화학공학소재연구정보센터
Journal of the American Chemical Society, Vol.116, No.18, 8033-8037, 1994
Quantitation of the Anomeric Effect in Adenosine and Guanosine by Comparison of the Thermodynamics of the Pseudorotational Equilibrium of the Pentofuranose Moiety, in N-Nucleosides and C-Nucleosides
The effect of N-aglycones at C1’ on the drive of two-state north (N(C3’-endo-C2’-exo)) reversible arrow south (S(C2’-endo-C3’-exo)) pseudorotational equilibrium in beta-D-ribofuranosyl-N-nucleosides consists of two counteracting contributions from (i) the anomeric effect (stereoelectronic interactions between furanose O4’ and the nucleobase nitrogen at C1’), which places the aglycone in the pseudoaxial orientation, and (ii) the inherent steric effect of the nucleobase, which opposes the anomeric effect by its tendency to take up pseudoequatorial orientation. The maximum pseudoequatorial orientation of the nucleobase is sterically possible only in the S-type conformations. Therefore, the extent of this pseudoequatorial orientation can be experimentally determined by the extent of the thermodynamic stabilization of the S conformer in the two-state N reversible arrow S equilibrium (ref 1). This means that a direct measurement of the extent of thermodynamic stabilization of the S conformer amongst a set of various beta-D-ribofuranosyl-C-nucleosides, where the absence of the anomeric effect has been previously established from X-ray studies (ref 6), should give us a reference point for the maximally pseudoequatorially oriented C-nucleobase. We report here the characterization of this reference beta-D-ribofuranosyl-C-nucleoside. The subtraction of the Delta H degrees of its pseudorotational equilibrium from the Delta H degrees of beta-D-ribofuranosyl-N-nucleosides gave the quantitative insight of the anomeric effect in adenosine (+9.1 kJ/mol) and guanosine (+10.5 kJ/mol) for the first time. We have found that the C-aglycones in formycin A (1) and B (2) constitute the optimal reference point (ref 12) for our Purpose because they take up the predominantly favored pseudoequatorial orientation (closer to the limit), where the steric control is almost the exclusive determinant, owing to the negligible presence of any stereoelectronic interaction with the lone pairs of furanose-04’ (see Table 3).