Uridine cytidine and

Mixtures of photolabile 2 - and 3 -0-(2-nitrobenzyl)ribonucleosides were obtained in good yields when adenosine, uridine, cytidine, and inosine were treated with 2-nitrophenyldiazomethane in the presence of tin(II)chloride [362]. The dibutylstan-nylene approach has been used for the preparation of 2 -(4-nitrobenzyl)uridine [366]. 2-Nitrobenzyl chloride and sodium hydride in DMF gave the 2 -ethers in 26-37% yield, depending on the starting nucleoside [363, 367]. 

If we attach the nitrogenous bases to a ribose, we have the RNA nucleosides. The four RNA nucleoside bases are adenosine, uridine, cytidine, and guanosine. Usually, these nitrogenous bases are represented as A, U, C, and G, respectively. Figure 12.69 gives the names and structures of these compounds. Addition of a phosphate group to carbon 5 of the ribose sugar affords the RNA nucleotide bases. 

The syntheses of carbocyclic analogs of phosphononucleosides (29) and (30a-c) have been reported. Phosphonic acid (29) was obtained by introduction of the benzoylated thymine on the 2(4-hydroxycyclopent-2-enyl)ethyl phosphonic acid diisopropyl ester under Mitsunobu conditions while (30a-c) were prepared by building-up the base around a phosphono-cyclopentylamine moi-ety. The vinylphosphonate derivatives of uridine, cytidine and cytosine ara-binoside (31a-c) have been prepared by Wittig condensation of [(diethoxyphos-phinyl)methylidene]triphenylphosphorane with the appropriately protected 5-aldehydic nucleoside derivatives. Dihydroxylation of the novel vinyl phosphon-ates offered the dihydroxylated phosphonate derivatives (32a-c). Each of these novel compounds was evaluated as substrates for the enzyme nucleotide monophosphate kinase, and their toxicity to K562 cells. All analogues were found to be poorly phosphorylated by the kinase and exhibited poor in vivo toxicity. ... 

Cyanoethyl 2-pyridyl phosphate and uridine-, cytidine-, and adenosine-5 -phosphates give the / ./ -pyrophosphate diesters (XII-610) which can be converted to the pyrophosphate with base. ... 

Deoxy-6,2 -methano-pyrimidine nucleosides are accessible by a sequence including Peterson olefination and intramolecular glycosidation, as outlined in Scheme 3 (for an earlier route, see Vol. 19, p. 198-9). Intermediate (19) can be transformed into the uridine, cytidine and 4-thiouridine systems. 8... 

In most of these reactions adenine nucleotides are employed although reactions involving nucleotides of the uridine, cytidine, and guanosine series are well known. It should be noted that nucleosides themselves and nucleotide monophosphates are surprisingly inactive in biosynthetic processes. Thus, nucleoside kinases, monophosphate kinases, and diphosphate kinases, which convert nucleoddes and nucleoside monophosphates to the di- and triphosphate stage are incUqiensable for cellular bio yntheds. 

Jimg K-Y, Hohl RJ, Wiemer AJ, Wiemer DF (2000) Synthesis of phosphonate derivatives of uridine, cytidine, and cytosine arabinoside. Bioorg Med Chem 8 2501-2509... 

FIGURE 11.11 The common ribonucleosides—cytidine, uridine, adenosine, and guanosine. Also, inosine drawn in anti conformation. 

We also examined separation by 32 (A-DEAE cell) and T-DEAE cell. Uridine was more retarded by 32 (A-DEAE cell) than cytidine, and uridine more than adenosine. These results strongly suggested the existence of the hydrogen-bonding of A-U pairs. On the T-DEAE cell, adenosine was found to be more retarded than... 

After silylation-amination in situ transsilylation (cf Section 2.3) of the intermediate persilylated cytidines 5 with excess boiling methanol for 3-5 h gives the desired free cytidines 6 and methoxytrimethylsilane 13a (b.p. 57°C) [13]. Thus protection of the alcohohc hydroxyl groups of the ribose moiety and silylation-activation of the 4-position in the pyrimidine moiety in persilylated uridine 3, and the concomitant amination of 3, aU in one reaction step, to 5 is followed finally by in situ transsilylation (cf. Section 2.3) with excess boihng methanol in one reaction vessel. 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

In ref. [178] other tri(azolyl)phosphines are used for the synthesis of uridine-, adenosine-, and cytidine-oligoribonucleotides according to this method, with azolyl groups... 

The increase in erythrocyte destruction may be due in part to inhibition by lead of pyrimidine-5 -nucleotidase, which results in an accumulation of pyrimidine nucleotides (cytidine and uridine phosphates) in the erythrocyte or reticulocyte. This enzyme inhibition and nucleotide accumulation affect erythrocyte membrane stability and survival by alteration of cellular energetic (Angle et al. 1982 EPA 1986a). Formation of the heme-containing cytochromes is inhibited in animals treated intraperitoneally or orally... 

Outstanding in this field has been the contribution of Todd and his co-workers. The significance of their work has been, first, that it has led to successful syntheses of adenosine, guanosine, cytidine, and uridine. Equally important, however, has been its contribution toward the final confirmation of the structures of the nucleosides. This may be illustrated in the following way. By the route I to V, which had been developed for the synthesis of pentosylpurines (purine 1-deoxypentosides), it was possible to obtain 9-/3-n-mannopyranosyladenine (V), in which the position of the carbohydrate residue was known with certainty.19 This nucleoside, on oxi-... 

