1,3,7-Trimethylurate

Evidence that caffeine contributes antioxidative activity has been shown by the detection of the oxidized caffeine product, 8-oxocaffeine (1,3,7-trimethyluric acid) in roasted, ground and instant coffees, in the range 4 to 35 ppm.160... 

Stadler, R. H., Fay, L. B., Antioxidative reactions of caffeine formation of 8-oxocaffeine (1,3,7-trimethyluric acid) in coffee subjected to oxidative stress, J. Agric. Food Chem., 43(5), 1332, 1995. (CA122 289398f)... 

Occasionally O-alkylation products may be isolated. Thus ethylation at 100 °C (with ethyl iodide) of the silver salt of 1,3,7-trimethyluric acid initially gives 8-ethoxy-1,3,7-trimethyluric acid (117) which subsequently rearranges to produce l,3,7-trimethyl-9-ethyluric acid (1882LA(215)316). 

Alkylation of uric add with diazoalkanes has been reviewed (32JPR(134)310). With uric acid 1,3,7,9-tetramethyluric add is produced, presumably via an intermediate alkoxy derivative (21ZPC(117)23) since 1,3,7-trimethyluric add and 1,7,9-trimethyluric add with diazomethane at room temperature furnished 8-methoxy-l,3,7-trimethyl and 2-methoxy-... 

Dialkylated uric acids are rearranged to the so-called caffolides upon bromination in water, for example, 1,3,7-trimethyluric acid gives the 1,7-dimethylcaffolide (6), the apocaf-feine already described by E. Fischer. 

Precolumn Lichrosorb RP2 10 pm (40x2.1 mm ID), column Ultrasphere ODS 5 pm (250x4.6 mm ID), mobile phase gradient with solvent A 0.01 M sodium acetate and 0.005 M tetrabutylammonium hydrogen sulfate in water (pH 4.9), solvent B same salt concentrations in 50% methanol (pH 4.8). Gradient 0-7.5 min 0 B, 7.5-15 min 0-T5% B, 15-25 min 15-30% B, 25-33 min 30-32% B, 33-38 min 32-45% B and 38-41 min 45-0% 6. Detection UV 280 nm. Peaks 1, xanthine 2, uric acid 3, 3-methyluric acid 4, 7-methyl xanthine 5, 3-methyl xanthine 6, 1-methylxanthine 7, theobromine 8, 3,7-dimethyl uric acid 9, 7-methyluric acid 10, 1-methyluric acid 11, 1,3-dimethyluric acid 12, 1,7-dimethyl xanthine 13, theophylline 14, e-hydroxyethyltheophylline (internal standard) 15, 1,7-dimethyluric acid 16, 1,3,7-trimethyluric acid 17, caffeine, (reproduced with permission from ref. 192, by the courtesy of Journal Chromatographic Science)... 

The photooxidation of oxopurines such as caffeine, theophylline, theobromine, and 1,3,7-trimethyluric acid using Rose Bengal as sensitizer occurs by a type II mechanism. 3-Methyl-5-(methylamine)-l,5-dehydrohydantoin has been characterised as a reaction product, and evidence is presented which suggests that the initial exciplex formed between 02( Ag) and the oxopurine evolves into a zwitterionic transition state. 

Experiments with liver slices and cultured cell lines have corroborated this pathway of purine degradation. In human liver slices 16 xanthine derivatives were produced from caffeine by action of P-450 system. Demethylation at N-3 was the most prominent process [18, 19]. Comparison of cell lines from humans, hamsters, mice, and rats show some interspecies differences but all of them demethylated and oxidized caffeine [20]. Human liver cells give 1,3,7-trimethylurate as the major metabolite of caffeine, but also made were the intermediate products theobromine, theophylline, and paraxanthine [21]. Human liver microsomes convert theophylline to 1-methylxanthine, 3-methylxanthine, and 1,3-dimethyluric acid [22, 23]. Human kidney microsomes produced each of the three possible demethylated products as well as 1,3,7-... 

Noninterfering ampicillin, cefazolin, cephalothin, cephapirin, chlorotheophylline, 1,3-di-methyluric acid, genteunicin, lidocaine, methicillin, methylurea, 3-methyluric acid, quin-idine, sulfamerazine, 1,3,7-trimethyluric acid... 

Formation of methyluric acids occurs in a limited number of plant species (Figure 6.61). Radiolabeled feeding experiments indicate that theacrine is obtained from caffeine through a first oxidation and subsequent methylation of the formed intermediate 1,3,7-trimethyluric acid. Leaves of Coffea dewevrei, Coffea liberica, and Coffea Abeokuta convert caffeine to liberine, probably via theacrine and methylliberine [259,261]. 

Methyluric acids are common decomposition products of methylxanthines such as caffeine. Five such compounds (I- and 7-melhyluric acid, 1,7- and 13-dimethyl-uric acid, and 1,3,7-trimethyluric acid) were extracted from urine and sqjarated on a Cj column (A = 280nm). A two-ramp 95/5— 80/20 (at 8 min)- 70/30 (at 15 min) water (acetate pH 3.5)/methanol gradient generated excellent separation and peak shapes [375]. The linear range was 25 pg/mL to 3 mg/mL with reported detection limits of lOng/mL. 

Caffeine and four metabolites— theobromine, paiaxanthine, theophylline, and 1,3,7-trimethyluric acid—were extracted from liver tissue and resolved on a Cjg column (A = 250 nm) using an 85/15 5/95 (at 30 min hold 25 min) (895/95/7/3... 

Caffeine, 1,3- and 1,7-dimethylxanthine, and 1,3,7-trimethyluric acid were extracted fiom liver microsomes and analyzed on a 30°C Cig column (A = 278nm). The mobile phase was 96.4/1/1/1.6 water (4mM acetate buffer at pH 4)/acetonitrile/methanol/THE Elution was complete in 13 min and good resolution was obtained. Detection limits of 200nM were reported [1574]. 

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