66642-55-5

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Uses

A metabolite of Azadeoxycytidine (A796950), as neoplasm inhibitor.

InChI:InChI=1/C8H13N4O7P/c9-7-10-3-12(8(14)11-7)6-1-4(13)5(19-6)2-18-20(15,16)17/h3-6,13H,1-2H2,(H2,9,11,14)(H2,15,16,17)/t4-,5+,6+/m0/s1

Upstream product

• 324018-57-7 L-Decitabine 
• 2353-33-5 5-aza-2'-deoxycytidine 

Relevant academic research and scientific papers

Facile small scale synthesis of nucleoside 5′-phosphate mixtures

We present a facile method to phosphorylate small amounts of nucleosides (0.05 mol) into mixtures of their 5′-mono-, di-, and triphosphates in a one-pot reaction. The nucleosides were first converted into their dichlorophosphates using a large excess (15-18 equivalents) of phosphorous oxychloride in trimethylphosphate. The large excess resulted in good dichlorophosphate yields (46-76%) for the four nucleosides tested. Upon the addition of tributylammonium-phosphate with additional tributylamine (20 equivalents both), the dichlorophosphate was converted into a mixture containing equal amounts of the mono-, di-, and triphosphate. The presented method was successfully applied to synthesize mixtures of stable isotope labeled nucleotides, which can be used as internal standards in quantitative mass spectrometric assays.

Unnatural enantiomers of 5-azacytidine analogues: Syntheses and enzymatic properties

Although 2'-deoxy-β-D-5-azacytidine (Decitabine) and β-D-5-azacytidine display potent antileukemic properties, their therapeutic use is hampered by their sensitivity to nucleophiles and to deamination catalysed by cytidine deaminase. As shown earlier [Shafiee M., Griffon J.-F., Gosselin G., Cambi A., Vincenzetti S., Vita A., Erikson S., Imbach J.-L., Maury G., Biochem. Pharmacol. 56 (1998) 1237-1242], β-L-enantiomers of cytidine derivatives are resistant to cytidine deaminase. We thus synthesized several 5-azacytosine β-L-nucleoside analogues to evaluate their enzymatic and biological properties. 2'-Deoxy-β-L-5-azacytidine (L-Decitabine), β-L-5-azacytidine, 1-(β-L-xylo-furanosyl)5-azacytosine, and 1-(2-deoxy-β-L-threo-pentofuranosyl)5-azacytosine were stereospecifically prepared starting from L-ribose and L-xylose. D- and L-enantiomers of 2'-deoxy-β-5-azacytidine were weak substrates of human recombinant deoxycytidine kinase (dCK) compared to β-D-deoxycytidine, whereas both enantiomers of β-5-azacytidine or the L-xylo-analogues were not substrates of the enzyme. As expected, none of the presently reported derivatives of β-L-5-azacytidine was a substrate of human recombinant cytidine deaminase (CDA). The prepared compounds were tested for their activity against HIV and HBV and they did not show any significant activity or cytotoxicity. In the case of L-Decitabine, this suggests that the enantioselectivities of concerned enzymes other than dCK and CDA might not be favourable. (C) 2000 Editions scientifiques et medicales Elsevier SAS.