Submitted to: Journal of Natural Products
Publication Type: Peer reviewed journal
Publication Acceptance Date: 1/6/2009
Publication Date: 3/5/2009
Citation: Walse, S.S., Wang, B., Dossey, A.T., Edison, A.S., Merz, K.M. 2009. Relative Configuration of Natural Products Using NMR Chemical Shifts. Journal of Natural Products. 72(4):709-713. Interpretive Summary: Nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for natural product discovery, as it can be used to probe a variety of important structural features of chemical compounds. Some NMR techniques, such as those that target covalent connectivity, are well developed. Determining the relative configuration of atoms in chemical compounds, on the other hand, is frequently a difficult task with NMR. This work demonstrates the power of using theoretical calculations based on quantum chemistry to extract the valuable information contained in NMR chemical shifts and thus provides a novel approach to assign the relative stereochemistry of natural products.
Technical Abstract: By comparing calculated with experimental NMR chemical shifts, we were able to determine the relative configurations of three monoterpene diastereomers produced by the walkingstick Anisomorpha buprestoides. The combined RMSDs of both 1H and 13C quantum chemically calculated shifts were able to predict the correct isomer, especially when only aliphatic nuclei were used. The calculated relative energies and interproton distances were also consistent with chemical isomerization experiments and NOE based interproton distance calculations. The combination of calculated and experimental NMR chemical shifts provides an accurate and efficient method to assign the relative configuration of natural products.