S. Megati et al., O-(5',16)-METHANOCYTIDINE - SYNTHESIS, CONFORMATIONAL PROPERTIES AND DEAMINATION BY CYTIDINE DEAMINASE, Nucleosides & nucleotides, 13(10), 1994, pp. 2151-2168
The synthesis of O-5',O-6-methanocytidine (4), a pyrimidine nucleoside
restricted to the anti conformation, is described. Molecular modeling
studies suggest that 4 is more flexible than conventional cyclonucleo
sides because of its larger-than-usual bridging system and that it can
exist in a number of low energy conformations where the glycosyl rota
tion angles (chi) cover an similar to 80 degrees segment of the anti r
ange. However, while both N-type (C2'-exo) and S-type (C3'-exo) sugar
puckerings are possible, none of the low energy conformers adopt the C
3'-endo or C2'-endo puckering modes generally seen for unconstrained n
ucleosides. The lowest energy conformer predicted for 4 (chi = -152 de
grees, gamma = 73 degrees, P = 206 degrees) is similar to the X-ray st
ructure of a related compound, namely 5-hydroxy-O-5',O-6-methanouridin
e (12, chi = -138 degrees, gamma = 63 degrees, P = 200 degrees). In so
lution, NMR evidence suggests an equilibrium between C2'-exo and C3'-e
xo puckerings for 4, and CD evidence suggests an average glycosyl rota
tion angle (chi) of around -160 degrees. O-5',O-6-Methano-cytidine (4)
is slowly deaminated by crude cytidine deaminase from mouse liver to
give O-5',O-6-methanouridine (3). Assuming that 4 interacts with the n
ormal active site, it is concluded that cytidine deaminase from that p
articular source requires its ordinary substrates to adopt the anti co
nformation.