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: (-) > (+) > 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. © 1979.