9-(2-羟基乙基)-6-氨基-2-烷硫基嘌呤衍生物的合成

Synthesis of 2-alkylthio-6-amino-9-(2-hydroxylethyl)purines

摘要:

以2-氨基-6-氯嘌呤为原料，与2-溴乙基乙酸酯反应得到9-乙酰氧基乙基-2-氨基-6-氯嘌呤(Ⅰ)，收率65.6%；Ⅰ经重氮-烷硫化得到9-乙酰氧基乙基-2-烷硫基-6-氯嘌呤(Ⅱ)，收率58.3~72.1%；Ⅱ与叠氮化钠反应得到9-乙酰氧基乙基-2-烷硫基-6-叠氮嘌呤(Ⅲ)，收率86.4~92.0%。经核磁检测Ⅲ在溶液中存在叠氮结构(A)和四氮唑结构(T)的互变异构现象，CDCl3中叠氮结构比例在61.5~67.2%。采用PPh3-HCl-DMSO为反应体系，“一锅法”将叠氮基还原为氨基同时将酯基彻底水解，高收率 (~90%)得到9-(2-羟基乙基)-6-氨基-2-烷硫基嘌呤衍生物Ⅳ。这些化合物的结构经IR，1H NMR，13C NMR及HRMS 得到确证。

Abstract:

2-Amino-6-chloropurine as the starting material was treated with 2-bromoethyl acetate to product 9-acetoxyethyl-2-amino-6-chloropurine (Ⅰ, 65.6% yield). Compound Ⅰwas diazotized and reacted with disulfides to afford 9-acetoxyethyl-2-alkythio-6-chloropurine (Ⅱ, 58.3-72.1% yield). NaN3 was reacted with Ⅱto acquire 9-acetoxyethyl-2-alkythio-6-triazo purine (Ⅲ, 86.4-92.0% yield). The result of NMR test (Ⅲ)showed that there were azido tautomer(A)and tetrazolyl tautomer(T) in the solution, and the ratio of azido tautomer was 61.5-67.2%. We use PPh3-HCl-DMSO as the reaction solvent to reduced trizao to amino and hydrolyzed the ester completely to afford the 2-alkylthio-6-amino-9- (2-hydroxylethyl)purines (Ⅳ) in the good yield（~90%） in one pot. All the compounds synthesized were comfirmed through IR, 1H NMR, 13C NMR, and HRMS.