Novel 2'-uridine azide and synthetic method thereof

A technology for uridine nucleoside and synthesis method, which is applied in the field of novel 2'-azidouridine nucleoside and its synthesis, can solve the problems of short half-life, high toxicity, limited clinical application and the like, and achieves simple post-processing and reaction conditions. Gentle, easy-to-use effect

Inactive Publication Date: 2018-10-26
南京百芙利科技有限责任公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the general toxicity of nucleoside drugs, the short half-life in the body, and the disadva...

Method used

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  • Novel 2'-uridine azide and synthetic method thereof
  • Novel 2'-uridine azide and synthetic method thereof
  • Novel 2'-uridine azide and synthetic method thereof

Examples

Experimental program
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Embodiment 1

[0029] Synthesis of 3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane)uridine:

[0030]

[0031] In a 100ml two-necked bottle, add 40ml pyridine and 2.4g (10mmol) uridine respectively, and under nitrogen protection conditions, add dropwise 3.2g (10mmol) 1,3 dichloro-1,1,3,3-tetraisopropyl disiloxane, then stirred at room temperature for 2 days. After the completion of the reaction detected by TLC, spin dry to remove pyridine, add 50ml of dichloromethane, wash with water three times (30ml x 3), dry with anhydrous magnesium sulfate, spin dry the solvent, load the sample by dry method, and separate by column chromatography (dichloromethane) Methane / methanol=20:1). 4.4 g of 3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane)uridine was obtained with a yield of 90%.

Embodiment 2

[0033] Synthesis of 3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane)-2'-oxouridine:

[0034]

[0035] In a 250ml two-necked flask, add 60ml of dichloromethane, 4.5ml of pyridine, 2.7ml of acetic anhydride and 2.7g (27mmol) of chromium trioxide, slowly drop 4.9g (10mmol) of 3',5'-O-(1, 1,3,3-Tetraisopropyl-1,3-disiloxane)uridine (dissolved in 30ml of dichloromethane), then stirred at room temperature for 30 minutes, after the TLC plate detected that the reaction was complete, add 400ml of dichloro Methane, then use a sand core funnel (add 2ml thick silica gel layer) to filter, wash the silica gel layer and precipitate with 200ml dichloromethane, combine the organic phases, wash with water three times (150ml x 3), and dry with anhydrous magnesium sulfate , and the solvent was spin-dried to obtain 4.5 g 3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane)-2'-oxouridine, yield 93%.

Embodiment 3

[0037] Synthesis of 3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane)-2'-deoxy-2'-methyleneuridine:

[0038]

[0039]In a 100ml two-necked flask, under nitrogen protection, 45ml dimethyl sulfoxide and 1.4g 60% NaH (35mmol) were added respectively, and then heated to 65°C until the sodium hydrogen was completely dissolved. Then cool to room temperature, add 14.3g (40mmol) methyl triphenylphosphine bromide, continue stirring for 45 minutes, add 4.8g (10mmol) 3',5'-O-(1,1,3,3-tetra isopropyl-1,3-disiloxane)-2'-oxouridine, and react at 50 °C for 1 hour. Spin to dry the solvent, add 200ml of water, adjust the pH to 7 with glacial acetic acid, extract the aqueous phase three times with dichloromethane (100ml x 3), dry with anhydrous magnesium sulfate, spin to dry the solvent, dry load, and column chromatography Separation (dichloromethane / methanol=8:1). 3.2 g of 3',5'-O-(1,1,3,3-tetraisopropyl-1,3-disiloxane)-2'-deoxy-2'-methyleneuridine were obtained, yielding rate of 67%.

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Abstract

The invention discloses novel 2'-uridine azide and a synthetic method thereof. The structural formula of the compound is as shown in specification, and reaction steps of the synthetic method of the novel 2'-uridine azide are as shown in specification. The synthetic method is mild in reaction condition, simple in aftertreatment and simple and convenient to operate, and conditions are provided for synthesis of the compound on a large scale. The obtained compound can serve as an active ingredient of an antiviral drug, and has potential application prospect in development of a new antiviral nucleosides drug. The novel 2'-uridine azide lays a foundation for further discovery of the new antiviral nucleosides drug, and meanwhile, the nucleoside analog of a novel 2' modifying structure also provides a new though for nucleoside modification in the future.

Description

technical field [0001] The invention belongs to the technical field of chemical synthesis of nucleosides, and in particular relates to a novel 2'-azidouridine nucleoside and a synthesis method thereof. Background technique [0002] Nucleosides have been a major research direction in the fields of bioorganic and medicinal chemistry. As the structural unit of nucleic acid, nucleoside is involved in the retention, replication and transcription of genetic information, so it plays a very important role in all life systems. [0003] Viral infections are rampant all over the world. According to incomplete statistics, among human infectious diseases, viral infections are as high as 60%-65%, far exceeding bacterial infections (15%). It can cause AIDS, various types of hepatitis and herpes viruses Infection and other diseases seriously endanger human health and life. Therefore, as a global public health problem, it is particularly important to develop and develop new antiviral drugs...

Claims

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Application Information

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IPC IPC(8): C07H19/06C07H1/00A61K31/7072A61P31/12
CPCC07H19/06A61P31/12C07H1/00
Inventor 高元和卢金宁
Owner 南京百芙利科技有限责任公司
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