A kind of method utilizing carbon-hydrogen bond activation to synthesize acyclovir and ganciclovir

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 low total yield and long side chain synthesis route, and achieve short reaction route, cheap raw materials and high atom economy. Effect

Inactive Publication Date: 2020-01-07
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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  • A kind of method utilizing carbon-hydrogen bond activation to synthesize acyclovir and ganciclovir
  • A kind of method utilizing carbon-hydrogen bond activation to synthesize acyclovir and ganciclovir
  • A kind of method utilizing carbon-hydrogen bond activation to synthesize acyclovir and ganciclovir

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Experimental program
Comparison scheme
Effect test

Embodiment 1

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

[0022]

[0023] 5 mmol of N2-acetylguanine (1) was dissolved in 15 mL of anhydrous DMF, 10 mmol of potassium carbonate and 6 mmol of methyl iodide were added, stirred and reacted at room temperature for 8 hours, then 30 mL of ethyl acetate was added, fully Stir, transfer to a separatory funnel, wash twice with water, once with saturated brine, collect the organic phase, dry over 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 was 78%.

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

[0025]

[0026] 5 mmol of N9-methyl-N2-acetylguanine (2) was dissolved in 20 mL of anhydrous toluene, 0.5 mmol of palladium acetate was added, 6 mmol of PhI(OPiv)2 and 6 mmol of monoacetyl-protected Ethylene glycol (HOCH2CH2OAc), the tempera...

Embodiment 2

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

[0034]

[0035] 5 mmol of N2-acetylguanine (1) was dissolved in 15 mL of anhydrous DMF, 10 mmol of potassium carbonate and 6 mmol of methyl iodide were added, stirred and reacted at room temperature for 8 hours, then 30 mL of ethyl acetate was added, fully Stir, transfer to a separatory funnel, wash twice with water, once with saturated brine, collect the organic phase, dry over 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 was 78%.

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

[0037]

[0038] 5 mmol of N9-methyl-N2-acetylguanine (2) was dissolved in 20 mL of anhydrous toluene, 0.5 mmol of palladium acetate was added, 6 mmol of PhI(OPiv)2 and 6 mmol of 1,3-acetyl Glycerol, the temperature rose to 120 degrees Celsiu...

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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 synthesis method of raw materials, in particular to a method for synthesizing acyclovir and ganciclovir by utilizing carbon-hydrogen bond activation, and belongs to the technical field of organic chemistry. Background technique [0002] Acyclovir is a synthetic non-cyclic purine nucleoside analog. 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 infection and immune The HSV infection that occurs in the defective person is the drug of choice for the treatment of HSV encephalitis, and there is a huge demand at home and abroad. Ganciclovir was developed by Syntex Corporation of the United States. Its structure is similar to that of acyclovir. Compared with acyclovir alone, it has a stronger and broader antiviral effect, and is especially suitable for the treatment of ocular CMV virus infection. [0003] The traditional...

Claims

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Application Information

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Patent Type & Authority Patents(China)
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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