A direct method for the preparation of 2-hydroxyethoxymethyl derivatives of guanine, adenine, and cytosine

J Med Chem. 1980 May;23(5):572-4. doi: 10.1021/jm00179a020.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenine / analogs & derivatives*
  • Adenine / chemical synthesis
  • Antiviral Agents / chemical synthesis
  • Cytosine / analogs & derivatives*
  • Cytosine / chemical synthesis
  • Drug Stability
  • Guanine / analogs & derivatives*
  • Guanine / chemical synthesis
  • Methods

Substances

  • Antiviral Agents
  • Guanine
  • Cytosine
  • Adenine