The replacement of the furanose ring by a cyclopentane in nucleosides generates a series of analogues known as carbocyclic nucleosides, which show increased chemical and enzymatic stability because the glycosidic bond is absent.1 However, the loss of such glycosidic bond leads to a significant change in conformation due to the absence of anomeric effect and gauche effect that help maintain the furanose ring in either 3’-endo (north) or 2’-endo (south) conformation in conventional nucleosides.2 Fusing a carbocyclic ring to a cyclopentane should be able to lock the embedded cyclopentane ring into a conformation similar to that in conventional nucleosides.3 Herein, syntheses of conformation constrained carbobicyclic nucleosides with a novel bicycle[4.3.0]nonane system, will be reported. Nucleoside 1 could be derived from ketone 2 which would be assembled from enone 3 via an intramolecular Diels Alder reaction as the key step. Enone 3 would be accessed from D-ribose (5).
Reference
1.AgrofoglioL.,Farese A., Condom R., Challand S. R.,Earl R. A.,Tetrahedron1994,50,10611.
2.Saenger W.,Principles of Nucleic Acid Structure, p.9, Cantor, C. E.Ed.Springer-Verlag,New York,1984.
3.Marquez V. E., Ezzitouni A., Russ P., Siddiqui M. A., Ford H., Feldman R. J., Mitsuya H., George C.and Barchi Jr J. J.,J. Am. Chem. Soc.1998,120, 2780.
