A comparative conformational study of certain 2'-deoxy-2'-fluoro-arabinofuranosylcytosine nucleosides.

The 270 MHz proton NMR spectra of 2'-deoxy-2'-fluoro-beta-D-arabinofurano-syl-5-iodocytosine as well as the respective 5-bromo and 5-chloro derivatives have been iteratively analyzed using LAOCOON 3. The derived parameters indicate that the fluorine substituent in an arabino configuration results in an approx. 50 : 50 C(3')-endo C(2')-endo conformer mixture. The C(4')--C(5') rotamer populations are 41% gg, 18% tg, and 41% gt. These equilibrium distributions, which are maintained within the series studied, are similar to that of other ara-C derivatives, but quite different from that of 2'-deoxycytidine. The agreement in chemical shift for each of the furanose protons within the series studied suggests a similar syn, anti distribution for each analog.