Proton magnetic resonance studies of 5,6-saturated thymidine derivatives produced by ionizing radiation. Conformational analysis of 6-hydroxylated diastereoisomers.

The conformational properties of ten 6-hydroxylated dihydrothymidine derivatives including the various diastereoisomers of 5,6-dihydroxy-5,6-dihydrothymidine, 6-hydroxy-5,6-dihydrothymidine and 5-bromo-6-hydroxy-5,6-dihydrothymidine have been studied by 250 MHz proton magnetic resonance in aqueous solutions. A close correlation has been established between the carbon-6 configuration and the osidic conformation. The increase in the amplitude of the puckering within the furanose ring compared to that of thymidine or 2'-deoxyuridine is more pronounced for the levorotatory (6S) nucleosides than for the dextrorotatory (6R) diastereoisomers. The importance of the 2' endo conformer population decreases in the following order: (-) greater than (+) greater than thymidine. The absence of destabilizing effects on the g+ rotameric population about the C(4')-C(5') bond denotes the lack of any interaction between the exocyclic hydroxymethyl group and the 6-hydroxyl function or the 2-keto group. The 5,6-saturated nucleosides adopt a preferential anti conformation. The comparison has been extended to syn nucleosides which show opposite trends in the sugar conformation and g+ distribution.