22432-95-7

Basic information

• Product Name: α-Decitabine
• Synonyms: s-Triazin-2(1H)-one,4-amino-1-(2-deoxy-a-D-erythro-pentofuranosyl)- (8CI); 1-(2-Deoxy-a-D-ribofuranosyl)-5-azacytosine; NSC 127717; a-Decitabine
• CAS NO: 22432-95-7
• Molecular Formula: C₈H₁₂N₄O₄
• Molecular Weight: 228.20528
• Product Categories: Heterocycles, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 22432-95-7.mol

Chemical Properties

• Boiling Point: 485.8°Cat760mmHg
• Flash Point: 247.6°C
• Appearance: /
• Density: 1.9g/cm³
• Storage Temp.: -20°C Freezer
• Solubility: Methanol (Slightly, Heated), Water
• PKA: 14.02±0.60(Predicted)
• CAS DataBase Reference: α-Decitabine(CAS DataBase Reference)
• NIST Chemistry Reference: α-Decitabine(22432-95-7)
• EPA Substance Registry System: α-Decitabine(22432-95-7)

Safety Data

• Hazardous Substances Data: 22432-95-7(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
α-Decitabine is used as an anticancer agent for its ability to inhibit DNA methylation, which results in the reactivation of silenced tumor suppressor genes and the induction of apoptosis in cancer cells. This makes it a valuable therapeutic option for the treatment of various types of cancer, including myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and other solid tumors.
Used in Epigenetic Therapy:
α-Decitabine is used as an epigenetic therapy agent to modulate gene expression and reverse the abnormal methylation patterns observed in cancer cells. By targeting DNA methyltransferase enzymes, it can restore normal cellular function and potentially prevent the development and progression of cancer.
Used in Drug Development:
α-Decitabine serves as a key compound in the development of new drugs and therapies targeting epigenetic mechanisms in cancer. Its unique properties and mechanism of action make it an attractive candidate for combination therapies and the development of novel agents with improved efficacy and reduced toxicity.

Upstream product

• 69304-64-9 N-(formylamidino)-N'-β-D-2-deoxyribofuranosylurea 
• 931-86-2 5-azacytosine 
• 21740-23-8 3,5-O-bis(4-chlorobenzoyl)-2-deoxy-α-D-ribofuranosyl chloride 
• 1034301-08-0 1-(3,5-di-O-p-chlorobenzoyl-2-deoxy-β-D-ribofuranosyl)-5-azacytosine 
• 1207459-15-1 1-O-acetyl-3,5-di-O-(4-chlorobenzoyl)-2-deoxy-D-ribofuranose 
• 52523-35-0 2-(trimethylsilylamino)-4-(trimethylsilyloxy)-s-triazine 
• 951-78-0 2'-deoxyuridine 
• 80184-05-0 1-chloro-2-deoxy-D-ribofuranose 
• 17039-17-7 2-deoxy–α-D-ribose 1-phosphate 
• 51255-17-5 1-O-methyl-2-deoxy-D-ribofuranoside 
• 2353-33-5 5-aza-2'-deoxycytidine 
• 3601-89-6 Hoffer's chlorosugar 
• 22432-93-5 3',5'-O-acetyl-2'-deoxy-5-azacytidine 
• 1140891-02-6 4-amino-1-[3,5-di-O-(p-chlorobenzoyl)]-2-deoxy-alpha-D-ribofuranosyl-1,3,5-triazin-2(1H)-one 

Downstream Products

• 931-86-2 5-azacytosine 
• 452-51-7 D-2-deoxyribose 
• 1423539-59-6 C₂₁H₂₇N₅O₇ 
• 1423539-61-0 C₂₁H₂₇N₅O₇ 
• 1423539-65-4 C₂₅H₂₇N₅O₇ 
• 1423539-63-2 C₂₂H₂₉N₅O₇ 
• 107036-47-5 5'-O-(4,4'-dimethoxytrityl)-2'-deoxy-5-azacytidine 
• 2353-33-5 5-aza-2'-deoxycytidine 
• 929904-85-8 guadecitabine sodium salt 
• 929904-84-7 guadecitabine triethylammonium salt 
• 117436-81-4 C₅₆H₆₉N₆O₁₉P 
• 117399-77-6 5,6-dihydro-5-azacytidine phosphoramidite 
• 117436-80-3 Isobutyric acid 3-{(2R,4S,5R)-5-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-8-isobutyryl-7-isobutyryloxy-2-oxo-2,3,4,6,7,8-hexahydro-imidazo[1,2-a][1,3,5]triazin-6-yl ester 
• 431890-08-3 (5-{(2R,4S,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-4-oxo-4,5-dihydro-[1,3,5]triazin-2-yl)-carbamic acid 2-(4-nitro-phenyl)-ethyl ester 

