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 DeltaG values; furthermore, in adenosine, the conformational preference is of enthalpic origin, whereas in the cyclohexenyl congener, the conformational preference is of entropic origin.
Vijgen
Sara
S
Laboratory of Medicinal Chemistry, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Minderbroedersstraat 10, B-3000, Leuven, Belgium.
Nauwelaerts
Koen
K
Wang
Jing
J
Van Aerschot
Arthur
A
Lagoja
Irene
I
Herdewijn
Piet
P
D000241:Adenosine / Q000737:chemistry; D003510:Cyclohexanes / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D003510:Cyclohexanes; D009705:Nucleosides; D000241:Adenosine