Synthesis and antiviral activity of acyclic nucleosides with a 3(S),5-dihydroxypentyl or 4(R)-methoxy-3(S),5-dihydroxypentyl side chain.

Abstract

Optically pure acyclic nucleoside analogues with a 3(S),5-dihydroxypentyl or 4(R)-methoxy-3(S),5-dihydroxypentyl side chain were synthesized starting from 2-deoxy-D-ribose. The acyclic nucleosides were obtained by alkylation of the bases with the mesylates 16 and 17. Of these series of novel nucleoside analogues only 9-[3(S),5-dihydroxypent-1-yl]guanine (6d) showed marked antiviral activity. It inhibited the cytopathogenicity of herpes simplex virus type 1 (HSV-1) at a concentration of 0.4-0.6 microgram/mL, which thus points to a greater antiviral activity than recently reported for the mixture of the R and S enantiomers (12.5 micrograms/mL). In contrast with 6d, its 4(R)-methoxy derivative 7d did not show antiviral activity, which implies that the 4'-methoxy group is unable to mimic the 1',4'-oxygen bridge of the normal furanose ring.