Collect. Czech. Chem. Commun. 2009, 74, 469-485
Published online 2009-03-11 10:17:16
Synthesis of novel racemic carbocyclic nucleoside analogues derived from 4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol and 4-oxatricyclo[4.3.1.03,7]decane-10-methanol, compounds with activity against Coxsackie virusesHubert Hřebabeckýa,*, Martin Dračínskýa, Armando M. De Palmab, Johan Neytsb and Antonín Holýa
a 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
b Katholieke Universiteit Leuven, Rega Institute for Medical Research, Minderbroedersstraat 10, BE-3000, Leuven, Belgium
(1R*,2R*,3R*,4S*)-7-Oxabicyclo[2.2.1]hept-5-ene-2,3-dimethanol (10) and (1R*,2R*,3R*,4S*)-bicyclo[2.2.2]oct-5-ene-2,3-dimethanol (14), which were prepared by the Diels–Alder reaction and subsequent reduction with lithium aluminium hydride, were treated with benzyl azidoformate to give benzyl N-[(1R*,2R*,3S*,6S*,7S*,9S*)-9-(hydroxymethyl)-4,8-dioxatricyclo[4.2.1.03,7]nonan-2-yl]carbamate (11) and benzyl N-[(1R*,2R*,3R*,6R*,7S*,10S*)-10-(hydroxymethyl)-4-oxatricyclo[4.3.1.03,7]decan-2-yl]carbamate (15). Hydrogenolysis of carbamates 11 or 15 afforded (1R*,2R*,3S*,6S*,7S*,9S*)-2-amino-4,8-dioxatricyclo[4.2.1.03,7]nonane-9-methanol (12) or (1R*,2R*,3R*,6R*,7S*,10S*)-2-amino-4-oxatricyclo[4.3.1.03,7]decane-10-methanol (16). The amines 12 and 16 were transformed to thymine and purine nucleoside analogues. The target compounds were tested for the activity against Coxsackie virus.
Keywords: Amines; Nucleosides; Carbocyclic nucleosides; Purines; Adenine; Thymine; 5-Methylpyrimidine-2,4(1H,3H)-dione; 6-(Dimethylamino)purine; 6-(Cyclopropylamino)purine; 9H-Purine-6-thiol; Coxsackie virus; Antivirals.
References: 25 live references.