[Synthesis of 5-fluorouracil derivatives containing alkanoic acid]
Liu-hua Xu1, Ling-ling Weng, Hu Zheng
1Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
Objective:
To synthesize 5-fluorouracil derivatives containing 2-5 carbon alkanoic acid.
Methods:
N1-substituted derivatives containing alkanoic acid were prepared through the hydrolysis of these products of the reaction of haloesters and excessive amount of 5-fluorouracil. 5-fluorouracil were protected with tertbutoxycarbonyl (Boc) at N1-position, then reacted with haloesters and deprotected in turn, through this "one-pot" method, N3-substituted 5-FU alkanoic acid esters can be obtained, with high yields (75%-85%). The hydrolysis of these products gave N3-substituted 5-FU alkanoic acid at last.
Results:
Including 10 new compounds and 8 aim compounds, 16 derivatives of 5-fluorouracil were obtained and confirmed by the spectral detection.
Conclusions:
The reaction of excessive amount of 5-fluorouracil and haloesters can produce a good yield of N1-substituted derivatives. N3-substituted derivatives can be obtained through the reactions of 5-fluorouracil protected with Boc at N1-position and haloesters.
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