6-Methyluracil, oxidation

The key metabolites of caffeine (a trimethylxanthine) found in plasma, are the dimethylxanthines paraxanthine, theophylline, and theobromine the monomethylxanthine 1-methylxanthine the C-8 oxidized monomethylxanthine 1-methyluric acid and the ring oxidized uracil 5-acetyl-amino-6-amino-3-methyluracil. 

Lippert and co-workers have reported a similar series of A-,O-bridged platinum(III) dimers in which the bridging ligands are the pyrimidines, 1-methyluracil, 1-methylthymine, or 1-ethylthy-mine. Chemical oxidation of dimeric platinum(II) complexes gave [Pt2XY(L)2(NH3)4]2+, X,Y = N03", N02, H20, Cl", or Br", L=l-MeU, 1-MeT, 1-EtT. 27 t30 They too found that the HT dimers are more stable than the HH.430... 

A 1-methyluracil blue of distinctly different composition, containing (formally) two Ptn and a heterometal ion, Pdm, has likewise been prepared and structurally characterized by X-ray analysis (Scheme 5) [67]. It can be (reversibly) further oxidized to a PtnPdIVPtn state and also reduced to PtnP-d t11. There is no reason why Pt instead of Pd should not behave similarly, although this would require the loss of two NH3 ligands from a cis-[Pt(NH3)2(H20)2]2+entity. 

Disposition in the Body. Rapidly absorbed after oral administration bioavailability almost 100%. Metabolic reactions include V-demethylation and oxidation to uric acid derivatives. About 85% of a dose is excreted in the urine in 48 hours with up to 40% of the dose as 1-methyluric acid, 10 to 15% as 1-methylxanthine and up to 35% as 5-acetylamino-6-formylamino-3-methyluracil and 5-acetylamino-6-amino-3-methyluracil other metabolites excreted in the urine include theophylline, 1,7-dimethylxanthine (paraxanthine), 7-methylxanthine, and 1,3-dimethyluric acid. Less than 10% is excreted in the urine as unchanged drug. The extent of V-acetylation is genetically determined. Caffeine, theophylline, theobromine, and paraxanthine are found in plasma from dietary sources especially coffee, tea and cocoa. An average cup of coffee or tea contains approximately 100 mg of caffeine. 

Deazaflavines and pyrido[2,3-d 6,5-d ]dipyrimidines, which possess an ability to oxidize an alcohol, are obtained from 6-chloro-5-formyl-3-methyluracil and anilines or 6-aminopyrimidines [76CC203 78CPB3208 81JA5943 84TL(25) 1741 86JHC241]. This method is applied to the total synthesis of coenzyme factor 420 [90JCS(P1)253] (Scheme 100). 

Analogous ring-closure of 6-aryloxy- and 6-arylthio-l-methyluracils yields 5-deaza-10-oxaflavins and 5-deaza-10-thiaflavins, respectively. The former oxidizes benzyl alcohol under neutral (aerobic) conditions... 

Oxidation [1, 993-994, at end]. Orotaldehyde (2) can be obtained in 58% yield by direct oxidation of 6-methyluracil (1) with selenium dioxide in acetic acid.102... 

Methylated xanthines like caffeine are degraded in humans and rats by oxidative removal of methyl groups [10], Thus caffeine goes to 1,7-dimethylxanthine and 1-methylxanthine [11]. After the first demethylation there is an alternate pathway producing 5-acetylamino-6-formylamino-3-methyluracil. This pathway is more active in people with a more active acetylation system [12, 13]. There are individual, quantitative differences in the activity of this pathway in humans. In rats a major metabolite is... 

Thio-6-methyluracil. Furfural Nickel Copper chromiuln oxide 100 0 4-Methyl-6-hydroxypyrimidine 3... 

Hyvar X 5-bromo-3-sec-butyl-6-methyluracil Hyvar 5-bromo-3-isopropyl-6-methyluracil Sinbar 3- er -butyl-5-chloro-6-methyluracil Surflan 3,5-dinitro-A,iV-dipropylsulfanilamide Ansar 184 disodium methanearsonate Ansar 170 monosodium acid, methanearsonate Phytar 138 hydroxydimethylarsine oxide... 

The ab initio quantum-chemical method on the 6-31G basis has been used to study the mechanism of selenium oxide and selenous acid oxidation of 6-methyluracil to orotic aldehyde. The mixed anhydride of acetic and selenous acids, which possessed high activity and steric accessibility in electrophilic attack on position 5 of the pyrimidine ring, was formed with a gain of energy. The three-stage mechanism of the oxidation of the Me group in 6-methyluracil by the mixed anhydride of selenous and acetic acids had been analysed. ... 

All bases found in nucleic acids are derivatives of purine or pyridine. Only in some nucleoside antibiotics is an exchange of a carbon atom for a nitrogen atom, or vice versa, observed. The common bases are adenine 6-amino-purine guanine 2-amino-6-ketopurine cytosine 2-keto-4-aminopyrimidine uracil 2,4-diketopyrimidine and thymine (in DNA) 2,4-diketo-5-methylpyrimidine (5-methyluracil). Minor components found in various DNA and RNA are 5-methylcy-tosine, 5-hydroxymethylcytosine, 5-hydroxymethyluracil, 6-methylaminopurine, 5,6-dihydrouracil (in tRNA) and numerous other methylated bases (in tRNA). The bases are quite resistant to oxidation but easily attacked by nucleophilic reagents. In particular, the positions meta to the nitrogen atoms have low electron densities. Substitutions by electron donors (amino, methyl, hydroxyl) facilitate nucleophilic substitution on the other atoms. 

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