The synthesis of (S)-9-[4-hydroxy-3-(phosphonomethoxy)butyl]guanine (3), starting from (S)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane (4), is described. Alkylation of trityl derivative 7 with (diethylphosphono)methyl triflate provided phosphonate 8, which was readily converted to mesylate 12 in three steps. Nucleophilic substitution of the mesylate group of 12 by 2-amino-6-chloropurine sodium salt led to (S)-2-amino-6-chloro-9-[3-[(diethyl-phosphono)methoxy]-4-(tetrahydro- 2H-pyran-2-yloxy)butyl]purine (13). Sequential treatment of 13 with trimethylsilyl bromide and then with 2 N HCl furnished 3. Preliminary in vitro screening indicated that 3 exhibited a potent activity against human cytomegalovirus (HCMV) but was not active against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). The adenine and cytosine derivatives (14 and 15) did not exhibit activity against HSV-1 and -2 and HCMV.