Collect. Czech. Chem. Commun. 2009, 74, 487-502
Published online 2009-03-13 09:20:30

Synthesis of novel carbocyclic nucleoside analogues derived from 7-oxabicyclo[2.2.1]heptane-2-methanol

Hubert 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


Hydroboration of [(1R*,2R*,4R*)-7-oxabicyclo[2.2.1]hept-5-en-2-yl]methyl benzoate (5), which was prepared by Diels–Alder reaction of furan with acrolein and subsequent reduction and benzoylation of the Diels–Alder product, afforded [(1R*,2S*,4S*,6S*)-6-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (6) and [(1R*,2R*,4R*,5S*)-5-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (7). The key intermediates, [(1R*,2S*,4S*,6R*)-6-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (10) and [(1R*,2R*,4R*,5R*)-5-hydroxy-7-oxabicyclo[2.2.1]heptan-2-yl]methyl benzoate (11), were prepared from 6 and 7, respectively, by oxidation with pyridinium dichromate and subsequent reduction of the thus obtained ketones. The Mitsunobu reaction of 10 and 11 with 6-chloropurine and subsequent reductive deprotection with diisobutylaluminium hydride afforded 6-chloropurine derivatives, which were converted to other purine analogues. Thymine analogues were prepared by Mitsunobu reaction of 10 and 11 with 3-benzoyl-5-methylpyrimidine-2,4(1H,3H)-dione and subsequent methanolysis. The target compounds were tested for the activity against Coxsackie virus.

Keywords: Nucleosides; Carbocyclic nucleosides; Purines; Adenine; Thymine; 5-Methylpyrimidine-2,4(1H,3H)-dione; 6-Chloropurine; 6-(Dimethylamino)purine; 6-(Cyclopropylamino)purine; Mitsunobu reaction; Coxsackie virus.

References: 27 live references.