How does the steric effect drive the sugar conformation in the 3′-C-branched nucleosides?

Abstract

The steric effect of 3′-CH₂OH group drives the North⇄ South pseudorotational equilibrium of the sugar moiety in the isomeric 1-(2′,3′-dideoxy-3′-hydroxymethyl-β-D-erythro-pentofuranosyl)cytosine 1(80% North at 298 K; ΔH°=+5.9 kJ mol^–1, ΔS°=+7.4 J K^–1 mol^–1), and 1-(2′,3′-dideoxy-3′-hydroxymethyl-β-D-threo-pentofuranosyl)cytosine 2(82% South at 293 K; ΔH°=–0.9 kJ mol^–1, ΔS°=+9.5 J K^–1 mol^–1) and it is found to be three times stronger in 2(ΔH°=–5.9 kJ mol^–1) in comparison with that of 1(ΔH°=–2.1 kJ mo^–1).