1-deaza-3 `-O-methyladenosine: A nucleoside with the syn-conformation in the solid state and in solution

Abstract

The 2'-O-methyl (2) and the 3'-O-methyl (3) derivatives of 1-deazaadenosine (1) were prepared. Single crystal X-ray analysis as well as H-1 and C-13 NMR studies were performed on the 3'-O-methyl-1-deazaadenosine 3. In the solid state, the glycosyl torsion angle (chi = 64.7 degrees) is in the syn-range which is caused by an intramolecular (5')CH2OH ... N(3) hydrogen bond. The ribofuranose moiety adopts a E-2 (C-3'-exo; S) conformation and the orientation of the exocyclic C(4')-C(5') bond is sc (gamma((+)g)). The conformation in solution was found to be very similar to that in solid state. Whereas the 2'-O-methyl derivative of 1 is a strong inhibitor of adenosine deaminase the 3'-O-methyl derivative is neither inhibitor nor substrate.