title: 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.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Copenhagen, The H. C. Ørsted Institute, Universitetsparken 5, DK-2100 Copenhagen, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Boesen
authors.forename: Christian
authors.initials: C
authors.lastname: Madsen
authors.forename: Daniel Sejer
authors.initials: DS
authors.lastname: Pedersen
authors.forename: Brian M
authors.initials: BM
authors.lastname: Nielsen
authors.forename: Asger B
authors.initials: AB
authors.lastname: Petersen
authors.forename: Michael A
authors.initials: MA
authors.lastname: Petersen
authors.forename: Michael
authors.initials: M
authors.lastname: Munck
authors.forename: Ulla
authors.initials: U
authors.lastname: Henriksen
authors.forename: Claus
authors.initials: C
authors.lastname: Nielsen
authors.forename: Otto
authors.initials: O
authors.lastname: Dahl
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D009705:Nucleosides; D006147:Guanine; D003596:Cytosine; D000225:Adenine