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

Stereochemical characterization of diastereomerically pure 5'-O-DMT-2'deoxy thymidine 3'-O-(S-methyl-methanephosphonothiolate)s and -(Se-methylmethane- phosphono-selenolate) s by NMR methods are reported. H-1-H-1, H-1-P-31, and C-13-P-31 coupling constants and nuclear overhauser enhancement (NOE) conn ectivities from transverse cross-relaxation experiments in rotating frame ( T-ROESY) were measured to correlate the conformational properties of the is omers with the absolute con figurations at the phosphorus obtained from X-r ay studies of the relatives of S-p configured isomers. Conformational diffe rences between the stereoisomers were found to be restricted to the differe nt 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 c onformational equilibrium was shifted toward the epsilon(L) domain. These r esults also indicated that for 5'-protected mononucleotides the absolute co nfiguration at the phosphorus atom can be inferred from the NOE experiments and the trends observed in vicinal carbon-phosphorus coupling constants. C hirality 12:675-680, 2000. (C) 2000 Wiley-Liss, Inc.