Assignment of relative configuration to acyclic compounds based on C-13 NMR shifts. A density functional and molecular mechanics study

1,3-Dimethylated hydrocarbon segments occur frequently as structural elements in polyketide natural products. The C-13 NMR chemical shifts of a series of model compounds containing such segments can be well reproduced by a combination of molecular mechanics and SOS-DFPT/IGLO calculations. C-13 NMR chemical shifts are calculated on MM3 geometries and are Boltzmann weighted according to the MM3 energies. On the basis of the resulting thermally averaged chemical shifts, all diastereomers of the model compounds can be unequivocally distinguished. Significant differences in chemical shifts occur at methyl groups and methylene groups that are adjacent to a single stereogenic center. The method is applied to predict the relative configuration of two stereocenters in the side chains of two natural products, sambutoxin and the bradykinin inhibitor L-755,897.