Synthesis and Conformational Analysis of a Ribo-Type Cyclohexenyl Nucleoside

A straightforward approach to a novel class of ribo-type cyclohexenyl nucleosides is described. An electron-demand Diels−Alder reaction forms the key-step of the chosen synthetic pathway. Although the difference is small, conformational analysis using NMR shows that this nucleoside analogue adopts preferentially an 2H3 conformation (S-type), while the “deoxy” cyclohexenyl analogue has a preference for a C3‘ endo conformation (N-type). Analyses of the conformational equilibrium reveal that, in the given experimental conditions, the difference between adenosine and its cyclohexenyl congener resides in their different ΔG values; furthermore, in adenosine, the conformational preference is of enthalpic origin, whereas in the cyclohexenyl congener, the conformational preference is of entropic origin.