146-78-1Relevant articles and documents
The synthesis of 2-fluoropurine nucleosides
Krolikiewicz,Vorbruggen
, p. 673 - 678 (1994)
2-Aminoadenosine, obtained by silylation-amination from guanosine, is readily converted by KNO2/HF/Pyridine in up to 80% yield into 2- fluoradenosine, which is a convenient starting material for the preparation of 9(β-D-arabinofuranosyl)-2-fluoroadenine 5'-phosphate (Fludara). N6,N6- Pentamethylene-2-aminoadenosine and guanosine afford likewise the corresponding 2-fluoropurine nucleosides in high yields.
The preparative method for 2-fluoroadenosine synthesis
Berzin,Dorofeeva,Leonov,Miroshnikov
, p. 193 - 196 (2009)
The preparative method for the synthesis of 2-fluoroadenosine starting from commercially available guanosine was developed. It included the intermediate formation of 2-amino-6-azido-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl) purine, which was isolated exclu
Simple modification to obtain high quality fludarabine
Kshirsagar, Siddheshwar W.,Deshpande, Mangesh S.,Sonawane, Swapnil P.,Maikap, Golak C.,Gurjar, Mukund K.
, p. 840 - 842 (2012)
A simple and improved debenzylation process is described to obtain fludarabine in greater than 99.8% purity and 90-95% yield.
F-ara-AMP is a substrate of cytoplasmic 5′-nucleotidase II (cN-II): HPLC and NMR studies of enzymatic dephosphorylation
Jordheim, Lars,Cros, Emeline,Galmarini, Carlos,Dumontet, Charles,Bretonnet, Anne-Sophie,Krimm, Isabelle,Lancelin, Jean-Marc,Gagnieu, Marie-Claude
, p. 289 - 297 (2006)
Intracellular accumulation of triphosphorylated derivatives is essential for the cytotoxic activity of nucleoside analogues. Different mechanisms opposing this accumulation have been described. We have investigated the dephosphorylation of monophosphorylated fludarabine (F-ara-AMP) by the purified cytoplasmic 5′-nucleotidase cN-II using HPLC and NMR. These studies clearly showed that cN-II was able to convert F-ara-AMP into its non phosphorylated form, F-ara-A, with a K m in the millimolar range and V max = 35 nmol/min/mg, with both methods. Cytoplasmic 5′-nucleotidase cN-II can degrade this clinically useful cytotoxic nucleoside analogue and its overexpression is thus likely to be involved in resistance to this compound. Copyright Taylor & Francis Group, LLC.
Thermodynamic Reaction Control of Nucleoside Phosphorolysis
Kaspar, Felix,Giessmann, Robert T.,Neubauer, Peter,Wagner, Anke,Gimpel, Matthias
supporting information, p. 867 - 876 (2020/01/24)
Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose-1-phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase-catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate-specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature-dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis. (Figure presented.).
Synthesis method of isomer impurity of fludarabine phosphate
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Paragraph 0031; 0032; 0033; 0034; 0039-0042; 0047; 0048-0050, (2019/02/17)
The invention discloses a synthesis method of 2'-site isomer impurity of fludarabine phosphate, belonging to the field of pharmaceutical synthesis. The method comprises the steps of carrying out a hydrolysis reaction by using 2-fluoro-2', 3', 5'-tri-O-ace
