Synthesis of novel conformationally locked carbocyclic nucleosides derived from 2-(hydroxymethyl)bicyclo[2.2.1]heptane

58 Abstract A new synthetic pathway to novel conformationally locked carbocyclic nucleosides containing 2-(hydroxymethyl)bicyclo [2.2.1]heptane was elaborated. (1R*,2R*,4R*,6R*)-6- and (1R*,2R*,4R*,5S*)-5- (Hydroxymethyl)bicyklo[2.2.1]heptan-2-ol was synthetised as a key intermediate from comertially available dicyclopentadiene and methylacrylate. Racemic karbocyclic nukleosides (1R*,2R*,4S*,6S*)-6- and [(1R*,2S*,4R*,5S*)-5-(6-chloro-9H-purin-9-yl)bicyclo[2.2.1]hept-2-yl]methanol were synthetised by Mitsunobu reaction of (1R*,2R*,4R*,6R*)-6- or (1R*,2R*,4R*,5S*)-5-(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol with 6-chlorpurine. Racemic karbocyclic nukleosides bearing adenine ring, 6-cyclopropylaminopurine ring, 6-dimethylaminopurine ring or 6-thiopurine ring were synthetised by substitution of chlorine of 6-chlorpurine ring. Racemic karbocyclic nukleosides bearing thymine ring (1- [(1R*,2S*,4S*,6R*)-6- and 1-[(1R*,2S*,4R*,5S*)-5- (hydroxymethyl)bicyclo[2.2.1]hept-2-yl]-5-methylpyrimidine-2,4(1H,3H)-dione) were synthetised by reaction of 5- or 6-aminobicyclo[2.2.1]hept-2-yl methanol with ethyl [(2E)-3-ethoxy-2-methylprop-2-enoyl]carbamate. The 5- or 6- aminobicyclo[2.2.1]hept-2-yl methanol was prepared in three simple steps from the key intermediate 5- or 6-(hydroxymethyl)bicyclo[2.2.1]heptan-2-ol. All..