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 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.
Boesen
Thomas
T
Department of Chemistry, University of Copenhagen, The H. C. Ørsted Institute, Universitetsparken 5, DK-2100 Copenhagen, Denmark.
Madsen
Christian
C
Pedersen
Daniel Sejer
DS
Nielsen
Brian M
BM
Petersen
Asger B
AB
Petersen
Michael A
MA
Munck
Michael
M
Henriksen
Ulla
U
Nielsen
Claus
C
Dahl
Otto
O
D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002478:Cells, Cultured; D003596:Cytosine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D006147:Guanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000494:pharmacology
D000998:Antiviral Agents; D009705:Nucleosides; D006147:Guanine; D003596:Cytosine; D000225:Adenine