—19, the left and center views are for cross-eyed viewing, while the center and right are for a stereo viewer or wall-eyed (relaxed) viewing.

Phenyl hippurate 884 Finely powdered hippuric acid (10 g) is mixed with phenol (7 g), heated on a water-bath, and treated gradually with phosphoryl chloride (6-8 g). The mixture is heated until all is dissolved, then poured into ice-water and neutralized with sodium carbonate solution. The liquid is decanted from the viscous product which is rubbed with water until fully crystalline. Crystallized from ethanol it has m.p. 104°. 

Because of the often highly specific nature of enzymatic binding sites, parameters may be position-specific. For example, Carotti et al. (1984) observed for the ficin hydrolysis of phenyl hippurates ... 

Carotti, A., Casini, G. and Hansch, C. 1984. Structure-activity relationship of the ficin hydrolysis of phenyl hippurates. Comparison with papain, actinidin and bromelain. J. Med. Chem. 27 1427-1431. 

Thiazolecarboxaldehydes exhibit many reactions typical of aldehydes. However, they give no aldolization reaction (no a-hydrogen), but they do react with different compounds such as acetic anhydride, hippuric acid, acetylglycine, and so for (37, 101, 102). Thus 2-phenyl-4-fonnylthiazole (31) mixed with hippuric acid and treated with AcOa and anhydrous NaOAc gives the azalactone (32) (Scheme 32). 

Several improved methods for the preparation of known unsaturated azlactones as well as some interesting new compounds of this type have been reported. Crawford and Little observed that the direct use of 2-phenyl-5-oxazolone (1) in the Erlenmeyer reaction gave much improved yields (35-74%) of unsaturated azlactones with aliphatic aldehydes and with ketones such as acetone and cyclohexanone [Eq, (1)], The usual procedure of mixing a carbonyl compound, hippuric acid, acetic anhydride, and sodium (or lead) acetate affords poor yields in the aliphatic series. 

The reaction of hippuric acid with a three-fold excess of trifluoro-acetic anhydride gives a 90% yield of 2-phenyl-4-(2, 2, 2 -trifluoro-l -hydroxyethylidene)-5-oxazolone (2). This compound is also obtained... 

Acetic anhydride, condensation with and acetylation of glycine, 46, 1 in cyclization of c-formylphenoxy-acetic acid to coumarone, 46, 28 in cyclization of hippuric acid to 2-phenyl-5-oxazolone, 47, 101 reaction with N-nitroso-N-phenyl-glycine to yield 3-phenylsydnone, 46,96... 

Hippuric acid, cyclization to 2 phenyl-5 oxazolone with acetic anhydride, 47,101 Holarrhimine, 46, 61 Hydrazine, reaction with cinnamalde-hyde, 47, 99... 

A further attempt has been made to develop a predictive model for chirality transfer achieved through alkylation reactions of ester enolates which feature chiral auxiliaries. " Hippurate esters (30) derived from (lI , 25 )-trani-2-(p-substituted phenyl)cyclohexanols were found, on reaction with benzyl bromide, to give (31) with predominantly the S configuration at the alkylation centre but with no correlation between the degree of stereoselectivity (20-98%) and the electron density on the aromatic ring. 

Three synthetic approaches for benzopyrones have been developed that use Gly as starting material. Hippuric acid was transformed with acetic anhydride into 2-phenyl-5(4//)oxazolone or further into its 4-ethoxy-methylene derivative, then reacted with cyclic 1,3-dicarbonyI compounds (such as like dimedone) to form 100 [90LA501 92H(33)843]. On the other hand, when hippuric acid was transformed into methyl 2-benzoyl-amino-3-dimethylaminopropenoate, it reacted with resorcinol to give a 7-hydroxybenzopyrone derivative (89JHC1273). 

