Analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbutyl)guanine. Part 1. Substitutions on C-2′ of the acyclic N-9 substituent

Abstract

Syntheses of 9-(4-hydroxy-3-hydroxymethyl-2-methylbutyl)guanine (4), 9-(4-hydroxy-3-hydroxy-methyl-2-methoxybutyl)guanine (5), 9-[4-hydroxy-2,3-bis(hydroxymethyl)butyl]guanine (6), 9-(2,4-dihydroxy-3-hydroxymethylbutyl)guanine (7), and 9-(2-fluoro-4-hydroxy-3-hydroxymethylbutyl)guanine (8) are described. These analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbutyl)guanine (3) were prepared by a route involving alkylation of 2-amino-6-chloropurine with a protected bromide or trifluoromethanesulphonate ester derived from the appropriately substituted alcohol (9a–e). Subsequent hydrolysis and deprotection afforded the required 9-substituted guanine. None of this series of acyclonucleosides (4)–(8) was highly active in antiviral tests in cell cultures.