title: Synthesis, characterization and some properties of dideoxynucleoside analogs of cytidine diphosphate diacylglycerol.
abstract: Phospholipid conjugates of antiretroviral nucleoside analogs have been proposed to have several advantageous features when compared to the parent drugs (Hostetler, K.Y. et al. (1990) J. Biol. Chem. 265, 6112-6117). Here we report on the synthesis of one such type of lipid conjugates, i.e., nucleosides diphosphate diacylglycerols. The syntheses of 3'-azido-3'-deoxythymidine diphosphate diacylglycerol, 3'-deoxythymidine diphosphate diacylglycerol and 2',3'-dideoxycytidine diphosphate diacylglycerol (with different acyl chains) were performed starting from phosphatidic acid and the antiviral nucleoside. A high-performance liquid chromatography procedure for a single step purification of the compounds is presented. The compounds were characterized biochemically, using rat liver enzymes and chemically by phosphorus, fatty acid, ultraviolet, IR and 1H-NMR analyses. Preliminary data on the behaviour in aqueous solution of some of the compounds are presented.
authors.affiliation: Center for Biomembranes and Lipid Enzymology, University of Utrecht, Netherlands.
authors.forename: G M
authors.initials: GM
authors.lastname: van Wijk
authors.forename: K Y
authors.initials: KY
authors.lastname: Hostetler
authors.forename: C N
authors.initials: CN
authors.lastname: Suurmeijer
authors.forename: H
authors.initials: H
authors.lastname: van den Bosch
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D003845:Deoxycytosine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D004075:Diglycerides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D006678:HIV / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D013942:Thymine Nucleotides / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D003845:Deoxycytosine Nucleotides; D004075:Diglycerides; D013942:Thymine Nucleotides