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.
Synthesis method of fludarabine phosphate
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Paragraph 0041-0043; 0056-0060, (2020/08/22)
The invention provides a synthesis method of fludarabine phosphate, and the synthesis route is as follows: with vidarabine as a starting raw material, fludarabine is obtained through upper protection,nitrification, fluorination denitration and deprotection, so that the fludarabine is prepared by adopting a brand-new synthesis route; meanwhile, by improving the process of phosphorylation and refining of fludarabine, the reaction time is shortened, the generation of by-products is reduced, and the product quality is improved. The method has the following advantages: 1, the initial raw materialis beta-configuration, isomer separation is avoided, and the yield is improved; raw materials are easy to obtain, the route is simple, and the price is low; 3, salification and column-passing purification and separation are avoided, so that the method is suitable for industrialization.
Synthesis method of fludarabine and nelarabine
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, (2020/01/11)
The present invention discloses a synthesis method of fludarabine and nelarabine. The method is prepared from a ribofuranose derivative as a raw material, an o-alkynyl benzoate is introduced at a 2-position hydroxyl group to obtain a key glycosyl donor, the key glycosyl donor and purine bases are subjected to a coupling reaction using a Vorbruggen glycosylation reaction to highly efficiently construct beta-nucleoside bonds, under catalysis of a gold catalyst, 2'-position ester groups are selectively removed to obtain important furyl ribonucleotide, and a bare 2' hydroxyl group is then subjected to two-step reactions of hydroxyl inversion and deprotection to respectively obtain fludarabine and nelarabine. The synthesis strategy has characteristics of being simple in operation, simple and easy to obtain the raw materials, easy in separation of products, high in reaction yield, etc., and has relatively good prospects for popularization and application.
