Collect. Czech. Chem. Commun. 2007, 72, 1523-1544

Synthesis of Novel Carbocyclic Nucleoside Analogues Derived from 2-(Hydroxymethyl)bicyclo[2.2.1]heptane

Milan Dejmek, Hubert Hřebabecký*, Martin Dračínský and Antonín Holý

Centre for New Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., 166 10 Prague 6, Czech Republic


The key intermediates, [(1R*,2R*,4R*,6R*)-6- (12a) and [(1R*,2R*,4R*,5S*)-5-(hydroxymethyl)- bicyclo[2.2.1]heptan-2-yl]methyl benzoates (12b), were prepared from (1R*,2S*,4R*)- bicyclo[2.2.1]hept-5-en-2-ylmethyl benzoate by hydroboration, oxidation with pyridinium dichromate and subsequent reduction of the thus obtained ketones. The Mitsunobu reaction of 12a and 12b with 6-chloropurine afforded 6-chloropurine derivatives, which were converted into others purine analogues. Thymine analogues were prepared from [(1R*,2R*,4S*,6S*)-6- (25a) and [(1R*,2S*,4R*,5S*)-5-aminobicyclo[2.2.1]heptan-2-yl]methanols (25b), which were prepared from alcohols 12a and 12b in several easy steps.

Keywords: Amines; Nucleosides; Carbocyclic nucleosides; Purines; Norbornanes; Bicyclic nucleosides; Antivirals; Mitsunobu reaction.

References: 21 live references.