Synthesis method of 5-fluorocytidine

A technology of flucytosine nucleoside and synthesis method, which is applied in fermentation and other directions, can solve the problems of high synthesis cost, long synthesis route, and low photoactivity, and achieve shortened synthesis steps, less side reactions, and good reaction selectivity Effect

Inactive Publication Date: 2007-12-19
DONGHUA UNIV
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Problems solved by technology

[0004] The technical problem to be solved by the present invention is to provide a synthetic method of 5-fluorocytosine nucleoside to solve the shortcomings of high synthetic cost, long synthetic route, low yield and low photoactivity in the prior art

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  • Synthesis method of 5-fluorocytidine
  • Synthesis method of 5-fluorocytidine

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Experimental program
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Effect test

Embodiment 1

[0018] Take unsaturated thymidine (D-D4T) 1112mg (50mmol), 5-fluorocytosine (5-FC) 124mg (100mmol), KH 2 PO 4 30mL of buffer solution (pH6.35), 4ml of self-made deoxyribose transferase solution in a 100ml Erlenmeyer flask, shake in a constant temperature water bath at 150r / min for 20-24h. The reaction was boiled in boiling water for 5 min to stop the reaction. The reaction solution was lyophilized, and the residue was extracted with 10 ml of methanol / dichloromethane, and the extract was developed by TLC to obtain 214.96 mg of the product, Y: 16.8%.

Embodiment 2

[0020] Take unsaturated thymidine (D-D4T) 1112mg (50mmol), 5-fluorocytosine (5-FC) 124mg (100mmol), KH 2 PO 4 30mL of buffer solution (pH6.35), 4ml of self-made deoxyribose transferase solution in a 100ml Erlenmeyer flask, shake in a constant temperature water bath at 150r / min for 20-24h. The reaction was boiled in boiling water for 5 min to stop the reaction. The reaction solution was lyophilized, the residue was extracted with 30 ml of methanol, and concentrated under reduced pressure to obtain a solid mixture. The solid mixture was subjected to silica gel chromatography (20% CH 3 OH / CH 2 Cl 2 , v / v) purification to obtain 227.5 mg of the product, Y: 24.6%.

Embodiment 3

[0022] Take unsaturated thymidine (D-D4T) 1112mg (50mmol), 5-fluorocytosine (5-FC) 124mg (100mmol), citric acid buffer 30mL (pH6.35), 4ml homemade deoxyribose transferase solution in a 100ml Erlenmeyer flask, shaken at 150r / min in a constant temperature water bath for 20-24h. The reaction was boiled in boiling water for 5 min to stop the reaction. The reaction solution was lyophilized, the residue was extracted with 30 ml of methanol, and concentrated under reduced pressure to obtain a solid mixture. The solid mixture was subjected to silica gel chromatography (20% CH 3 OH / CH 2 Cl 2 , v / v) purification to obtain 227.0 mg of the product, Y: 24.1%.

[0023] Qualitative analysis during the reaction was performed by TLC. Activated silica gel G plate was used as carrier, dichloromethane-methanol-water (8:2:0.25v / v) was used as developer, and ultraviolet color was developed. R of D-D4T, D-D4FC, 5-FC and thymine f The reference values ​​are 0.82, 0.61, 0.29 and 0.05 respective...

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Abstract

The present invention provides one kind of 5-fluorocytidine synthesizing process, which synthesizes 5-fluorocytidine with thymine and 5-fluorocytosine under the catalysis of deoxyribotransferase. The said process has no radical protection and deprotection operation, less synthesis steps, raised destination product yield and lowered synthesis cost and no organic solvent caused environment pollution.

Description

technical field [0001] The invention relates to a method for synthesizing 5-fluorocytosine nucleoside, in particular to an enzymatic synthesis method for 5-fluorocytosine nucleoside. Background technique [0002] β-D-2′,3′-dideoxydidehydro-5-fluorocytidine (D-D4FC) is the second generation of nucleoside analogs with no toxic side effects on human mitochondria (Schinazi, R.; Ma , L.; Shi, J.; Liotta, D.; Faraj, A.; Sommadossi, J.P. Abstract 557 / 41174, 12th world AIDS conf, Geneva, June 28-July 3, 1998.), is a highly effective HIV and HBV selective inhibitor that inhibits HIV and HBV replication in vitro and in vivo. It has been reported that it can inhibit HIV-1 type virus resistant to AZT, ddC, ddI, D4T and 3TC, and at the same time, it also has a strong inhibitory effect on HBV (Hammond, J.; Schinazi, R.; Schlueter-Wirtz , S.; Mellors, J. Abstract 597, 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31-fuebuary4, 1999.). Due to its good phar...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12P19/32
Inventor 朱利民傅绍军
Owner DONGHUA UNIV
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