Intramolecular hydrogen bonding and molecular conformations of nucleosides: uridine derivatives

Abstract

The effect of intramolecular hydrogen bonding on the molecular conformations of uridine derivatives in solution was investigated by i.r., c.d., and n.m.r. spectroscopy. The 220 MHz 1H n.m.r. spectra of three uridine derivatives in CDCl3 solutions [3-methyl-5′-O-methyl-2′,3′-O-isopropylideneuridine (1), 3-methyl-2′,3′-O-isopropylideneuridine (2), 3,6-dimethyl-2′,3′-O-isopropylideneuridine (3)] were analysed in terms of the conformational properties of the O(5′)–C(5′) and C(5′)–C(4′) bonds, and the sugar ring conformation. The presence of the hydrogen bond in compounds (2) and (3) was confirmed directly by i.r. measurements whereas 5′-O-methylation precludes such hydrogen bond formation between the exocyclic CH2OH group and the base ring 2-carbonyl group in compound (1). The presence of the hydrogen bond was confirmed indirectly by c.d. measurements which showed that the base ring adopts the syn-conformation which is necessary for such hydrogen bond formation whereas the base ring of the 5′-O-methyl compound adopts a predominant anti-conformation. Changes in conformational properties of compound (2) in different solvents monitored by c.d. and n.m.r. measurements support the conformational model that hydrogen bond formation between the exocyclic CH2OH group and the pyrimidine ring 2-carbonyl group necessitates the base ring being in the syn-conformation and the O(5′)–C(5′) and C(5′)–C(4′) bonds adopting specific gauche-conformers. Hydrogen bond formation also promotes the sugar ring S [ca. C(2′)-endo] conformation though not as markedly as for an analogous purine derivative.