Uracils naturally-occurring

The common naturally occurring pyrimidines are cytosine, uracil, and thymine (5-methyluracil) (Figure 11.3). Cytosine and thymine are the pyrimidines typically found in DNA, whereas cytosine and uracil are common in RNA. To view this generality another way, the uracil component of DNA occurs as the 5-methyl variety, thymine. Various pyrimidine derivatives, such as dihydrouracil, are present as minor constituents in certain RNA molecules. 

Fluorouracil (5FU) is 5-fluoropyridrimidine-2,4(1/7, 3H)-dione. Its structure is illustrated in Figure 11. The hydrogen in the naturally occurring pyrimidine, uracil, is substituted by fluorine in the 5 position. The presence of the heteroatoms in the structure imparts hydrophilicity to the compound as they are capable of hydrogen bonding. 

Fig. 44 Pathways for uridylate biosynthesis. Mutants lacking enzymes PRTase or ODCase can complete a route to UMP provided by an antibody orotate decarboxylase in conjunction with the naturally occurring uracil PRTase. Decarboxylation of orotic acid [135] is thought to proceed through the transition state [136], for which the hapten [137] was developed (Smiley and Benkovic, 1994).

The four bases whose sequence determines the hereditary information in ribonucleic acid (RNA), the naturally occurring polynucleotide, are adenine, cytosine, guanine, and uracil. These structures are as shown in Figure A. 

The 13C magnetic resonance spectra have been reported for naturally occurring nucleotides 538, nucleosides,79-81,539 and uracil, thymine, 5-... 

Increased interest is added to the topic of this review by the discovery of several examples of covalent hydration in nature although no systematic investigation has been made, an increasing alertness to its possible occurrence can be detected among natural product workers. Some naturally occurring pteridines, such as xanthopterin,67 are covalently hydrated. The hydration of uracil and of the coenzyme diphosphopyridine nucleotide (DPNH) were mentioned in Section IV. 

The photoaddition of water to a variety of naturally occurring pyrimidine derivatives has been reported. Photolysis in aqueous solution of uracil (224 R = H), uridine (224 R=ribosyl), and uridylic acid results in the formation of the corresponding 6-hydroxy-5,6-dihydropyrimidine (225)208-210 these structures have been established by independent synthesis.209 Analogous photoadditions have been observed in 1,3-dimethyluracil211 and 5-fluorouracil.212 These additions are reversible. 

The diazines (pyridazine, pyrimidine, and pyrazine) are six-membered aromatic heterocycles that have two nitrogens in the ring. Cytosine, thymine, and uracil are derivatives of pyrimidine that are important bases in nucleic acids (DNA and RNA). Heterocyclic analogs of the aromatic hydrocarbon naphthalene include pteridines, which have four nitrogens in the rings. Naturally occurring pteridine derivatives include xanthopterin (a pigment) and folic acid (a vitamin). Methotrexate is a pteridine used in cancer chemotherapy. 

III. Naturally Occurring Uracils Uracils as Active Principles. 132... 

In Scheme 4, some naturally occurring and synthetic uracils are shown (84MU), most of them possessing biological activity (Scheme 4). 

The C-13 magnetic resonance spectra of the naturally occurring uracils have been interpreted in terms of the diketo structures of the compounds. Similarly the triketo structure 36 has been foundto predominate for l-(jS-D-ribofuranosyl) barbituric acid by a comparison of C-13 spectra of several model nucleosides. Also in the case of 6-hydroxycytidine the equilibrium lies strongly toward the diketo form 37b in comparison with the lactim-lactam form 37a. Very recent N-14... 

Fluorouracil (5-FU) is a fluorinated analog of the naturally occurring pyrimidine uracil, originally synthesized in the late 1950s (Table 124—11). It is a prodrug and must be metabolized to the nucleotide form, fluorodeoxyuridine monophosphate (FdUMP), to be active. In the presence of folates, FdUMP binds tightly to and interferes with... 

The most important naturally occuring diazines are the pyrimidine bases uracil, thymine and cytosine, which are constituents of the nucleic acids (see 32.4). The nucleic acid pyrimidines are often drawn horizontally transposed from the representations used in this chapter, i.e. with N-3 to the north-west , mainly to draw attention to their structural similarity to the pyrimidine ring of the nucleic acid purines, which are traditionally drawn with the pyrimidine ring on the left. There are relatively few naturally occurring pyr-azines or pyridazines. 

By far the most important naturally occurring diazines are the pyrimidinones uracil, thymine and cytosine, which, as the nucleosides uridine, thymidine and cytidine, are components of the nucleic acids, and as a consequence, a great deal of synthetic chemistry has been directed towards these types of compound in the medicinal context (33.6.3 and 33.7). (In this chapter, the designations 4-pyrimidinone and pyrimidin-... 

The structure of pseudouridine has been confirmed by two independent syntheses. Naturally occurring pseudouridine (pseudouridine C) does not yield uracil on treatment with strong acid, but treatment with N hydrochloric acid at 100° yields an equilibrium mixture of four nucleosides, designated Af, As, B, and C these arise by rearrangements of the D-ribo-furanosyl residue, and it was postulated that the A isomers are the a- and 8-D-ribopyranosyl derivatives and that pseudouridine-B is the a-D-ribo-furanosyl isomer. ... 

Analogous structures were established for the 2 -deoxynucleosides.They were not oxidized by periodate18 and could be converted into cyclonucleosides,1920 thus showing the (3 configuration. In addition the ribonucleoside uridine was converted into 2 -deoxyuridine,21 obtained by deamination of the naturally occurring 2 -deoxycytidine, via 02,2 -cyclouridine,22,23 a versatile intermediate exploited in Cambridge and elsewhere for the synthesis of 3-/I-D-arabinofuranosyl uracil (spongouridine) and other nucleosides.24 This and other cyclonucleosides are capable of a remarkable number of useful transformations. 

There are thirty-three pyrimidine derivatives identified in tobacco and tobacco smoke. The vast majority of these compounds (67%) have been identified in tobacco. Only fourteen are known to exist in tobacco smoke. As previously mentioned, the naturally occurring derivatives of pyrimidine are components of nucleic acids cytosine, thymidine, and uracil. Free pyrimidine and functionalized pyrimidine compounds in tobacco are believed to be formed from the catabolism of various nucleosides (17B21). Several of the pyrimidine-containing compounds in tobacco are agronomic chemical residues while other compounds identified in tobacco smoke are formed from those agronomic residues. 

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