Journal of Lipid Research, Vol 33, 1211-1219, Copyright © 1992 by Lipid Research, Inc.
Antiviral nucleoside diphosphate diglycerides: improved synthesis and facilitated purification
GM van Wijk, KY Hostetler and H van den Bosch
Center for Biomembranes and Lipid Enzymology, University of Utrecht, The Netherlands.
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.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
