Cytosine deoxyriboside

Cytosine was isolated from hydrolysis of calf thymus in 1894 and by 1903 its structure was known and it had been synthesized from 2-ethylthiopyrimidin-4(3H)-one. The acid hydrolysis of ribonucleic acid gives nucleotides, among which are two cytidylic acids, 2 -and 3 -phosphates of cytidine further hydrolysis gives cytidine itself, i.e. the 1-/3-D-ribofuranoside of cytosine, and thence cytosine. The deoxyribonucleic acids likewise yield deoxyribonucleotides, including cytosine deoxyribose-5 -phosphate, from which the phosphate may be removed to give cytosine deoxyriboside and thence cytosine. 

Esterification of the 5 -hydroxyl group of deoxyribose nucleosides, such as cytosine deoxyriboside, with phosphoric acid gives the corresponding... 

SYNS CYTOSINE DEOXYRIBOSIDE dCYD 2 -DEOXYCYTIDINE DEOXYRIBONUCLEOSIDE CYTOSINE O DEOXYRIBOSE CYTIDINE DESOXYCYTIDIN (GERMAN)... 

Cytosine was first isolated in 1894 from the hydrolyzates of calf thymus. It is one of the four bases in both ribonucleic acid and deoxyribonucleic acids. Hydrolysis via the corresponding nucleotides gives cytosine deoxyriboside (2 -deoxycytidine) and cytosine riboside (cytidine), respectively. 

Fig. 11.1.3. Reversed phase HPLC of nucleic acid bases and nucleosides. Chromatographic conditions column, Spherisorb ODS-2, 5 pm (250 x 4.6 mm) mobile phase, 0.05 M monobasic ammonium phosphate, pH 3.5 flow rate, 1.5 ml/min temperature, ambient detection, UV at 260 nm. Peaks C, cytosine U, uracil FU, fluorouracil CR, cytosine riboside A, adenine CdR, cytosine deoxyriboside UR, uracil riboside T, thymine FUR, fluorouracil riboside UdR, uracil deoxyriboside, FUdR, fluorouracil deoxyriboside GR, guanine riboside GdR, guanosine deoxyriboside TdR, thymine deoxyriboside AR, adenine riboside. Reproduced from Miller et al. (1982), with...

The most important pyrimidine derivatives are those upon which biological organisms depend. Cytosine 1018 and uracil 1019 are found in ribonucleic acid (RNA) in the form of their ribonucleotides, cytidine 1020 and uridine 1021, while in deoxyribonucleic acid (DNA), cytosine and thymine 1022 are found in the form of their 2 -deoxyribonucleotides, 2 -deoxycytidine 1023 and thymidine 1024. 5-Methylcytosine 1025 is also found to a small extent (c. 5%) in human DNA in the form of its 2 -deoxyriboside 1026, and 5-(hydroxymethyl)cytosine-2 -deoxyriboside 1027 has also been detected in smaller amounts <2005CBI1>. Many variants of cytosine and uracil can be found in RNA including orotic acid 1028 in the form of its ribonucleotide orotidine 1029. Other pyrimidine derivatives to have been isolated from various biological sources include 2 -deoxyuridine 1030, alloxan 1031, and toxopyrimidine (pyramine) 1032 (Figure 2). 

Figure 4 Catalytic activation of cytosine for C5-methylation by nucleophilic addition of a thiolate at the C6 position, (a) The chemical mechanism of enzymatic DNA cytosine-S methylation. Mechanism-based inhibition of DMA MTases by cytidine analogs 5-fluoro-2 -deoxycytidine (b), 5-aza-2 -deoxy-cytidine (c), and 2-pyrimidinone-l-p-D-(2 -deoxyriboside) (d).

However, for adenine, guanine, and uracil, the dominant route of anabolism is by way of their ribonucleotide derivatives and traffic along the deoxyribosidic route is not ordinarily significant. Because cytosine is not a substrate for nucleoside phosphorylases, incorporation by the phos-phorylase-kinase route is not possible for this base. The other pyrimidine base of DNA, thymine, is poorly anabolized by both animal and bacterial cells, in spite of the fact that most cells possess thymidine phosphorylase, the action of which is readily reversible. This suggests that ordinarily cellular supplies of deoxyribose 1-phosphate are not available for base anabolism. Experiments are cited below in which it was demonstrated that a significant contribution to the biogenesis of deoxyribose of DNA in E. colt cells did not occur by a route other than ribonucleotide reduction. 

Uracil, or 2,6-dihydroxypyrimidine, was discovered in 1901 in yeast nucleic acids, and its structure was established by Fisher s organic methods. Uracil is a universal constituent of ribonucleic acids. In general, it is absent from DNA, although some bacterial DNA s have been reported to contain small amounts of uracil deoxyribosides. Cytosine, or 2-hydroxy-6-aminopyrimidine, was discovered in 1894 by Kassel and Newman. Except for the T-even bacteriophages, all DNA and RNA specimens in which the pyrimidine has been characterized contain cytosine. 

N -Deoxyribosides of cytosine and thymine were prepared biosyntheti-cally from the DNA of E. colt which had been allowed to grow on an N -containing medium (319). When isotopic deoxycjrtidine was injected into rats, it was not incorporated into RNA pyrimidines, which indicated that the transformation of cytidine to deoxycytidine was not reversible (330). However, labeled deoxycytidine served as a precursor of both DNA thymine and cytosine, while labeled thymidine was found solely in thymine. Thus, the conversion of deoxycytidine to DNA thymine was another irreversible step. 

Bosch et al reported the Pd-catalysed amidation of 2,6-dihalopurine nucleosides (16-18). The authors compared the reactivity of 2-Cl, 2-Br and 2-1 derivatives of a 6-chloropurine rihose-protected nucleoside with various amides and carbamates, under Buchwald conditions, between 0 and 110 °C. The reactivity order was 2-I>2-Br>6-Cl 2-Cl. The 2-iodo substituent could be replaced even at 0 °C while the replacement of 2-Cl substituent required 110 °C. Adamska et al reported the synthesis of A/ -derivatives of adenine and A/ -substituted derivatives of cytosine and their 2-deoiyribosides using unprotected nucleobases (adenine and cytosine) or unprotected 2-deoxyribosides with high yields. 

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