Compounds, labeled pyrimidine derivative

Labeled compounds have also been produced by the hydrolysis of reduced pyrimidine derivatives, and thus the basic hydrolysis of 5,5,6,6-tetradeuterouracil 547 (R = D) gave 2,2,3,3-tetradeutero-/5-alanine 548 (R=D) in 50% yield <2001JLR7>. 5,6,6-Trideuterothymine 547 (R = Me) behaved similarly to give 2,3,3-trideutero-3-amino-2-methylpropanoic acid 548 (R = Me), also in 50% yield <2001JLR7>. Similar procedures have been performed with tritiated uracil derivatives <2002MI295>. 

Uracil derivatives can be nitrated at C-5 under conditions that allow retention of a sugar residue at N-1 Nitration at N-3 can also be achieved N-3-nitro-compounds react with amines via an ANRORC mechanism, with displacement of nitramide and incorporation of the amine as a substituted N-3, as shown below. This seqnence has been ntilised to prepare N-3-labelled pyrimidines (31.2.2). An analogous ANRORC process takes l-(2,4-dinitrophenyl)-uracils to 1-arylamino-uracils by reaction with arylamines at room temperatnre. ... 

Extensive investigation of amide-induced amination of purine and its derivatives has shown that the parent compound (purine) as well as its 2-methyl and 8-methyl derivatives react with potassium [ - Njamide in ammonia to undergo exclusive amination at C6 without incorporation of the N label into the ring (Chichibabin reaction). Amination of 2-fluoro-, 2-chloro-, and 2-(methylsulfanyl)purine 7, and 2-chloro-6-phenylpurine with potassium [ N]amide in ammonia, however, gives purin-2-amines with complete incorporation of the N label in the pyrimidine ring. 

Uric acid that is produced in man is essentially the product of the action of the enzyme xanthine oxidase on xanthine and hypoxanthine. A tiny amount of uric acid may be ingested as part of the diet, but the great bulk is the result of the action of this enzyme on these two purines. These purines are themselves produced either as a result of the breakdown of cellular material in toto, the turnover of nucleic acids in the cells, or as a result of the intermediary metabolism of various purine nucleotide derivatives. These latter compounds are active in the flow of energy, in methyl group transfer reactions, and as part of the functional molecule of many vitamins. There is direct and indirect evidence that some of the uric acid derives from all these sources. Essentially this evidence consists of the demonstration that other parts of the nucleie acids are found in the urine, such as pyrimidine breakdown products (P9) and methylated purines, which are found only in nucleic acids. There is also isotopic evidence that some labeled purines appear in the urine too quickly after administration of radioactive precursors... 

In the area of 2, 3 -didehydro-2, 3 -dideoxynucleosides, a new route to compounds of this type in the pyrimidine series is outlined in Scheme 4. The thioglycoside 54 was produced directly from deoxyribose and thiophenol in acidic conditions, and the condensations to form the nucleoside derivatives were P-selective by about 2 l/ A full account has been given of the formation of 2, 3 -didehydro-2, 3 -dideoxy systems from 2, 3 -dimesylates, protected at 0-5, by treatment with telluride anion (see Vol. 27, p. 247)7 Treatment of the furanoid glycal 55, made by cyclization of an acetylenic alcohol (Chapter 13), with silylated thymine in the presence of iodine, followed by sodium methoxide, provides a new route to d4T (56)7 A new synthesis of d4T (56) from 5-methyluridine has also been described, as has a route to d4T labelled with at C-1, which starts from [l- C]-ribose and proceeds via [r- C]-5-methyluridine, convertible in very high yield to [l - C]-d4T. ... 

A. The Measurement of Isotopes. B. The Synthesis and Degradation of Labeled Compounds (Including. Application to Metabolic Studies) Monosaccharides and Polysaccharides Citric -Acid Cycle Intermediates Glycolic, Glyoxylic and Oxalic Acids Purines and Pyrimidines Porphyrins Amino. Acids and Proteins Steroids Methylated Compounds and Derivatives Sulfur Compounds Fatty. Acids Phospholipids Coenzymes lodinatftd Compounds Intermediates of Photosynthesis 0 -Labeled Phosphorus Compound. . 

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