1-DEAZA-3'-O-METHYLADENOSINE - A NUCLEOSIDE WITH THE SYN-CONFORMATIONIN THE SOLID-STATE AND IN SOLUTION

The 2'-O-methyl (2) and the 3'-O-methyl (3) derivatives of 1-deazaaden osine (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-deazaadenosin e 3. In the solid state, the glycosyl torsion angle (chi = 64.7 degree s) 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') bon d is + sc (gamma((+)g)). The conformation in solution was found to be very similar to that in solid state. Whereas the 2'-O-methyl derivativ e of 1 is a strong inhibitor of adenosine deaminase the 3'-O-methyl de rivative is neither inhibitor nor substrate.