A direct method for the preparation of 2-hydroxyethoxymethyl derivatives of guanine, adenine, and cytosine.
Alkylation of 2-chloro-6-iodopurine with iodomethyl [(trimethylsilyl)oxy]ethyl ether at -63 degrees C and subsequent treatment of the 9-substituted chloroiodopurine with K2CO3 in aqueous dioxane at 25 degrees C and then with NH3 under pressure at 150 degrees C provided 9-[(2-hydroxyethoxy)methyl]guanine (1a), a potent antiviral agent against Herpes simplex virus type 1, in excellent yield. Its monophosphate (1g), which is enzymatically produced from 1a in the virus-infected cell, was also synthesized. 6-Chloropurine and 4-(methylthio)pyrimidin-2-one anions were similarly alkylated with iodomethyl [(trimethylsilyl)oxy]ethyl ether, and the products (1f and 2b) were transformed by treatment with methanolic NH3 at 110 degrees C into 9-[(2-hydroxyethoxy)methyl]adenine (1b) and 1-[(2-hydroxyethoxy)methyl]cytosine (2a), respectively. The syntheses of these analogues, heretofore difficult to prepare by a simple procedure, have been conveniently accomplished.
D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000998:Antiviral Agents / Q000138:chemical synthesis; D003596:Cytosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D004355:Drug Stability; D006147:Guanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D008722:Methods
D000998:Antiviral Agents; D006147:Guanine; D003596:Cytosine; D000225:Adenine