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

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 Nor S-type sugar. As the electron-deficiency of the C-aglycone increases, a more favourable O4'(n) σ*(C1'-C(sp2)) interaction results into anomeric stabilization as indicated by more positive ∆Η° 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*(C1'-C(sp2)) interaction results into anomeric destabilization as indicated by more negative ∆Η° for the drive of the N S equilibrium to more S-type sugar conformation with pseudoequatorial aglycone. The unique structural characteristic of C-nucleosides which distinguishes them from the ordinary Nnucleosides is the precense of a carbon to carbon bond instead of a carbon to nitrogen bond between the aglycone and the sugar moieties1. Many C-nucleosides have been isolated as antibiotics and exhibit anticancer and/or antiviral activity2. We have recently shown3u by quantitation of the energetics of pDdependent N S pseudorotational equilibria of the pentofuranose moiety in C-nucleosides that the strength of the anomeric effect of each C-nucleoside is indeed aglycone-dependent3h and tunable3u depending upon the pD of the medium, due to the change in the aromatic character of its nucleobase. It was not however possible in those work3h,u to show directly how a specific electron-rich or electron-deficient character of a C-aglycone promotes the N S pseudorotational equilibria of the constituent sugar! In this work, through a thermodynamic study of the N S pseudorotational equilibria of the sugar moiety of 9 different C-nucleosides 1 94 (note the exact numbering of atoms in the C-aglycones), we unambiguously