Oxonic acid

The name 5-azaorotic acid should be given to allantoxanic (oxonic) acid but it is not yet commonly used. The elucidation of the correct structure of this compound was closely linked to the solution of the course of oxidation of uric acid mentioned earlier. 

The structure (5) originally proposed by Ponomarev appeared to be confirmed by the conversion of dihydrooxonic acid to allantoin performed by Biltz and Giesler. Biltz and RobP showed later that oxonic acid is identical with allantoxanic acid obtained on oxidation of allantoin. Since that time both these trivial names are in usage. 

Works on the oxidation of uric acid has unequivocally established the triazine structure > ° (9) of oxonic acid. This is further confirmed by the straightforward synthesis described by Piskala and Gut. ° The reaction of biuret (11) with potassium ethyloxalate yielded a potassium salt (24), that with ethyl oxamate, the amide of oxonic acid (25). Both these compounds were converted to 5-azauracil. An analogous reaction with diethyloxalate which should produce an ester of oxonic acid resulted in a mixture of urethane and parabanic acid, however. 

Hence, by this pathway the formation of allantoin is not at variance with the triazine structure of oxonic acid. 

Shirasaka T, Shimamoto Y, Fukushima M. Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its anti-tumor activity in rats. Cancer Res 1993 53 4004 009. 

Yii TF, Gutman AB, Berger L, Kaung C (1971) Low uricase activity in the Dalmatian dog simulated in mongrels given oxonic acid. Am J Physiol 220 973-979... 

The isolation of allantoin (7), after lead peroxide oxidation of uric acid was followed by the recognition of other oxidation products, the main product of which are oxonic acid (8), allantoxaidine (9) and oxaluric acid (HjNOCHNCOCOjH). Their structures have been clarified by comprehensive studies using isotopically labeled compounds. ... 

Eiteman, M.A. Gordillo Cabrera, M.L. Analysis of oxonic acid, uric acid, creatine, allantoin, xanthine and hypoxanthine in poultry litter by reverse phase HPLC. Fresenius J. Anal. Chem. 1994, 348, 680-683. 

Oxonic acid amide, C4H4N403, microcrystalline substance. Practically in sol in organic solvents, sparingly sol in boiling water Does not melt below 350. darkens above 300. ... 

Azaorotic (oxonic) acid represents another analogue of orotic add with cytostatic activity [274]. The drug inhibits metabolic transformation and incorporation of orotic acid in the liver and kidney [275]. Similarly to... 

Xanthine, creatine, allantoin, oxonic acid, uric acid, and hypoxanthine were extracted from poultry litter and separated on a Cjg column (A = 200 nm, 215 nm, 235 nm, 290 nm). Elution was complete in 25 min using an aqueous 50 mM monobasic potassium phosphate mobile phase [1575]. Xanthine and hypoxanthine were poorly resolved. Standards of 20 mg/mL with 20 pL injections were easily detected. 

Purine synthesis de novo was gauged by the rate of ( C) formate incorporation into total purines produced (10). 1 mM oxonic acid was added to block allantoin formation (11). 

Brandenberger, H. 1954. The oxidation of uric acid to oxonic acid (allantoxanic acid) and its application in tracer studies of uric acid biosynthesis. Biochim. Biophys. Acta. 15 108. 

Renal Disease is a well recognized complication of gout, and the typical histologic features of chronic gouty nephropathy have been carefully studied, however, early evolution of the nephropathy and its precise relationship to hyperuricemia and uricosuria have been difficult to study in the human subject. Unfortunately, animal models of sustained hyperuricemia are difficult to produce and maintain. Recently, Stavric and colleagues described the production of hyperuricemia and urate nephropathy in rats fed orally with oxonic acid and uric acid, oxonic acid is a potent, hepatic uricase inhibitor and this chemical, combined with uric acid or RNA dietry supplements, consistently leads to hyperuricemia in this species. 

After three weeks on the diet containing oxonic acid and uric acid the following biochemical features were detected. There is clearly a statistically significant hyperuricemia, increased urinary urate concentration and increased tissue urate deposition. 

EFFECTS OF ALLOFURINOL AND OXONIC ACID ON FYRIMEDINE METABOLISM IN THE PIG... 

Oxonic acid is a uricase inhibitor (6) and has been given to rodents to produce an animal model for gout (7). When given to pigs urinary allantoin excretion decreased, as uric acid excretion increased. These findings indicate inhibition of the enzyme uricase. However, oxonic acid also produced a great increase in orotic acid and orotidine excretion. Urinary levels increased from 5 nig to 900 mg/2A hours, and this would imply a complete or... 

Thesefindings cast considerable doubt on the suitability of oxonic acid as an agent for the production of an animal model in the study of gout. 

Many potent pyrimidine antagonists have also been obtained by isosteric replacement in the heterocyclic ring. Oxonic acid (Fig. 12) an analogue of orotic acid, prevents the conversion of the latter to orotidylic acid (Fig. 2). A later stage of pyrimidine biosynthesis, the decarboxylation of orotidylic acid to form uridylic acid (Fig. 2) is strongly inhibited by 6-azauracil (Fig. 12 this chemical should be correctly termed 4-azauracil). The riboside of 6-azainacil acts on the same pathways as the base, but its inhibition of the orotidylate carboxylase enzyme is some 20 times more potent... 

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