喷昔洛韦的合成工艺研究

Improved Synthesis of Penciclovir

关键词:  喷昔洛韦  抗病毒药物  合成

Key words:  penciclovir  antiviral drug  synthesis

摘要:

目的以4-溴-2,2-二甲氧羰基-丁酸甲酯为原料合成新型抗病毒药物喷昔洛韦。方法采用2-氨基-6-氯嘌呤位置有择烷基化反应，缩合产物不经分离直接脱羧、还原、酰化、水解得到目标产物。结果总收率由文献的27%提高到33.1%。产物结构经元素分析、质谱、核磁共振氢谱及碳谱得到确证。结论该工艺简化了后处理操作，降低了原料成本，更易于工业化生产。

Abstract:

OBJECTIVE To study the synthetic route of penciclovir, a kind of new antiviral drug, was synthesized with methyl 4-bromo-2, 2-bis-methoxycarbonyl-butyrate as raw material. METHODS Target compound was synthesized by means of the regioselective alkylation of 2-amino-6-chloropurine as a pivotal step, followed by decarboxylation, reduction, acetylation, and hydrolysis without separation of the products. RESULTS The total yield was amount to 33%, higher than literature. The target molecule was confirmed by MS, elementary analysis, 1H-NMR and 13C-NMR. CONCLUSION The improved process can be easily operated and is suitable for a scale production.