文章基本信息

标题：Antiviral nucleoside diphosphate diglycerides: improved synthesis and facilitated purification.
本地全文：下载
作者：G M van Wijk ; K Y Hostetler ; H van den Bosch 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：1992
卷号：33
期号：8
页码：1211-1219
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Cytidine diphosphate diglyceride and its analogs have previously been synthesized by condensing phosphatidic acid with the monophosphomorpholidates of the various nucleosides. Yields have been low and purification of the product has been difficult. We report here an improved method for the synthesis of nucleoside diphosphate diglycerides with potential antiviral activity. Phosphatidic acid was activated with morpholine in the presence of dicyclohexylcarbodiimide to phosphatidic acid morpholidate. This compound was condensed with the 5'-monophosphate of the anti-HIV agents 3'-azido-3'-deoxythymidine, 3'-deoxythymidine or 2',3'-dideoxycytidine, and the monophosphate of the anti-HSV agent acyclovir. The resulting nucleoside diphosphate diglycerides are potential candidates for improved antiviral action when compared to the parent nucleoside analogs. Compared to the older method for the preparation of cytidine diphosphate diglyceride and analogs thereof, the new method has several advantages: reaction times are reduced from several days to several hours and the yield of the reactions is generally increased from 20-40% to between 50 and 80%. In addition, the purification of the compounds is greatly facilitated due to the small amount of phosphatidic acid remaining in the reaction mixture.