盐酸伐昔洛韦有关物质的合成

Synthesis of Related Substances of Valaciclovir Hydrochloride

为了控制抗病毒药盐酸伐昔洛韦产品质量,分别合成了欧洲药典7.0版收载的两个有关物质:以氢化钠为碱,在乙二醇二丁醚中用N-Cbz伐昔洛韦分别与碘甲烷和碘乙烷反应生成N-甲基-N-Cbz伐昔洛韦和N-乙基-N-Cbz伐昔洛韦,随后在钯炭催化下氢解脱保护制得N-甲基伐昔洛韦(2)和N-乙基伐昔洛韦(3)。该方法是立体位阻较大的N-Cbz氨基酸衍生物的N-烷基化反应的改进方法。

To perform the quality control of antiviral agent valaciclovir hydrochloride, two related substances recorded in EP 7.0, N-methylvalaciclovir and N-ethylvalaciclovir, were synthesized from N-Cbzvalaciclovir by N-alkylation with methyliodide and ethyliodide respectively to give N-Cbz-N-methylvalaciclovir or N-Cbz-N- ethylvalaciclovir, which were subjected to deprotection catalyzed by Pd/C. It is an improved method for the N-alkylation of sterically hindered N-Cbzamino acid derivatives.