阿昔洛韦的合成工艺改进

Improvement on the Synthesis Process of Acyclovir

设计了1条以NaHSO4为催化剂合成阿昔洛韦的新工艺,以醋酐和1,3-二氧戊环为起始原料,合成2-氧杂-1,4-丁二醇二乙酯,然后再与乙酰化后的鸟嘌呤发生缩合制得双乙酰阿昔洛韦,双乙酰阿昔洛韦在Na2CO3水溶液中水解得到目标产物阿昔洛韦。考察了该工艺中反应温度、催化剂用量、溶剂等对反应收率和产品质量的影响。结果表明,在合成关键中间体2-氧杂-1,4-丁二醇二乙酯中,反应温度宜选用60℃;合成双乙酰鸟嘌呤时n(鸟嘌呤):n(cat)=1.0:0.1为较佳;合成双乙酰阿昔洛韦时选用甲苯作为反应的较佳溶剂。总收率达到79%,并且产物纯度较高,适合工业化生产。

A new process for the preparation of acyclovir which takes NaHSO4 as catalyst was designed.First 2-oxa-1,4-butanediol diacetate was synthesized from acetic anhydride and 1,3-dioxycyclopentane,followed by condensation with acetyl guanine to get diacetylacylovir.Acyclovir was obtained from diacetylacylovir by hydrolyzed in the presence of Na2CO3.The effects of catalyst dosage,reaction temperature and solvent on the yields and product quality were discussed.The better temperature of synthesis 2-oxa-1,4-butanediol diacetate was 60 ℃ and the better mass ratio of n(guanine):n(cat)=1.0:0.1 in the preparation of acetyl guanine.In thepreparation of diacetylacylovir the better solvent was toluene.The overall yield of this process was up to 79% and the products had high purity which fit for large production.