Comprehensive structural studies of 2',3'-difluorinated nucleosides: comparison of theory, solution, and solid state.
J Am Chem Soc
; 130(28): 9048-57, 2008 Jul 16.
Article
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| MEDLINE
| ID: mdl-18558684
ABSTRACT
The conformations of three 2',3'-difluoro uridine nucleosides were studied by X-ray crystallography, NMR spectroscopy, and ab initio calculations in an attempt to define the roles that the two vicinal fluorine atoms play in the puckering preferences of the furanose ring. Two of the compounds examined contained fluorine atoms in either the arabino or xylo dispositions at C2' and C3' of a 2',3'-dideoxyuridine system. The third compound also incorporated fluorine atoms in the xylo configuration on the furanose ring but was substituted with a 6-azauracil base in place of uracil. A battery of NMR experiments in D 2O solution was used to identify conformational preferences primarily from coupling constant and NOE data. Both (1)H and (19)F NMR data were used to ascertain the preferred sugar pucker of the furanose ring through the use of the program PSEUROT. Compound-dependent parameters used in the PSEUROT calculations were newly derived from complete sets of conformations calculated from high-level ab initio methods. The solution and theoretical data were compared to the conformations of each molecule in the solid state. It was shown that both gauche and antiperiplanar effects may be operative to maintain a pseudodiaxial arrangement of the C2' and C3' vicinal fluorine atoms. These data, along with previously reported data by us and others concerning monofluorinated nucleoside conformations, were used to propose a model of how fluorine influences different aspects of nucleoside conformations.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Uridina
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos