Analogues of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbutyl)guanine. Part 3. Modification of a 3′-hydroxymethyl group

Abstract

Syntheses of 3′-hydroxymethyl modified analogues of the potent antiviral agent 9-(4-hydroxy-3-hydroxymethylbutyl)guanine (1c) are described. These include methyl homologues (7a, b), chain-extended compounds such as the methylene homologue (16) and hydroxyalkyl ethers (26b, c), and methoxy (26a), bromo (28), azido (29), amino (30), and formamido (31) substituted analogues. Compounds (7a, b), (16), and (26a–c) were prepared by construction of an appropriately functionalised alkyl unit followed by purine alkylation and deprotection, whereas compounds (28)–(31) were prepared by selective modification of (1c). The formamido analogue (31) showed moderate anti-herpes virus activity and compounds (16), (26b), and (29) weak activity.