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Method for synthesizing acyclovir and ganciclovir by carbon-hydrogen bond activation

A technology of carbon-hydrogen bond activity and ganciclovir, which is applied in the field of synthesis of raw materials, can solve the problems of long side chain synthesis route and low total yield, and achieve the effect of cheap raw materials, short reaction route and easy availability of raw materials

Inactive Publication Date: 2018-11-30
XINYANG NORMAL UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The traditional synthetic methods of acyclovir and ganciclovir mainly rely on the condensation reaction catalyzed by Lewis acid or protonic acid as the key step, and the side chain synthesis routes of acyclovir and ganciclovir are relatively long, and the total yield The rate is low (H.Gao, A.K.Mitra, Syn.Commun., 2001, 31, 1399-1419; Wang Jiesheng, Ji Xiuzhen, Zhu Qichang, etc. Chinese Journal of Pharmaceutical Industry, 1992, 23, 289; M.Qian, R.Glaser, J. Am. Chem. Soc., 2004, 126, 2274-2275)

Method used

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  • Method for synthesizing acyclovir and ganciclovir by carbon-hydrogen bond activation
  • Method for synthesizing acyclovir and ganciclovir by carbon-hydrogen bond activation
  • Method for synthesizing acyclovir and ganciclovir by carbon-hydrogen bond activation

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Experimental program
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Effect test

Embodiment 1

[0021] In the first step, the reaction formula is as follows:

[0022]

[0023] 5 mmoles of N2-acetylguanine (1) were dissolved in 15 mL of anhydrous DMF, 10 mmoles of potassium carbonate and 6 mmoles of methyl iodide were added, and the reaction was stirred at room temperature for 8 hours, and then 30 mL of ethyl acetate was added to fully Stir, transfer to a separatory funnel, wash twice with water and once with saturated brine to collect the organic phase, dry with anhydrous sodium sulfate, remove the solvent under reduced pressure, and purify the residue by silica gel column chromatography to obtain light yellow syrupy N9 -Methyl-N2-acetyl protected guanine (2), the product yield is 78%.

[0024] In the second step, the reaction formula is as follows:

[0025]

[0026] 5 mmoles of N9-methyl-N2-acetylguanine (2) were dissolved in 20mL of anhydrous toluene, 0.5 mmoles of palladium acetate were added, 6 mmoles of PhI(OPiv)2 and 6 mmoles of monoacetyl protected Ethylene glycol (HOC...

Embodiment 2

[0033] In the first step, the reaction formula is as follows:

[0034]

[0035] 5 mmoles of N2-acetylguanine (1) were dissolved in 15 mL of anhydrous DMF, 10 mmoles of potassium carbonate and 6 mmoles of methyl iodide were added, and the reaction was stirred at room temperature for 8 hours, and then 30 mL of ethyl acetate was added to fully Stir, transfer to a separatory funnel, wash twice with water and once with saturated brine to collect the organic phase, dry with anhydrous sodium sulfate, remove the solvent under reduced pressure, and purify the residue by silica gel column chromatography to obtain light yellow syrupy N9 -Methyl-N2-acetyl-protected guanine (2), the product yield is 78%.

[0036] In the second step, the reaction formula is as follows:

[0037]

[0038] 5 mmoles of N9-methyl-N2-acetylguanine (2) are dissolved in 20mL of anhydrous toluene, 0.5 mmoles of palladium acetate are added, 6 mmoles of PhI(OPiv)2 and 6 mmoles of 1,3-acetyl are added Glycerol, the temperat...

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Abstract

The invention discloses a method for synthesizing acyclovir and ganciclovir by carbon-hydrogen bond activation and belongs to the field of organic synthesis. The method comprises that inexpensive guanine as a raw material undergoes methyl protection on 9th NH, a high-valent iodine reagent and monoacetyl-protected ethylene glycol or 1, 2-isopropylidene-protected glycerol are added into the raw material under catalysis of palladium acetate, the mixture undergo a heating reaction to produce acetyl-protected acyclovir or acetyl-protected ganciclovir, and the acetyl group is removed by an inorganicalkali alcohol solution so that acyclovir and ganciclovir are obtained. The method utilizes cheap and easily available raw materials, prevents use risk and corrosive reagents, has the advantages of short reaction route, simple operation, high atomic economy and high total product yield, provides a novel synthesis route of acyclovir and ganciclovir and has a potential application prospect.

Description

Technical field [0001] The invention relates to a method for synthesizing raw materials, in particular to a method for synthesizing acyclovir and ganciclovir by using carbon-hydrogen bond activation, and belongs to the technical field of organic chemistry. Background technique [0002] Acyclovir is a synthetic non-cyclic purine nucleoside analogue. Acyclovir is mainly used for various infections caused by herpes simplex virus. It can be used for initial or recurrent skin, mucous membrane, external genital infections and immunity HSV infections in patients with defects are the first choice for the treatment of HSV encephalitis, and there is a huge demand at home and abroad. Ganciclovir was developed by Syntex in the United States. Its structure is similar to acyclovir. It has a stronger and broader-spectrum antiviral effect than acyclovir, and is especially suitable for the treatment of ocular CMV infection. [0003] The traditional synthetic methods of acyclovir and ganciclovir ma...

Claims

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Application Information

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IPC IPC(8): C07D473/18
CPCC07D473/18
Inventor 饶伟浩蒋莉莉刘晓梦陈眉君江欣
Owner XINYANG NORMAL UNIVERSITY
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