A-Hydroxyhippuric acid

AMINO ACIDS L-Proline. Ruthenium tetroxide. a-AMINO ALDEHYDES Diisobutylaluminum hydride. a-AMlNO ALCOHOLS Rhodium on alumina. a-AMINO-7-KETO ACIDS a-Hydroxyhippuric acid. 

H2S04 added at 0 to a stirred ice-cooled suspension of a-hydroxyhippuric acid and methyl mercaptan in glacial acetic acid, and stirred 2 days at room temp. -methylthiohippuric acid. Y 84%. F. e., also analogous esters by a related process, s. U. Zoller and D. Ben-Ishai, Tetrahedron 31, 863 (1975). 

Approximately 70% of ginkgolide A, 50% of ginkgolide B, and 30% of bilobalide is excreted unchanged in the urine (19). Metabolites isolated from human urine after administration of EGb include a 4-hydroxybenzoic acid conjugate, 4-hydroxyhippuric acid, 3-methoxy-4-hydroxyhippuric acid, 3,4-dihydroxybenzoic acid, 4-hydroxybenzoic acid, hippuric acid, and 3-methoxy-4-hydroxybenzoic acid (vanillic acid) (53). In accord with previous data, these metabolites accounted for less than 30% of the administered EGb dose. Metabolites were not detectable in blood samples. 

Vermeersch and co-workers have reported the case of a 4-month-old girl who presented with agitation, hyperexcitation, fever, dehydration, polypnea and metabolic acidosis. H NMR spectroscopy of the lyophilized urine from the patient showed the presence of 2-hydroxybenzoic acid (salicylic acid), o-hydroxyhippuric acid and 2,5-dihydroxyhippuric acid, which indicated that she had been poisoned with salicylate (aspirin). It is notable that this study was completed at 80 MHz, a relatively low field strength. 

Recently Gallice et al. used high-performance liquid chromatography (HPLC) and nuclear magnetic resonance spectroscopy (NMR) to identify a double conjugate of glucuronidate-o-hydroxyhippuric acid in ultrafiltrates of uremic plasma (G6). This compound had been previously described by Zimmerman et al. as a fraction of the so-called uremic middle molecules (Z7, Z8). So far no data have been reported on the toxicity of this compound. 

Hydroxyhippuric acid allowed to react at room temp, with benzene in coned. H2SO4 N-benzoylphenylglycine. Y 91%. F. e. s. D. Ben-Ishai, I. Satati, and Z. Berler, Chem. Commun. 1975, 349 Tetrahedron 32, 1571 (1976) a-acylamino-carboxylic acids from active methylene compds. s. Chem. Commun. 1975, 905. 

Ginkgolic acid is a mixture of several 2-hydroxy-6-alkyIbenzoic acids, two of which (alkyl = 1-octene or 3-decene) were baseline resolved on a 45 C Cjg column (A = 308nm) with a 92/7/1 acetonitrile/water/acetic acid mobile phase [1053]. Elution was complete in 6 min and peaks of interest were well resolved from all extracted material. In a separate study, Pietta et al. [1054] isolated six metabolites (hippuric acid, 4-hydroxy- and 3-methoxy-4-hydroxyhippuric acid, 4-hydroxy-, 3,4-dihydroxy-, and 3-methoxy-4-hydroxybenzoic acid) of Ginkgo biloba leaf extracts from urine and blood samples and analyzed on a Cjg column (photodiode array detector). An 88/5/5/2 water/acetonitrile/methanol/acetic acid mobile phase generated good resolution and complete elution in 15 min. The standard used was at the 1 mg/mL level. 

Although the presence of 3-hydroxyphenyl acids had been detected previously in urine, a widespread occurrence of such compounds had not been suspected before the work of Armstrong et al. (A12, A15). These acids probably arise from precursors found in the diet, as is shown by the influence of prolonged administration of chemically well-defined diets (A12), as well as by the big increase in the elimination of m-hydroxyhippuric and m-hydroxyphenylhydracrylic acids after ingestion of coffee (B22, S14). 

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