Structure of cyclic nucleoside phosphonate ester prodrugs: An inquiry

摘要

The configuration at phosphorus in cyclic (S)-HPMPC (1, cidofovir) and (S)-HPMPA (2) phenyl ester (5 and 6, respectively) diastereomers ((R _p)-5, (R _p)-6, (S _p)-6) was determined by X-ray crystallography and correlated to their ~1H and ~(31)P NMR spectra in solution. (R _p)-5 and (R _p)-6 have chair conformations with the nucleobase substituent equatorial and the P-OPh axial. Perhaps surprisingly, (S _p)-6 is (a, a) in the crystal and exists largely as an equilibrium of (a, a)/(e, e) conformers in chloroform or acetonitrile.