盐酸缬更昔洛韦及其有关物质的合成

Synthesis of Valganciclovir Hydrochloride and Its Related Substances

更昔洛韦经缩合、选择性水解、氢化还原反应制得盐酸缬更昔洛韦,总收率为29.7%,终产品纯度和非对映异构体比例均符合美国药典35版要求。并合成了工艺中可能存在的3个有关物质:更昔洛韦单乙酸酯、更昔洛韦单丙酸酯和更昔洛韦双缬氨酸酯,为盐酸缬更昔洛韦的质控和纯化提供基础。

Valganciclovir hydrochloride （1） was synthesized from ganciclovir by condensation, selective hydrolysis and hydrogenation with an overall yield of 29.7%. The purity of final product and the ratio of the diastereomeric isomers were in accordance with the requirements of US pharmacopeia （USP35）. Three related substances including ganciclovir monoacetate, ganciclovir monopropionate and bis-valine easter of ganciclovir were successfully synthesized, which provided the basis for the quality control and purification of 1.