Nucleosides. 154. 2'-Azido-2',3'-dideoxypyrimidine nucleosides. Synthesis and antiviral activity against human immunodeficiency virus
- 1 June 1990
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 33 (6) , 1663-1666
- https://doi.org/10.1021/jm00168a020
Abstract
A series of four 2''-azido-2'',3''-dideoxypyrimidine nucleosides were synthesized and their activity against human immunodeficiency virus was explored. 2,2''-Anhydro-5-O-benzoyluridine (6a) was prepared from 5-O-benzoyluridine (5a) and coverted into 3''-deoxy analogue 8a by imidazoylthiocarbonylation followed by Bu3SnH reduction. Treatment of 8a with LiN3 in DMF followed by saponification afforded 2''-azido-2'',3''-dideoxyuridine (1a). The 5''-O-benzoylated nucleoside 9a was further converted into the 5-bromo and 5-iodo analogues (1b and 1c) by halogenation and debenzoylation. 2'',3''-O-Isopropylideneuridine (3) was converted into two steps into the thymidine nucleoside, which was benzoylated and de-O-isopropylidenated to affort 5''-O-benzoyl-5-methyluridine (5d). 2''-Azido-2'',3''-dideoxy-5-methyluridine (1d) was synthesized from 5d in a similar manner as that used for the synthesis of 1a from 5a. These new nucleosides, closely related to AZT, however, did not exhibit any significant anti-HIV activity in tissue culture using H9 cells.This publication has 15 references indexed in Scilit:
- Synthesis and antiviral activity of various 3'-azido, 3'-amino, 2',3'-unsaturated, and 2',3'-dideoxy analogs of pyrimidine deoxyribonucleosides against retrovirusesJournal of Medicinal Chemistry, 1987
- Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase.Proceedings of the National Academy of Sciences, 1986
- Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides.Proceedings of the National Academy of Sciences, 1986
- 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro.Proceedings of the National Academy of Sciences, 1985
- Isolation of Human T-Cell Leukemia Virus in Acquired Immune Deficiency Syndrome (AIDS)Science, 1983
- Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS)Science, 1983
- Partial protection of carbohydrate derivatives. Part 3. Regioselective 2′-O-deacylation of fully acylated purine and pyrimidine ribonucleosides with hydrazine hydrateJournal of the Chemical Society, Perkin Transactions 1, 1979
- Reactions of relevance to the chemistry of aminoglycoside antibiotics. Part 7. Conversion of thiocarbonates into deoxy-sugarsJournal of the Chemical Society, Perkin Transactions 1, 1977
- Introduction of an azide group into some uridine derivatives via 2',3'-benzoxonium and 2'-3'-azidonium intermediatesThe Journal of Organic Chemistry, 1976
- Nucleotides. V. Purine Ribonucleoside 2',3'-Cyclic Carbonates. Preparation and Use for the Synthesis of 5'-Monosubstituted Nucleosides*Biochemistry, 1966