Crystal structure and molecular conformation of 2′,3′-O-methoxymethyleneuridine: X-ray and nuclear magnetic resonance investigation

Abstract

Crystals of the title compound are orthorhombic, space group P2₁2₁2₁, with Z= 4 in a unit cell of dimensions: a= 16.48(1), b= 4.752(4), and c= 15.94(1)Å. The structure was determined from three-dimensional diffractometer data by direct methods, and refined by least-squares methods to R 4.04%. The dioxolan and ribofuranose rings are cis-connected about the C(2′)–C(3′) bond. The relatively flattened ribose ring (ϕ_max. 23°) has the C(2′)-endo S-conformation, the glycosidic torsion angle lies in the normal anti range (χ_CN 56.5°) and the orientation of the C(5′)–O(5′) side-chain is gauche–gauche. The crystal packing is governed by O(2) N(3)(2.896 Å) and O(4) O(5′)(2.907 Å) hydrogen bonds. ¹ H n.m.r. spectroscopy reveals the existence of various conformational equilibria in solution. Vicinal coupling constants between ribose protons are consistent with an N [C(3′)-endo] S [C(2′)-endo] equilibrium with a slightly more puckered ribose ring than occurs in the crystal structure. The C(5′)–O(5′) side-chain shows almost equal populations of gauche–gauche- and gauche–trans-rotamers with a minor contribution of the trans–gauche-conformation. The c.d. spectrum and the chemical shifts of the base protons H(5) and H(6) indicate a preference for the anti-conformation about the glycosidic bond.