Relevant articles and documents

Development of an immobilized biocatalyst based on Bacillus psychrosaccharolyticus NDT for the preparative synthesis of trifluridine and decytabine

The immobilization of Bacillus psychrosaccharolyticus nucleoside 2′-deoxyribosyltransferase was deeply investigated and finally optimized. The best immobilization procedure resulted to be ionic adsorption on PEI 600 Da agarose followed by crosslinking with 70% oxidized dextran (20 kDa). The percentage of recovered activity was further improved (from 21% to 33%) by the addition of 20% glycerol to the immobilization mixture. The resulting biocatalyst showed a stability profile similar to that of the soluble enzyme and it was used for the preparative synthesis of trifluridine and decytabine obtaining conversions ranging from 50% to 76%.

Decitabine intermediate compound VI

The invention belongs to the technical field of chemical synthesis, and provides a decitabine intermediate compound. A preparation route of the decitabine intermediate compound comprises the followingsteps: taking an oxymethyl compound of a hydroxyl group at a 1 site of 2-deoxy-D-ribose as a raw material, protecting a hydroxyl group at a 3 site and a hydroxyl group at a 5 site respectively, then performing acetylation substitution on a 1 site of sugar, and further treating to obtain the compound. The method is simple and convenient to operate, does not need special equipment, is good in product purity and high in yield, and is suitable for industrial production; decitabine is further synthesized by utilizing the compound, so that the stereoselectivity is high, and the purity isgood.

Decitabine intermediate compound V

The invention belongs to the technical field of chemical synthesis, and provides a decitabine intermediate compound. A preparation route of the decitabine intermediate compound comprises the followingsteps: taking an oxymethyl compound of 2-deoxy-D-ribose 1 site hydroxyl as a raw material, respectively protecting 3 site and 5 site hydroxyl, and further treating to obtain the compound provided by the invention. The method is simple and convenient to operate, does not need special equipment, and is good in product purity, high in yield and suitable for industrial production; and decitabine is further synthesized by utilizing the compound, so that the compound is high in stereoselectivity and good in purity.

Preparation method of decitabine

The invention belongs to the technical field of organic synthesis, and provides a preparation method of decitabine. The preparation method specifically comprises the following steps: first carrying out reflux extraction to obtain a mixture of decitabine alpha and beta isomers, and then separating the isomers by applying the supercritical fluid technology to obtain high-purity decitabine. Comparedwith the prior art, the technical method which is simple in operation process, high in separation efficiency, high in product yield, high in final product purity and suitable for industrial productionis provided.

2-deoxy-D-ribose derivative

The invention belongs to the field of medicine synthesis, and provides a 2-deoxy-D-ribose derivative (III). When the derivative (III) is used for preparing decitabine, the stereoselectivity is good, and the yield is high. The invention provides a preparation method of the derivative. The preparation method comprises the following steps: step a, carrying out oxygen methylation on 1-position hydroxyl of 2-deoxy-D-ribose; and step b, protecting hydroxyl groups at positions 3 and 5, and further carrying out sulfonation on 1-position oxymethyl. The method is simple and convenient to operate, free of special equipment, good in product purity, high in yield and suitable for industrial production.

Synthetic method of decitabine

The present invention relates to a synthetic method of decitabine, and discloses a method for synthesizing a compound as shown in a formula I, The method comprises the steps of: reacting a compound IIwith a compound III by a following reaction in a solvent under the action of TMSOTf to obtain a compound I. The synthetic method of the invention has the advantages that the raw materials are easy toobtain, the operation is safe, the conditions are mild and easy to control, and a solid product obtained by an acylation protection is easy to be crystallized and purified, which is favorable for thenext reaction and improves the selectivity of a final beta-isomer product, no further conversion to hydroxymethyl is required, the reaction step is simplified, the reaction yield of each step is good, the atomic economy is high, and the method is suitable for a large number of industrial production and the like.

