氟嘧啶二酮（抗代謝抗癌藥）之合成法研討

Abstract

氟嘧啶二酮（5-Fluorouracil）為目前國內外已在臨床使用的抗代謝性抗癌藥。本研究之目的在收集以往有關該藥物之合成文獻及專利加以探討，選擇最可行及最經濟的合成途徑以訓練自製力，並期改良以提高產率。本研究經選擇決定採用改良之Duschinsky專立法及kaes專利法合成氟嘧啶二酮。（一）Duschinsky專立法乃利用氟乙酸乙酯與甲酸乙酯為出發物與烷基硫?行脫水反應，文獻值產率為17.3％，但追試值為0％，即得不到產物，經改良方法後可得產率22.7％。（二）Kaes專立法乃以氟乙酸乙酯與甲酸甲酯為出發物與氨基甲鹽酸鹽行脫水反應。實驗結果知本專立法之可行性高，其追試值為28.3％（文獻值28～33％）

5-Fluorouracil is one of the anticancer drugs in clinical use. After checking the documentation about synthetic methods and patents, we found two improved methods to be valid and economical. The synthetic methods are (1) Duschinsky method : To the potassium ethoxide in ether solution were added ethyl-fluoro-acetate and ethyl formate. The reaction mixture was allowed to react wity alkyl-thiourea salt to form 5-fluorouracil. After repetition of this method no product was obtained though 17.3% yield was reported. The improved method was to proceed the reaction in sodium methoxide toluene solution instead of ether solution, and it gave the tatal yield up to 22.7% (2) Kaes method: To the sodium methoxide in toluene solution were addid ethylfluoroacetate and methylformate. The reaction mixture was allowed to dehydrate with Guanidine to give 5-fluorouracil, with a total yield of 28.3% (doc. 28 -33%).