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 P2, 2, 2, .with Z = 4 in a unit cell of dimensions: a = 16.48(1), b = 4.752(4), and c = 15.94(1) A. 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 23") has the C(2')endo S-conformation, the glycosidic torsion angle lies in the normal anti range (xCN 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) (2.696 A) and O(4) * * * O(5') (2.907 A) hydrogen bonds. lH 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')-0(5') side-chain shows almost equal populations of gauche-gauche-and gauche-trans-rotamers with a minor contribution of the transgauche-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.KNOWLEDGE of conformation and geometry of fragments of nucleic acids or their analogues may be helpful for the interpretation of physical data (n.m.r., c.d.), for correlation with tRNA structures and, more generally, helical structures of nucleic acids. 0 endo R1=H, R2=OMe (S) ex0 R1=OMe, Ra=H (R)

Principles of Nucleic Acid Structure

“…As in unmodified nucleosides, these are in rapid equilibrium. The syn ~anti distribution, however, is shifted in favor of syn according to nuclear magnetic resonance data (603,605). Conformationally locked nucleosides offer a unique system to calibrate spectroscopic methods and to test biological systems for their specificity.…”

“…Owing to the inherent flexibility of nucleosides, spectral assignment of structural features is difficult because the dynamic sugar puckering equilibrium occurs simultaneously with correlated rotational movements about the exocyclic C 4 ,-C S ' and glycosyl C1,-N bonds (Section 4.13). If one or all of these conformational freedoms are blocked, interpretation of ORD, CD, and NMR spectroscopic data can be put on safer grounds (599,603,(606)(607)(608)(609)(610). One must keep in mind, however, that the chemical modification used to bridge sugar and base could well alter the spectroscopic signals relative to unmodified nucleosides.…”

NMR studies of the conformations and interactions of substrates and ribonucleotide templates bound to the large fragment of DNA polymerase I

“…All other components and conditions were as described in footnote c. 'Low maximal velocity was due to the low concentration of template (590 µ in nucleotides). in four independent crystal structures of uracil-containing compounds: uridine (Green et al, 1975), 3'-UMP (Srikrishnan et al, 1979), 2',3'-O-(methoxymethylene)uridine (de Kok et al, 1977), and 3',5'-diacetyluridine (de Graaff et al, 1977).2…”

“…in four independent crystal structures of uracil-containing compounds: uridine (Green et al, 1975), 3'-UMP , 2',3'-0-(methoxymethy1ene)uridine (de Kok et al, 1977), and 3',5'-diacetyluridine (de Graaff et al, 1977). Even so, partial degradation of the templates in the presence of high concentrations of enzyme was observed.…”

Peptide Ribonucleic Acids (PRNA). 2. A Novel Strategy for Active Control of DNA Recognition through Borate Ester Formation

“…Thus, if nucleobase orientation could be switched by an additive, the external control of recognition behavior can be readily applied. Unfortunately, no external agent or factor, which affects the syn−anti orientation and therefore the recognition behavior of nucleic acids and analogues has been found or proposed to date, although the unusual syn orientation is known to be induced by several internal factors, such as increased steric hindrance and altered sugar puckering. , Indeed, bulky substituents introduced at the 6-position of the pyrimidine base induce the syn orientation in the pyrimidine nucleosides, while ketalization of the cis -2‘,3‘-diol of uridine ( 1 ) enhances the syn/anti ratio of the resulting 2‘,3‘- c UMP or 2‘,3‘- O -isopropylidene uridine through the imposed 2‘,3‘-planar- O 4 ‘ - exo -furanose structure . However, the energetically disfavored syn orientation has not been induced by external agents.…”