泛昔洛韦的合成

Synthesis of Famciclovir

以2-氨基-6-氯嘌呤(2)为原料,在相转移催化剂四丁基溴化铵催化下与3-溴丙烷-1,1,1-三甲酸乙酯(3)缩合,得2-氨基-6-氯-9-(2,2-二乙氧羰基丁酸乙酯-4-基)嘌呤(4)。4用乙醇钠溶液脱羧得2-氨基-6-氯-9-(2-乙氧羰基丁酸乙酯-4-基)嘌呤(5)。5在AlCl3催化下,用NaBH4作还原剂还原得2-氨基-6-氯-9-(4-羟基-3-羟甲基丁基)嘌呤(6)。6在4-二甲基氨基吡啶(DMAP)催化下,与醋酐反应得2-氨基-6-氯-9-(4-乙酰氧基-3-乙酰氧基甲基丁基)嘌呤(7)。7在Pd-C催化下,氢化脱氯得泛昔洛韦(1)。以2-氨基-6-氯嘌呤(2)计总收率为55%。

Famciclovir （1） was synthesized from 2-amino-6-chloropurine（2） as the starting material.2 reacted with 3-bromo-propane-1, 1,1-tricarboxylate triethyl ester（3） with phase-transfer catalyst to obtain 2-amino-6-chloro-9-（ ethyl 2,2-dicaroethoxybu-tanoate-4-yl） purine （4）. 4 decarboxylated with sodium ethoxide gave 2-amino-6-chloro-9-（ ethyl 2-carboethoxybutanoate-4-yl） purine（5）. 5 was reduced afterwards to 2-amino-6-chloro-9-（4-hydroxy-3-hydroxymethylbut-l-yl） purine（6） with NaBH4 in AlCl3 as catalyst.6 reacted with Ao2O to give 9-（4-acetoxy-3-acetoxymethylbut-1-yl）-2-amino-6-chloropurine（7）, followed by reduction with hydrogen to give 1. The overall yield calctdated based oil 2-amino-6-chloropurine was 55%.