Synthesis and antiviral activity of (S)-9-[4-hydroxy-3-(phosphonomethoxy)butyl]guanine
- 1 June 1990
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 33 (6) , 1797-1800
- https://doi.org/10.1021/jm00168a039
Abstract
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-[(diethylphosphono)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 derivative (14 and 15) did not exhibit activity against HSV-1 and -2 HCMV.This publication has 24 references indexed in Scilit:
- Herpesvirus infections in the acquired immune deficiency syndromeJAMA, 1984
- Interaction of herpes simplex virus-induced DNA polymerase with 9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate.Journal of Biological Chemistry, 1984
- 9-([2-hydroxy-1-(hydroxymethyl)ethoxy]methyl)guanine: a selective inhibitor of herpes group virus replication.Proceedings of the National Academy of Sciences, 1983
- Unique spectrum of activity of 9-[(1,3-dihydroxy-2-propoxy)methyl]-guanine against herpesviruses in vitro and its mode of action against herpes simplex virus type 1.Proceedings of the National Academy of Sciences, 1983
- Anti-herpesvirus activity of the acyclic nucleoside 9-(1,3-dihydroxy-2-propoxymethyl)guanineAntimicrobial Agents and Chemotherapy, 1983
- Activation by thymidine kinase and potent antiherpetic activity of 2′-nor-2′-deoxyguanosine (2′NDG)Biochemical and Biophysical Research Communications, 1982
- A new nucleoside analog, 9-[[2-hydroxy-1-(hydroxymethyl)ethoxyl]methyl]guanine, highly active in vitro against herpes simplex virus types 1 and 2Antimicrobial Agents and Chemotherapy, 1982
- The activity in vitro against herpes virus of 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine), a new antiviral agentJournal of Antimicrobial Chemotherapy, 1979
- 9-(2-Hydroxyethoxymethyl)guanine activity against viruses of the herpes groupNature, 1978
- Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanineProceedings of the National Academy of Sciences, 1977