Enantioselective Synthesis and Conformational Study of Cyclohexene Carbocyclic Nucleosides

Enantioselective synthesis of a new family of unsaturated six-membered carbocyclic nucleosides using ( R )-(−)-carvone as starting material is described. Introduction of the base moiety via Mitsunobu reaction proceeded regio- and stereoselectively and with good chemical yield, while the Pd-coupling approach failed. 1 H NMR study and molecular modeling show the adenine compound exists in an equilibrium of 3 H 2 and 2 H 3 conformers (ratio 7:3) in favor of the 3‘-endo half-chair conformation, with the base oriented in a pseudoaxial position. This conformational preference can be explained by the π → σ* C1 ‘ - N1 interaction involving the antibonding orbital of the C1‘−N bond.