Nucleosides cytosine, isolation

Six novel, cytosine nucleosides were isolated from the fermentation broth of S. griseochromogenes, which produces blasticidin S (55, see Scheme 22). The structural relationship between these nucleosides and cytosinine, the nucleoside moiety of blasticidin S, was investigated.87 One of these compounds was identified as l-(/3-D-glucopyrano-syluronic acid)cytosine (53). The presence of 53 was taken as evidence... 

Other degradation products of the cytosine moiety were isolated and characterized. These include 5-hydroxy-2 -deoxycytidine (5-OHdCyd) (22) and 5-hydroxy-2 -deoxyuridine (5-OHdUrd) (23) that are produced from dehydration reactions of 5,6-dihydroxy-5,6-dihydro-2 -deoxycytidine (20) and 5,6-dihydroxy-5,6-dihydro-2 -deoxyuridine (21), respectively. MQ-photosen-sitized oxidation of dCyd also results in the formation of six minor nucleoside photoproducts, which include the two trans diastereomers of AT-(2-de-oxy-/j-D-eryf/iro-pentofuranosyl)-l-carbamoyl-4 5-dihydroxy-imidazolidin-2-one, h/1-(2-deoxy-J8-D-crythro-pentofuranosyl)-N4-ureidocarboxylic acid and the a and [5 anomers of N-(2-deoxy-D-eryfhro-pentosyl)-biuret [32, 53]. In contrast, formation of the latter compounds predominates in OH radical-mediated oxidation of the pyrimidine ring of dCyd, which involves preferential addition of OH radicals at C-5 followed by intramolecular cyclization of 6-hydroperoxy-5-hydroxy-5,6-dihydro-2 -deoxycytidine and subsequent generation of the 4,6-endoperoxides [53]. 

The less basic purines generate different adducts. Both a C-8 adduct 107 and an 0-6 adduct 108 are produced in the presence of I, while the exclusive product of the reaction of A with 75n and 75o is the unique benzene imine 109. ° These purines also exhibit lower selectivity for trapping of the nitre-nium ions (Table 3). The pyrimidine nucleosides thymidine (T), uridine (U), and cytosine (C) showed negligible reactivity with these two nitrenium ions. ° The selectivity ratios for T, U, and C given in Table 3 are upper limits based on the decrease in the yield of the hydrolysis products at high nucleoside concentration (ca. 50mM). ° Since no adducts were isolated it is not clear that these selectivities represent nucleophilic trapping by the pyrimidines. 

The borohydride reduction of 2 - and 3 -ketocytidine derivatives having or lacking an N4-acetyl group provided a facile route to cytosine nucleosides labeled with tritium at specific positions of the sugar.28 Reduction of either 20a or 20c with sodium borohydride in ethanol-benzene afforded the arabino and the ribo derivatives in the ratio of 4 1. Treatment of the reduction mixture with methanolic ammonium hydroxide gave the deacetylation products, 82b and 19b, isolated in crystalline form by preparative, thin-layer chromatography. 

Nature of the Bases. The bases were readily, and hence early, identified as the purines adenine and guanine and the pyrimidines cytosine and uracil. They were isolated first by complete hydrolysis of nucleic acid, and later from the individual nucleosides. Levene showed that the two purine and the two pyrimidine bases occur in ribosenucleic acid in equimolecular proportions, and for the purines this conclusion has been confirmed. ... 

This procedure gave the desoxyribose nucleosides of guanine, cytosine, thymine, and hypoxanthine. It was later discovered by Klein that the desoxyribosylhypoxanthine had been formed from desoxyribosyladenine by the action of a deaminase of the intestine. He found that silver ions selectively inhibit this deaminase, and so was enabled to isolate the adenine nucleoside. 

The two desoxyribosylpyrimidines isolated from thymus nucleic acid are nucleosides of thymine and of cytosine. On treatment with 5% sulfuric acid, hydrolysis takes place giving the readily recognizable pyrimidine, but the sugar liberated is immediately transformed to levu-linic acid. This fact, combined with the results of elementary analysis of the two pyrimidine nucleosides, indicates that the sugar is a 2-desoxy-pentose. There is no proof that it is 2-desoxy-n-ribose. Attempts to hydrogenate thymidine by the method used for uridine have not been successful. 

Marine life can also be a rich source of medicinal material. For example, C-nucleosides spongouridine and spongothymidine isolated from the Caribbean sponge Cryptotheca crypta possess antiviral activity. Synthetic analogues led to the development of cytosine arabinoside, a useful anticancer drug. Microbes also provide extremely useful medicines, the most famous case being penicillin... 

For pyrimidine nucleosides, the ease of anhydro-ring formation by intramolecular displacement is in the order 2,2 > 2,3 > 2,5. An-hydrocytidine derivatives are formed more readily than the corresponding anhydrouridines, and N4-acylation further enhances the nucleophilicity of the cytosine residue.419 N-Acyl-2,2 -anhydro-1 -/3-D-arabinofiiranosylcytosines are also more susceptible to hydrolysis at pH 7 than either 2,2 -anhydrouridine or 2,2 -anhydrocytidine. The product isolated after p-toluenesulfonylation of a mixture containing N-acetyl-3 -5 -di-0-acetylcytidine (146) was N-acetyl-l-(3,5-di-0-acetyl-/3-D-arabinofuranosyl)cytosine (149). The 2 -O-p-tolylsulfonyl intermediate (147) presumably cyclizes, to give the 2,2 -anhydride (148), which is rapidly hydrolyzed419 to 149. 

In the case of DNA, a D-2-deoxyribose molecule is combined to each of the bases to form a nucleoside, and the nucleosides are then combined with each other with a phosphoric acid to form a polymer (DNA). On the other hand, in the case of RNA, D-ribose, instead of D-2-deoxyribose, is combined to each of the bases to form a nucleoside, and as in the case of DNA, these nucleosides are combined with each other to form a polymer (RNA). Among the bases within DNA and RNA, adenine and guanine have been described in the preceding section. In this section, cytosine, thymine, and uracil, which are pyrimidine bases, will be described. Purine derivatives exist as a constituent unit of nucleic acids and as many kinds of monomers, and these are also present in natural products, such as caffeine, inosinic acid, and cytokinin. On the other hand, as natural products, pyrimidine derivatives are rather rare. Nucleosides composed of pyrimidine bases cytosine, thymine, and uracil coupled with D-ribose are known as cytidine, thymidine, and uridine, respectively. Among these alkaloids, cytidine was first isolated from the nucleic acid of yeast [1,2], and thymidine was isolated from thymonucleic acid [3,4]. In the meantime, uridine was obtained by the weak alkali hydrolysis [5] of the nucleic acids originating from yeast. 

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