Quantum Mechanical Calculation of NMR Parameters in the Stereostructural Determination of Natural Products

Abstract

The present microreview highlights the recent goals reached by the application of a combined approach of NMR spectroscopy and quantum chemical methods in the structural studies of natural products. In particular, different case studies are reported, showing the comparison of calculated NMR parameters at the quantum mechanical (QM) theory level with experimental data for the configurational assignment of organic compounds. Moreover, it is shown that the QM-NMR

Addressing the Stereochemistry of Complex Organic Molecules by Density Functional Theory-NMR: Vannusal B in Retrospective

“…Intercepts and slopes of the fitting lines are very similar to what is generally observed for 13 C chemical shift correlations using DFT protocols. 4-9 The R 2 coefficient is quite instructive: when the correlation is done with respect to the experimental values of that particular structure R 2 is well above 0.98, confirming the generally good performance of the DFT protocol. In contrast, when the calculated values are correlated with the experimental values of vannusal B the quality of the correlation is much lower (except, obviously, for 5-2 which is the true structure of vannusal B), indicating that the computational protocol is capable of distinguishing among the different vannusal structures.…”

“…The results were then evaluated in terms of the maximum absolute error MaxErr and the corrected mean absolute error (CMAE). 4a,9 Both parameters are calculated with respect to the value predicted by the linear fit rather than to the experimental value, so as to avoid the possible bias introduced by a systematic error in the correlation, e.g. caused by an inaccurate evaluation of the reference shielding.…”

STRUCTURAL REASSIGNMENT OF EPIERYTHRATIDINE, AN ALKALOID FROM Erythrinafusca, BASED ON NMR STUDIES AND COMPUTATIONAL METHODS

“…[10][11][12] These methods have been very important, together with total synthesis, 13 to determine the structures of unusual natural substances, 14,15 and differentiate diastereoisomers, 16 through calculations of proton-proton and proton-carbon J coupling constants as a tool for the assignment of the relative configurations of chiral organic compounds, an approach that agrees very well with the experimental data. [17][18] Moreover, extensive spectroscopic analyses and quantum mechanical (QM) methods have been used for the reassignment of some structures, 19 and can be very helpful to confirm both rigid and flexible molecular scaffolds.…”

Toward Closing the Gap: Quantum Mechanical Calculations and Experimentally Measured Chemical Shifts of a Microcrystalline Lectin

“…9, 23–26 DFT calculations are accurate enough to yield good agreements between chemical shift and molecular structure for medium-sized molecules, 27–28 and have also been explored for protein structure validation and refinement. 23, 29 While this approach has been rarely used for proteins in the past, given the associated computational demands, it currently is starting to gain momentum due to the rapidly increasing availability of sufficiently powerful computational resources and robust software.…”