Alkylation of saturated 5(4//)-oxazolones at C-4 is a well-known reaction that can be achieved under a wide variety of conditions. Numerous articles have described this reaction as a means to prepare 4,4-dialkyl-5(477)-oxazolones 147 that are valuable intermediates to prepare ot,ot-disubstituted a-amino acids. For instance,2-phenyl-5(4//)-oxazolone 146 readily obtained from hippuric acid and A,A -dicyclohexylcarbodiimide (DCC), is alkylated at C-4 with allyl, benzyl, or phenacyl halides if the reaction is conducted in dipolar aprotic solvents in the presence of weak bases. Hydrolysis of the resulting 5(477)-oxazolones leads to a,a-dialkylglycines 148 (Scheme 7.43). 

Similarly, reaction of 2-dimethylaminomethylene-3-oxoalkanoates or 2-di-methylaminomethylene-1,3-cyclohexanediones with 2-phenyl-5(4/7)-oxazolone 146, generated in situ from hippuric acid, affords 6-substituted 3-(benzoyl-amino)-2-oxo-2//-pyran-5-carboxylates 204 and 3-(benzoylamino)-7,8-dihydro-2//-l-benzopyran-2,5(6//)-diones 206, respectively. These compounds showed strong local anesthetic activity (Scheme 7.62). ... 

Ethoxymethylene)-2-phenyl-5(47/)-oxazolone 404, readily available from hippuric acid and triethyl orthoformate, has also been used as a starting material for other unsaturated oxazolones via addition-elimination reactions. Nitrogen nucleophiles are most commonly used and amines give rise to 4-(aminomethyl-ene)-2-phenyl-5(4//)-oxazolones 405 (Scheme 7.130 Table 7.37, Fig. 7.48) which, in many cases have been evaluated as antihypertensives. 

Reaction of hippuric acid and A, A -dimethylacetamide in the presence of phosphorous oxychloride affords 4-[l-(dimethylamino)ethylidene]-2-phenyl-5(4//)-oxazolone 424 " ° that is converted to 4-benzoylaminopyrazolones 425 via ring opening and cyclization with hydrazines (Scheme 7.139). " ° 4-(A, Af-Dimethyl-aminomethylene)-2-substituted-5(477)-oxazolones react similarly. 

Deacetylation of 4-[(o-acetoxy)benzylidene]-2-phenyl-5(47/)-oxazolone also immediately affords 602. The starting oxazolone was obtained by cyclodehydration of the corresponding cinnamic acid precursor or by condensation of hippuric acid with 2-acetoxybenzaldehyde in the absence of base. In examples using 2-hydroxy-acetophenone, 4-methyl-3-(acylamino)coumarins are obtained. ... 

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. 

The cited160,161 formation of polychloropyrans 120 -> 121 and 120 - 122 may be regarded as proceeding via 2-phenyl-3,4,5-trichloro- or 3,4,5-tri-chloropyrylium chlorides, which are attacked by a chloride ion. The transformation of pyrylium salts 219 to 4-formyl-4//-pyrans 220 with hippuric acid, acetic anhydride, and sodium acetate2651 is discussed in Section IV,J. 

The possibility of the triazene linking system for the ester-enolate imine condensation was initially investigated on model compounds 110 and 111 (Scheme 35). Dibenzyltriazene 110 was used as a model compound for monobactam derivatives and prepared by diazotization of hippuric acid methyl ester. Dibenzyltriazene 111 was used as a model compound for 3-phenyl-substituted azetidin-2-ones and prepared by diazotization of 2-(4-aminophenyl)-propionic acid methyl ester and conversion with dibenzylamine in 64% overall yield. The low yields of /V-unsub-stituted lactams, during the model studies, hint at a problematic transfer to solid support. 

Serum Uremic syndrome Control rats (6/5) LC-MS Indoxyl sulfate, phenyl sulfate, hippuric acid, and p-cresyl-sulfate (57)... 

This procedure is a modification of the original method of preparation of 2-phenyl-5-oxazolone3 which has since appeared in the literature in various forms.4"6 In addition to the use of acetic anhydride, the cyclization of hippuric acid to 2-phenyl-5-oxazolone has been described using phosphorus tribromide7 and N, N -dicy clohexylcarbodiimide. 8... 

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