Identification | Back Directory | [Name]
2'',3'',5''-Triacetyl -azacytidine | [CAS]
10302-78-0 | [Synonyms]
Nsc291930 2',3',5'-triacetyl-5-Azacytidine 2'',3'',5''-Triacetyl -azacytidine S-Triazin-2(1H)-one, 4-amino-1-.beta.-D-ribofuranosyl-, triacetate (ester) 1,3,5-Triazin-2(1H)-one, 4-aMino-1-(2,3,5-tri-O-acetyl-b-D-ribofuranosyl)- 1,3,5-Triazin-2(1H)-one, 4-amino-1-(2,3,5-tri-o-acetyl-.beta.-D-ribofuranosyl)- (2R,3R,4R,5R)-2-(Acetoxymethyl)-5-(4-amino-2-oxo-1,3,5-triazin-1(2H)-yl)tetrahydrofuran-3,4-diyl diacetate | [Molecular Formula]
C14H18N4O8 | [MDL Number]
MFCD11113159 | [MOL File]
10302-78-0.mol | [Molecular Weight]
370.316 |
Chemical Properties | Back Directory | [Appearance]
White to off-white powder | [Boiling point ]
497.3±55.0 °C(Predicted) | [density ]
1.60±0.1 g/cm3(Predicted) | [storage temp. ]
Store at 0-5°C | [solubility ]
≤30mg/ml in ethanol;30mg/ml in DMSO;30mg/ml in dimethyl formamide | [form ]
crystalline solid | [pka]
3.06±0.20(Predicted) | [InChI]
InChI=1/C14H18N4O8/c1-6(19)23-4-9-10(24-7(2)20)11(25-8(3)21)12(26-9)18-5-16-13(15)17-14(18)22/h5,9-12H,4H2,1-3H3,(H2,15,17,22)/t9-,10-,11-,12-/s3 | [InChIKey]
OTQJVHISAFFLMA-IOCWGDCUNA-N | [SMILES]
[C@H]1(O[C@@H]([C@@H](OC(C)=O)[C@H]1OC(=O)C)COC(C)=O)N1C(=O)N=C(N)N=C1 |&1:0,2,3,8,r| | [CAS DataBase Reference]
10302-78-0 |
Hazard Information | Back Directory | [Chemical Properties]
White to off-white powder | [Uses]
5-Azacytidine is an inhibitor of DNA methyltransferaes, potentially serving to reverse epigenetic changes. It reduces hypermethylation associated with certain diseases, including myelodysplastic syndromes and cancer. 2’,3’,5’-triacetyl-5-Azacytidine is a prodrug form of 5-azacytidine that may be rapidly absorbed orally without formation of major metabolites in the gastrointestinal tract.[Cayman Chemical] | [Description]
5-Azacytidine is an inhibitor of DNA methyltransferase, potentially serving to reverse epigenetic changes.1 It reduces hypermethylation associated with certain diseases, including myelodysplastic syndromes and cancer.2,3,4 2’,3’,5’-triacetyl-5-Azacytidine is a prodrug form of 5-azacytidine that may be rapidly absorbed orally without formation of major metabolites in the gastrointestinal tract. | [Synthesis]
The general procedure for the synthesis of (2R,3R,4R,5R)-2-(acetyloxymethyl)-5-(4-amino-2-oxo-1,3,5-triazin-1 (2H)-yl) tetrahydrofuran-3,4-diyl diacetate from N-(trimethylsilyl)-4-(trimethylsilyl)oxy)-1,3,5-triazin-2-amine and tetraacetyl ribose was performed in the following manner. Under nitrogen protection, methylsilylated 5-azacytosine (Example A-1) was dissolved in dichloromethane (1.5 L) and stirred at 25-30°C for 10 minutes to obtain a clarified solution. Subsequently, the solution was cooled to 0-5°C. At this temperature, 1,2,3,5-tetraethyl-O-acetyl-β-D-ribofuranose (255.5 g, 0.8029 mol) was added all at once and stirring was continued for 10 minutes to keep the solution clarified. Next, tin chloride (255.6 g, 0.9813 mol) was slowly added dropwise at less than 10 °C, and the temperature was controlled to prevent overheating during the dropwise process, and the dropwise time was about 1 hour. After the dropwise addition, the reaction mixture was continued to be stirred at 0-5 °C for 5 h, during which the progress of the reaction was monitored by HPLC. 5g of the reaction mixture was taken and neutralized with saturated aqueous NaHCO3 solution at 10°C and the dichloromethane layer was separated for IPC-HPLC analysis. When HPLC showed no more than 0.5% residue of 5-azacytidine, the reaction mixture was transferred to a 5L round bottom flask for post-treatment. During the post-treatment stage, dichloromethane (1.0 L) and sodium bicarbonate (800.0 g) were first added to the reaction mixture at below 10 °C, followed by the slow dropwise addition of cold water (1.0 L) over a period of 30 min, taking care to control the temperature. After the dropwise addition was completed, stirring was continued for 30 min and after the white solid (tin oxide) precipitated, the filter was passed through Hyflo filtration and the filter cake was washed with dichloromethane (0.5 L). The organic layer was separated and washed sequentially with water (0.75 L), 10% EDTA disodium salt solution (150.0 g salt, 2 x 750 mL) and water (1.0 L) at less than 10 °C. After the organic layer was dried with anhydrous sodium sulfate, the solvent was removed by distillation at 40-45°C under atmospheric pressure, and then dried at 40-45°C under vacuum at 10-15 mmHg to obtain a viscous foaming solid. To this residue, methanol (200.0 mL) was added and dissolved at 30-35 °C, followed by distillation to remove the solvent at 40-45 °C, 10-15 mmHg under vacuum and vacuum degassing for 30 min to finally obtain 2',3',5'-triacetyl-5-azacytidine as a white to off-white crystalline solid (315.0 g). After several experiments, the average yield of 2',3',5'-triacetyl-5-azacytidine was approximately 305.2 g, with an average purity of 83.7% and an average yield of 77.2% (based on HPLC purity calculations). In five experiments, the highest yield reached 81.5% and the highest HPLC purity was 87.8%. The yield can be effectively improved by optimizing the reaction conditions, especially the parameters of the coupling and deprotection steps, and by using inexpensive and readily available metal Lewis acids such as stannous chloride and ferric chloride. | [in vivo]
in cd-1 mice, oral administration of tac for five days per week for 2 weeks didn’t result in animal deaths and weight loss, but induced changes in hematological parameters, lymph nodes, bone marrow, and duodenal epithelium. tac inhibited global dna methylation in the spleen and gut. in an in vivo l1210 leukemia model, tac exhibited antineoplastic activity [1]. | [storage]
Store at -20°C | [References]
[1] ziemba a, ramirez m c, freeman b, et al. abstract# 3369: development of oral demethylating agents for the treatment of myelodysplastic syndrome[j]. 2009. [2] brueckner b, boy r g, siedlecki p, et al. epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human dna methyltransferases[j]. cancer research, 2005, 65(14): 6305-6311. |
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