Preparation and antiviral properties of new acyclic, achiral nucleoside analogues: 1- or 9-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]nucleobases and 1- or 9-[2,3-dihydroxy-2-(hydroxymethyl)propyl]nucleobases

Acyclic, achiral nucleoside derivatives 1b-e of adenine, cytosine, 5-methylcytosine, and guanine, containing a 3-hydroxy-2-(hydroxymethyl)prop-1-enyl group on N-1 or N-9, have been prepared analogously to the previously described thymine derivative 1a. In contrast to the adenine and guanine derivati...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2004-04, Vol.2 (8), p.1245-1254
Main Authors: Boesen, Thomas, Madsen, Christian, Pedersen, Daniel Sejer, Nielsen, Brian M, Petersen, Asger B, Petersen, Michael A, Munck, Michael, Henriksen, Ulla, Nielsen, Claus, Dahl, Otto
Format: Article
Language:English
Subjects:
Adenine - analogs & derivatives
Adenine - chemical synthesis
Adenine - pharmacology
Animals
Antiviral Agents - chemical synthesis
Antiviral Agents - pharmacology
Cells, Cultured
Cytosine - analogs & derivatives
Cytosine - chemical synthesis
Cytosine - pharmacology
Guanine - analogs & derivatives
Guanine - chemical synthesis
Guanine - pharmacology
HIV-1 - drug effects
Molecular Structure
Nucleosides - chemical synthesis
Nucleosides - pharmacology
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Summary:Acyclic, achiral nucleoside derivatives 1b-e of adenine, cytosine, 5-methylcytosine, and guanine, containing a 3-hydroxy-2-(hydroxymethyl)prop-1-enyl group on N-1 or N-9, have been prepared analogously to the previously described thymine derivative 1a. In contrast to the adenine and guanine derivatives, the cytosine derivative 9 was unstable, and was obtained in a low yield due to side reactions. These include cleavage of the propenyl group from the base, and the formation of a bicyclic compound. The thymine derivative, although stable under neutral conditions, likewise underwent a reversible cyclization reaction (Michael addition) in the presence of acids or bases. The 5-methylcytosine derivative was stable under neutral and basic conditions. Four other nucleoside derivatives 26a-d containing a 2,3-dihydroxy-2-(hydroxymethyl)propyl group on N-1 or N-9, three of which are new, have likewise been prepared. All compounds were evaluated as antiviral agents against HIV-1 and HSV-1 but were devoid of antiviral activity.
ISSN:1477-0520
1477-0539
DOI:10.1039/b316304k