Cytosine pyrimidine nucleoside formation

Figure 3. Proposed mechanism of pyrimidine nucleoside formation, a) Structures of the pyrimidine bases uracil, cytosine, and 2-pyrimidinone. Uracil and cytosine are protonated at N1 and therefore do not possess an in-plane lone pair of electrons, whereas 2-pyrimidinone does, b) The lone pair on 2-pyrimidinone nucleophilically attacks Cl of the oxonium sugar intermediate to form the glycosidic bond.

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. 

Deoxyuridine and thymidine are substrates for pyrimidine nucleoside phosphorylases, but deoxycytidine (and cytidine) is generally regarded as being inert to phosphorolysis (7) Tarris demonstration of deoxycytidine formation from cytosine in extracts of fish milt is an exception to this generalization (8). Catabolism of C3rtosine nucleosides is initiated by deamination to form uracil nucleosides which can be phosphorolyzed. 

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]. 

Prior to the definitive experiments of Friedkin and Komberg (see below), early tracer studies with orotate and with nucleoside derivatives of uracil and cytosine had demonstrated that the pyrimidine ring of DNA thymine could be derived from these compounds. In addition, it had become apparent that the methyl group of thymine was derived from one-carbon units at the oxidation level of formaldehyde rather than at the oxidation level of formate formaldehyde and the hydroxymethyl group... 

On the other hand, as seen in this chapter and in earlier chapters, the formation of phosphates of adenine (e.g., AMP, ADP, and ATP), guanidine (e.g., GTP), cytosine (e.g.,cytidine monophosphate [CMP]), uracil (e.g., uridine monophosphate [UMP]), and dTMP have all involved the carbohydrate scaffold as a building block for the formation of the finished heterocyclic base (purine or pyrimidine). It is also important to realize that, as part of nucleotide salvage pathways, it has been found that a family of enzymes collectively known as phosphorylases serves to catalyze reactions between free bases and phosphate esters of carbohydrates (and related compounds). For example, as shown in Scheme 14.13, the generalized enzyme, purine nucleoside phosphorylase (EC 2.4.2.1), catalyzes the conversion of a purine with... 

A 5-carbon sugar—a pentose—synthesized by the body in all animals, including man. Hence, it is not essential in the diet, but in the body ribose plays an important role. When it is joined with pyrimidines—cytosine, thymine, and uracil and purines—adenine and guanine—nucleosides are formed. When phosphoric acid is esterified with the nucleosides, nucleotides are formed. These compounds are then used in the formation of ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). The nucleotides of adenosine monophosphate (AMP), adenosine diphosphate (ADP), and adenosine triphosphate (ATP) are compounds that are essential to cellular metabolism. Ribose is also a constituent of the vitamin riboflavin. 

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