2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤的合成

报道了2-氨基-6-氟-9-(4-羟基-3-羟甲基丁基)嘌呤(1)的合成, 通过对起始原料2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧甲基丁基)嘌呤(2)水解脱去乙酰基, 得到2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤(3). 化合物3与三甲胺乙醇溶液在混合溶剂[V(THF)∶V(DMF)＝3∶1]中反应得到相应的氯化铵盐4, 然后与KF在DMF溶剂中反应, 得到化合物1. 产品经UV-vis, IR, ¹H NMR, ¹⁹F NMR和MS表征. 考察了反应温度、氟化试剂等因素对氟化反应的影响, 为6位含氟的嘌呤核苷类化合物的合成提供了一种直接、简易的新方法.

Synthesis of 2-Amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbutyl)- purine

The fluorinated nucleoside analogue 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbutyl)purine (1) is a potential antiviral agent and ¹⁸F-radiopharmaceutical reference compound. Its synthesis was described. 2-Amino-6-chloro-9-(4-acetoxy-3-acetoxymethylbutyl)purine (2) was hydrolyzed to 2-amino-6-chloro-9-(4- hydroxy-3-hydroxymethylbutyl)purine (3) by using potassium carbonate in a mixed solution of water and methanol at 0 ℃, then was converted to the corresponding trimethylammonium chloride (4) by treatment with trimethylamine (TMA) in ethanolic solution in a mild condition. Com-pound 4 was reacted with anhydrous KF in DMF to produce 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxymethylbutyl)purine (1) in 87.3% yield. The structures of the products were characterized by UV-vis, IR, NMR and MS spectra. Some factors affecting the yield of fluorina-tion reaction were investigated.