The Electronic Nature of the Aglycone dictates the Drive of the Pseudorotational Equilibrium of the Pentofuranose Moiety in C-Nucleosides

Abstract

We herein show for the first time that the specific electronic character of a C-aglycone dictates the thermodynamic preference of the two-state N ? S pseudorotational equilibrium to either N- or S-type sugar. As the electron-deficiency of the C-aglycone increases, a more favourable O4′(n) → σ*(Cl'-C(sp2)) interaction results into anomeric stabilization as indicated by more positive ΔH° for the drive of the N ? S equilibrium to more N-type sugar conformation with pseudoaxial aglycone. Alternatively, as the C-aglycone becomes more electron-rich, an unfavourable O4′(n) → σ*(Cl'-C(sp2)) interaction results into anomeric destabilization as indicated by more negative ΔH° for the drive of the N ? S equilibrium to more S-type sugar conformation with pseudoequatorial aglycone.