Ribo-cytidine

JV-6-etheno deoxy and ribo adenosine (112) and 3,A -4-etheno deoxy and ribo cytidine (113), 2-thiothymidine and 2-thiodeoxyuridine (114), nucleoside analogues with long alkyl chains instead of the base, e.g. (115), and 3-nitropyrrole (116) and 4-, 5-, or 6-nitroindole... 

Conventional reversed phase HPLC is unable to separate ara-cyti-dine, ara-uridine, ribo-cytidine and ribo-uridine whereas a dual column procedure utilising an Ultrasphere ODS column in series with a Partisil PXS 10/25 SCX column gave excellent separation of these compounds (Sinkule and Evans, 1983). The accuracy of the method allowed comparative pharmacokinetic and pharmacodynamic studies to be carried out. 

By use of the Hilbert-Johnson procedure,139,140 a synthesis186 of cytidine (II) was effected this involved condensation of crude tri-O-acetyl-D-ribo-furanosyl bromide with a 2,4-dialkoxypyrimidine, followed by treatment of the crude reaction mixture with alcoholic ammonia. Although the yields were low, this achievement marked the first synthesis of a naturally occurring nucleoside. 

Thus, uridine-cytidine kinase converts uridine and cytidine to UMP and CMP, respectively thymidine kinase converts thymidine to dTMP and adenosine kinase converts adenosine to AMP. Specific kinases convert monophospho-nucleotides to dinucleotides using ATP as a phosphate donor. The conversion of diphosphonucleotides to triphosphonucleotides is carried out by a nonspecific nucleoside diphosphate kinase. This includes both the ribo- and deoxy-ribonucleotides. Cytosine and its nucleoside and nucleotide transformations are often associated with the metabolism of uracil and its nucleosides and nucleotides. Note that UTP can give rise to CTP (Figure 10.9), and also that, in the presence of cytidine deaminase, cytidine can be converted to uridine. 

The possibility that, during the alkaline hydrolysis of ribonucleic acid, tri-esters (18) - could be intermediates was ruled out on mechanistic groxmds."f > Furthermore, it was shown that the tri-ester, uridine 2 3 -(methyl phosphate) (18, R = CH3), synthesized by methylation of uridine 2 3 -cychc phosphate with diazomethane, is resistant to ribo-nuclease. f However, it has been observed that, when the benzyl ester of cytidylic acid 6 is partially hydrolyzed in acid, a significant proportion of the o isomer of this phosphoric diester is formed." ) In addition, the dinucleoside phosphates, such as adenylyl-(3 —>5 )-cytidine (14a), are also isomerized to the corresponding (2 - 5 )-dinucleoside phosphates by treatment with acid. " These studies suggest that cyclic triesters (or derivatives thereof) may be intermediates in isomerization of these phospho-diesters in acidic mediiun. 

Orengo, A. Saunders, G.R Regulation of a thermostable pyrimidine ribo-nucleoside kinase by cytidine triphosphate. Biochemistry, 11, 1761-1767... 

The kinase which converts deoxycytidine to its 5 -monophosphate has been studied most extensively in preparations from calf thymus 35, 36). The preferred substrate is deoxycytidine, for which the Michaelis constant (5 X 10 M) is much lower than that of two other substrates, deoxyadenosine and deoxyguanosine. Cytidine, uridine, and thymidine are not phosphorylated by this enzyme. Deoxycytidine kinase is subject to a complex pattern of allosteric regulation by nucleotides. The end product of deoxycytidine phosphorylation, dCTP, is a potent inhibitor this inhibition is reversed by dTTP. The enzyme has a rather broad specificity for the phosphate donor, with the triphosphates of the natural ribo- and deoxyribonucleosides being substrates the inactivity of dCTP is a notable exception. 

The rate of formation of 6,2 -anhydro-3-D-arabino-, 6,3 -anhydro-g-D-xylo-, and 6,5 -anhydro-3-D-ribo-furanosyluridines, (11)-(13) respectively, on treatment of the corresponding 5-iodouracil nucleosides with sodium methoxide has been found to be in the order of (11)>>(12)>(13), corresponding to the ease of formation of 5,6 and 7-membered rings, respectively. The ease of acid hydrolysis was in the reverse order. The same relative ease of cycliz-ation has been observed with the cytidine nucleoside analogues. 

There have been many reports of syntheses of deoxy nucleosides by standard sugar-base condensation reactions. These include 5 -deoxy-ribo nucleosides and 5 -mono- or 5",5-di-deuterated analogues, as well as derivatives of 5-deoxy-D-xylose and 5-deoxy-D-glucose, 5-alkylated thymidine derivatives, 2 -deoxy-6-methyl-5-azacytidine and its a-anomer, the thymidine analogue 4-(2-deoxy-B-D-erythro-pento-furanosyl)-6-methyl-l,2,4-triazine 3(HH)-one-1-oxide, 6-aza-3-deaza analogues of 2 -deoxy-cytidine and 2 -deoxyuridine,3 -deoxycytidine from a 3-deoxy-ribofuranose obtained from a fermentation broth producing the 3 -deoxy nucleoside antibiotic, cordycepin, 4-deoxy-DL-threo-pentopyranosyl pyrimidine nucleosides, and 5 -C-methyluridines derived from 6-deoxy-D-allose and 6-deoxy-D-talose. A range... 

The trisaccharide component of the antibiotic gonefiomycin has been shown to consist of two molecules of 2,6-dideoxy-3-0-methyl-L-(yxo-hexose, separated by one of the h-ribo-tsaiBaer A series of communications have repotted details of the bios3mthesis of ascarylose (3,6-dideoxy-L-arubino-hexopyranose), as its cytidine dijdiosphate conjugate, in Yersinia pseudotuberculosis, whoe ascarylose occurs in the O-antigen. 3-26... 

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