Table XIX contains stability constants for complexes of Ca2+ and of several other M2+ ions with a selection of phosphonate and nucleotide ligands (681,687-695). There is considerably more published information, especially on ATP (and, to a lesser extent, ADP and AMP) complexes at various pHs, ionic strengths, and temperatures (229,696,697), and on phosphonates (688) and bisphosphonates (688,698). The metal-ion binding properties of cytidine have been considered in detail in relation to stability constant determinations for its Ca2+ complex and complexes of seven other M2+ cations (232), and for ternary M21 -cytidine-amino acid and -oxalate complexes (699). Stability constant data for Ca2+ complexes of the nucleosides cytidine and uridine, the nucleoside bases adenine, cytosine, uracil, and thymine, and the 5 -monophosphates of adenosine, cytidine, thymidine, and uridine, have been listed along with values for analogous complexes of a wide range of other metal ions (700). Unfortunately comparisons are sometimes precluded by significant differences in experimental conditions.

In contrast to uridine,389 cytidine does not yield a 5 -chloro-5 -deoxy derivative on reaction with N,N-dimethyl(chlorometh-animinium) chloride instead 2,2 -anhydrocytidine is formed.395 However, thionyl chloride or bromide in hexamethylphosphor-amide at room temperature achieves this selective replacement of the primary hydroxyl group of halogen in cytidine, and also in adenosine, in respective yields of 80 and 75% for the chloro compounds, and 55 and 30% for the bromo analogs.396... 

In nature, eight common nucleotides exist, four found in DNA and four in RNA. In the standard abbreviations for DNA nucleotides, a lowercase d specifies the presence of deoxyribose. RNA nucleotides lack this designation. Nucleosides have names of one word (e.g., deoxyadenosine, cytidine, and uridine). The ending monophosphate completes the nucleotide names. Table 16.1 lists correct names for all common nucleotides and nucleosides, and Figure 16.9 shows linkages and structures for all eight nucleotides. 

Nature has exploited ribose derivatives for a number of cmcially significant biochemicals. Many of these contain a heterocyclic base attached to the P-anomeric position of o-ribofuranose, and are termed nucleosides. Adenosine, guanosine, cytidine, and uridine are fundamental components of ribonucleic acids (RNA see Section 14.1),... 

RNA polymerase, and the triphosphates of the purine ribonucleosides, uridine, and cytidine, and otherwise the same conditions, will prime the synthesis of RNA. The amounts of synthetic DNA or RNA are many fold greater than the amount of primer DNA the DNA product is nearly the same in most measurable ways as the primer DNA. The efficiency of the DNA in initiating these syntheses is known as the primer activity of the DNA, and can be affected by alterations of the bases which compose the nucleic acid, and by other factors. 

Candida utilis is grown to high biomass concentrations and the extracted RNA is subsequently hydrolysed into the four 5 nucleotides adenosine 5 -monophosphate (AMP), GMP, cytidine and uridine 5 -monophosphate by crude nuclease PI from Penicillium the desired nucleotides are isolated by ion-exchange chromatography and AMP is converted to IMP by adenyl deaminase from Aspergillus [22, 36]. 

The similarity in the pyrimidine carbon resonances in cytidine and deoxycytidine is indicative of the independence of these shifts from the sugar fragments. The differences observed between the chemical shifts of uracil and thymine, or uridine and thymidine, indicate that they must result from the presence of the 5-methyl group in the latter. The downfield shifts ( — 7.5 ppm) of the 05 peaks of uracil or uridine upon 5-methyl substitution are typical for a carbon directly substituted by a... 

Figure 5-5 Near ultraviolet absorption spectra of cytidine, uridine, adenosine, and guanosine. 1. Monoprotonated form of cytidine (for which pKa = 4.2). 2. Neutral form (pH 7) of cytidine. 3. Neutral form of uridine (for which pKa = 9.2). 4. Monoanionic form of uridine. 5. Monoprotonated form of adenosine (pKa = 3.5). 6. Neutral form of adenosine. 7. Neutral form of guanosine (pKa = 9.2). 8. Monoanion of guanosine.

Comparison of the spectrum of uridine with data of 4-thiouridine, 2,4-dithiouridine, thymidine, 4-thiothymidine, cytidine and 2-thiocytidine allows the assignment of all carbon resonances of these pyrimidine moieties. Further confirmation of these assignments is obtained from the proton off-resonance decoupled 13C-spectra of these nucleosides, as has been demonstrated for thymidine The pyrimidine CH3 and CH resonances of the proton broadband-decoupled spectrum are split into a quartet and a doublet, respectively, in the proton off-resonance spectrum, and can thus be easily assigned. 

The first scientific articles from the IKhPS were submitted for publication in the early 1960s, among them being Nikolay s reports on his work in the new field. His major project in nucleotide chemistry was specific chemical modifications of heterocyclic bases. Reactions of hydroxylamine with cytidine and uridine were studied in detail and a new reagent, O-methylhydroxylamine, was proposed for modification of cytidine. These investigations aimed at the development of efficient methods for sequencing and analysis of the secondary structure of polynucleotides. Later, a reaction of chloroacetaldehyde with adenosine and cytidine was discovered and used for preparation of fluorescent polynucleotide derivatives. 

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