Cytosine derivatives

The proton transfer in these clusters via the water bridge was found to be about three times as fast as a nonassisted transfer, underscoring the importance of the solvent for the reaction mechanism [98IJQ855]. In addition to the relative stabilities of the cytosine tautomers, the structures and properties of some cytosine derivatives have been investigated, mainly those of 5-hydroxycytosine 111 and 5,6-dihydroxycytosine 112 (Scheme 73) [99JST1, 99JST49]. 

Gemcitabine (Fig. 7) is a cytosine derivative that is very similar to ara C. It undergoes metabolic activation to difluorodeoxycytidine triphosphate, which interferes... 

The coordination properties of pyrimidine bases seem to be less versatile than those of purine derivatives. Various Pt(II) and Pt(IV) compounds, including cis- and rrans-DDP, preferentially bind to the N3 site in N1-substituted cytosine derivatives (Figure 7), as verified by a variety of methods [7]. Simultaneous binding to N3 and to the exocyclic amino group C(4)-NH2 upon loss of a proton has been observed in a bridged Pt(II) system and in a chelated Pt(IV) system [7]. With 1,3-di-methyluracil, Pt(II) coordination to the C5 atom has been ascertained by X-ray crystallography [22]. 

Sulfoxides have also been used in the synthesis of nucleoside analogs (Scheme 3.2). Chanteloup and Beau reported the synthesis of ribofuranosyl sulfoxide 13 and its use in the glycosylation of a series of silylated pyrimidine and purine bases.7 Although 16 is not an anomeric sulfoxide, its reaction with cytosine derivative 17 is conceptually related.8... 

Schwendener RA, Schott H. Lipophilic arabinofuranosyl cytosine derivatives in liposomes. Methods Enzymol 2005 391 58. 

Also the preparation of the tumour imaging agents 5-[ F]fluorocytosine [108] (Scheme 28) and cytosine derivative [ F]capecitabine [109] can be considered as a direct /7eferoaromatic electrophilic dehydrogenation. 

Reduction of cytosine produces a radical with sites of unpaired spin density at C2, C4, and C6. The hyperfine coupling of the unpaired spin with the C6-H produces a — 1.4-mT doublet, which is the main EPR feature of one-electron reduced cytosine observed in various cytosine derivatives [21]. 

Electrodes based on neutral cytosine derivative 10a (1.3 wt%) and 9 (150 mol% relative to 10a) gave EMF slopes of-29 mV decade" for both 5 -GMP and5 -AMP (Figure 8b), suggesting that these electrodes respond in a Nemstian manner to nucleotides in their divalent form, just as in the case of the anion exchanger electrode. The potentiometric response was selective for 5 -GMP over 5 -AMP with... 

Figure 8. Potentiometric responses to 5 -CMP (o) and 5 -AMP ( ) by PVC matrix liquid membranes (DOP/PVC = 2 1 wt/wt) containing (a) lipophilic cation 9 (3.1 wt%) and (b) lipophilic cation 9 (3.1 wt%) plus neutral cytosine derivative 10a (1.3 wt%) (150 mol% 9 relative to 10a). Measured at pH 6.8 (0.1 M HEPES-NaOH buffer) (adapted with permission from Anal. Chim. Acta 1997, 341, 134. Copyright 1997 Elsevier Science Ltd.).

Figure 12. Concentration dependence of the responses to 5 -GMP and 5 -AMP of the oriented membranes based on (a) cytosine derivative 10b, (b) thymine derivative 11b, and (c) cytosine derivative 22. The response factor, R(sample), is expressed by the decrease in the oxidation peak current (/e) upon analyte addition [/ (sample) = [/p(blank) - /p(sample)]//p(blank)l. Measured at 20 °C with a 0.1 M phosphate buffer solution (pH 6.0, 20 °C) containing 1.00 mM [FeICNIel .

Adducts 119 are of relevance as reaction intermediates in the chemistry of several uracil and cytosine derivatives, which show a strong tendency to undergo covalent nucleophilic addition across the 5,6 double bond with such reagents as water, alcohols, hydroxylamine, and bisulfite ion. 

Cytosine Derivatives. l-/j-D-Arabinoiuranosylcytosine (ara-C). G)H 3N3C>5 reportedly has had significant therapeutic effects in patients with localized herpes zoster, herpes eye infections, and herpes encephalitis. although several negative results have also been reported, Ara-C. also known as cytarabine. is quite toxic and is only recommended for very severe viral infections. A number of derivatives of ara-C have been prepared in an effort to improve on antiviral activity and to reduce the toxicity. 

Assignment of the weakly acidic group (pK 10.4) of amicetin to the amide linkage between cytosine and p-aminobenzoic acid was confirmed163 by the synthesis of JV-benzoyl-1 -methylcytosine (XLIa) by benzoylation of 1-methylcytosine. This cytosine derivative (XLIa), upon titration,... 

Spectra recorded at 220 MHz have allowed determination of the chemical shifts and coupling constants for H-l and H-2 of the various ring and anomeric forms78 and cytosine derivatives (17, 18, 19, and 20)79 of 2-deoxy-2(S)- and 2(R)-deuterio-D-en/ firo-pentose (21 and 22), and have also simplified interpretations of the spectra of methyl 2-deoxy-/3-D-en/ffiro-pentofuranoside80 (23) and various deoxyhalo-... 

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