Acyclic Nucleosides. Synthesis and Antiherpetic Activity of 9-[[[2-Hydroxy-1-(Hydroxymethyl)Ethyl]Thio]Methyl]Guanine and 1-[[[2-Hydroxy-1-(Hydroxymethyl)Ethyl]Thio]Methyl]Cytosine |
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| Authors: | James L. Kelley James A. Linn Lilia Beauchamp Peter Collins J. W. T. Selway Karen K. Biron |
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| Affiliation: | 1. Wellcome Research Laboratories, Research Triangle Park , NC, 27709;2. Wellcome Research Laboratories, Langley Court Beckenham , Kent, BR3 3BS, UK |
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| Abstract: | Abstract The synthesis and antiherpetic activity of 9-[[[2-hydroxy-1-(hydroxymethyl)ethyl]thio]methy1]guanine (4) and 1-[[[2-hydroxy-1-(hydroxymethyl)ethyl]thio]methy]cytosine (6), the side-chain thio analogues of ganciclovir (3) and BW A1117U (5), are described. The sidechain synthon 1,3-bis(benzyloxy)-2-[(chloromethyl)thio]propane (11) was prepared in four steps from 1,3-bis(benzyloxy)-2-propanol (7). Alkylation of 2-amino-6-chloro-9H-purine with 11 provided the intermediate 9-substituted-2-amino-6-chloropurine 12, which was conveniently converted to 4 in two steps. Reaction of a fivefold excess of cytosine with 11 provided the desired 1-isomer 14, which was debenzylated to give 6. In contrast with ganciclovir (3) and BW A1117U (5), neither 4 nor 6 had significant in vitro activity against human cytomegalovirus. |
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