Preparation method of beta-nucleoside compound

The invention provides a method for preparing beta-nucleoside or analogue thereof, comprising the following steps: 1) enabling nitrogenous base or analogue thereof to generate silylanizing reaction under the existence of trimethylsilyl trifluoromethanesulfonate (TMSOTf), to obtain the nitrogenous base or analogue thereof protected by trimethylsilyl; 2) enabling a reaction liquid to directly perform glycosylation reaction with quintuple cyclose or hexahydric cyclose sealed by a hydroxy protection group, so as to obtain a sealed beta-nucleoside or analogue thereof; 3) performing protection groupremoval reaction, to obtain the beta-nucleoside or analogue thereof. The method disclosed by the invention is simple in operation, energy-saving and environment-friendly, a key intermediate of the beta-nucleoside or analogue thereof is prepared by a one-pot methoid, and the yield of beta configuration substance is remarkably increased, and the preparation method is suitable for industrial application.

A used with the industrial production method for the synthesis of

The invention relates to a decitabine synthesis and industrial production method, which comprises the following steps of: using 2-Deoxy-D-ribose as a raw material, performing a reaction between the raw material and methanol to obtain glucoside, protecting 3,5-dihydroxy by the use of 9-fluorenylmethyloxycarbonyl, reacting with hydrogen chloride to obtain 1-chlorflurecol sugar, performing a reaction between 1-chlorflurecol sugar and silanized 5-azacytosine, carrying out deprotection, and refining to obtain decitabine. The invention is characterized in that stannic chloride is not required during the condensation reaction between 1-chlorflurecol sugar and silanized 5-azacytosine so as to avoid the problem of excessive contents of heavy metals in pharmaceutical materials; and simultaneously the amount of trimethylsilyl trifluoromethanesulfonate and reaction conditions are controlled so as to increase the body burden of beta in the product.

Enzymatic synthesis and phosphorolysis of 4(2)-thioxo- and 6(5)-azapyrimidine nucleosides by E. coli nucleoside phosphorylases

The trans-2-deoxyribosylation of 4-thiouracil (4SUra) and 2-thiouracil (2SUra), as well as 6-azauracil, 6-azathymine and 6-aza-2-thiothymine was studied using dG and E. coli purine nucleoside phosphorylase (PNP) for the in situ generation of 2-deoxy-α-D-ribofuranose-1-phosphate (dRib-1P) followed by its coupling with the bases catalyzed by either E. coli thymidine (TP) or uridine (UP) phosphorylases. 4SUra revealed satisfactory substrate activity for UP and, unexpectedly, complete inertness for TP; no formation of 2′-deoxy-2-thiouridine (2SUd) was observed under analogous reaction conditions in the presence of UP and TP. On the contrary, 2SU, 2SUd, 4STd and 2STd are good substrates for both UP and TP; moreover, 2SU, 4STd and 2′-deoxy-5-azacytidine (Decitabine) are substrates for PNP and the phosphorolysis of the latter is reversible. Condensation of 2SUra and 5-azacytosine with dRib-1P (Ba salt) catalyzed by the accordant UP and PNP in Tris·HCl buffer gave 2SUd and 2′-deoxy-5-azacytidine in 27% and 15% yields, respectively. 6-Azauracil and 6-azathymine showed good substrate properties for both TP and UP, whereas only TP recognizes 2-thio-6-azathymine as a substrate. 5-Phenyl and 5-tert-butyl derivatives of 6-azauracil and its 2-thioxo derivative were tested as substrates for UP and TP, and only 5-phenyl- and 5-tert-butyl-6-azauracils displayed very low substrate activity. The role of structural peculiarities and electronic properties in the substrate recognition by E. coli nucleoside phosphorylases is discussed.

Synthesis method of decitabine for treating primary or secondary leukemia

The invention discloses a synthesis method of decitabine for treating primary or secondary leukemia. The method comprises the following steps: 1) adding 1-chloro-2-deoxy-D-ribofuranose, cobalt nitrate and (R)-1,1'-linked-2-naphthol in DMF, stirring and mixing for 1-2 hours at 45-60 DEG C, then cooling to room temperature, and filtering to obtain mixture M containing 1-chloro-2-deoxy-D-ribofuranose complex; and 2) in the presence of triethylamine, adding 2,4-bis-trimethylsilyl-S-triazine in the mixture M obtained in the step 1), stirring for reacting for 6-8 hours at 30-40 DEG C, soaking in water, extracting with dichloromethane, washing with dilute hydrochloric acid, washing with saturated sodium bicarbonate, concentrating, and carrying out ethanol recrystallization to obtain decitabine. The method for preparing decitabine effectively improves the selectivity of a beta product and the yield of decitabine, thereby providing a new way for preparing decitabine.