Beyond DP4: an Improved Probability for the Stereochemical Assignment of Isomeric Compounds using Quantum Chemical Calculations of NMR Shifts

Abstract

The DP4 probability is one of the most sophisticated and popular approaches for the stereochemical assignment of organic molecules using GIAO NMR chemical shift calculations when only one set of experimental data is available. In order to improve the performance of the method, we have developed a modified probability (DP4+), whose main differences from the original DP4 are the inclusion of unscaled data and the use of higher levels of theory for the NMR calculation procedure. With these modifications, a significant improvement in the overall performance was achieved, providing accurate and confident results in establishing the stereochemistry of 48 challenging isomeric compounds.

PPAR Modulating Polyketides from a Chinese Plakortis simplex and Clues on the Origin of Their Chemodiversity

“…were 1.71 for 15b vs 2.97 for 15a]. The two possible diastereomers were also compared by using the recent DP4+ probability method 25 and, also in this case, structure 15b resulted the most likely (see Supporting Information). On the basis of these computational data, the relative configuration of 15b was suggested for plakdiepoxide.…”

Verbenanone, an octahydro-5 H -chromen-5-one from a Hawaiian-plant associated fungus FT431

“…For instance, the CMAE values of isomers 2-32 ranged 1.5–3.7 ppm ( 13 C) and 0.09–0.29 ppm ( 1 H), higher than those computed for isomer 1 (1.3 ppm and 0.09 ppm, respectively), showing higher CMaxErr values as well (3.0–12.2 ppm for carbon data, 0.21–0.99 ppm for proton data). With this data in hand, we finally computed the DP4+ probability, 16 among the preferred strategies to assess the most likely structure when only one set of experimental data is available. 14,16 As expected, the DP4+ values strongly suggested isomer 1 as the correct candidate in high confidence (>99.9%).…”

Chemistry and Selective Tumor Cell Growth Inhibitory Activity of Polyketides from the South China Sea Sponge Plakortis sp.

“…Although mean absolute errors (MAE) values of 1 H NMR and 13 C NMR were not in accordance, 13 C NMR MAE values clearly pointed out 1a as the most probable isomer (MAE values: 1.83 for 1a , 2.14 for 1b ) (Figure 5). To unambiguously assign the relative configuration of 1 , we then computed the DP4+ probabilities [42] (Table 2) for the two possible considered stereoisomers ( 1a - 1b ). Specifically, the best DP4+ performance in predicting the correct stereochemistry of organic compounds has been associated to the combination of both 1 H and 13 C chemical shift data.…”