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9-[(2,3-二羟基-1-丙氧基)甲基]鸟嘌呤是欧洲药典8.0版本中所收载的抗病毒药物更昔洛韦(Ganciclovir)的一个有关物质(也称为杂质)。本文以苄基缩水甘油醚为原料,依次通过酸催化的环氧开环反应、伯羟基选择性保护、仲羟基苄醚化反应、伯羟基去保护、氯甲基醚化和取代反应制备得到侧链2,3-二苄氧基-1-乙酰氧基甲氧基丙烷。2,3-二苄氧基-1-乙酰氧基甲氧基丙烷接着和N2,9-二乙酰基鸟嘌呤发生缩合反应随后经过氢解脱苄基保护和碱性水解最终合成得到目标产物9-[(2,3-二羟基-1-丙氧基)甲基]鸟嘌呤。为9-[(2,3-二羟基-1-丙氧基)甲基]鸟嘌呤的制备提供了一种新的合成方法。制备的样品可用于生产中更昔洛韦的质量控制。
9 - [(2,3-Dihydroxy-1-propoxy) methyl] guanine is a related substance of the antiviral drug Ganciclovir contained in the European Pharmacopeia version 8.0 (also referred to as Impurities). In this paper, benzyl glycidyl ether as the raw material, followed by acid-catalyzed ring-opening reaction of epoxy, primary hydroxyl selective protection, secondary hydroxy benzyl etherification, primary hydroxyl deprotection, chloromethyl etherification and substitution reaction side 2,3-Dibenzyloxy-1-acetoxymethoxypropane. 2,3-Dibenzyloxy-1-acetoxymethoxypropane followed by condensation with N2,9-diacetylguanine followed by hydrogenolysis, deprotection and basic hydrolysis to give the target product 9- [(2,3-dihydroxy-1-propoxy) methyl] guanine. Preparation of 9 - [(2,3-dihydroxy-1-propoxy) methyl] guanine provides a new synthetic method. The prepared samples can be used for quality control of ganciclovir in production.