Conformational properties of diastereomeric 5'-O-DMT-2'deoxythymidine 3'-O-(S-methyl-methanephosphonothiolate)s and -(se-methyl-methanephosphonoselenolate)s in solution as studied by NMR methods

Abstract

Stereochemical characterization of diastereomerically pure 5'-O-DMT-2'deoxythymidine 3'-O-(S-methyl-methanephosphonothiolate)s and -(Se-methyl-methane-phosphono-selenolate)s by NMR methods are reported. (1)H-(1)H, (1)H-(31)P, and (13)C-(31)P coupling constants and nuclear overhauser enhancement (NOE) connectivities from transverse cross-relaxation experiments in rotating frame (T-ROESY) were measured to correlate the conformational properties of the isomers with the absolute configurations at the phosphorus obtained from X-ray studies of the relatives of S(p) configured isomers. Conformational differences between the stereoisomers were found to be restricted to the different orientation of the C3'-O3'-P bond. The NMR data reflected the preferred epsilon(-) conformation for the S(p) isomers, while in the R(p) isomers the conformational equilibrium was shifted toward the epsilon(t) domain. These results also indicated that for 5'-protected mononucleotides the absolute configuration at the phosphorus atom can be inferred from the NOE experiments and the trends observed in vicinal carbon-phosphorus coupling constants. Copyright 2000 Wiley-Liss, Inc.