Determination of Relative Configuration from Residual Chemical Shift Anisotropy

Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany
Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States
§ Process Research and Development, NMR Structure Elucidation Group, Merck & Co., Inc., 126 E Lincoln Avenue, Rahway, New Jersey 07065, United States
Departamento de Química Fundamental, Universidade Federal de Pernambuco, Cidade Universitária, Recife, PE 50740-560, Brazil
Institute of Organic Chemistry and Institute for Biological Interfaces Karlsruhe, Institute of Technology (KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
J. Am. Chem. Soc., 2016, 138 (30), pp 9548–9556
DOI: 10.1021/jacs.6b04082
Publication Date (Web): June 13, 2016
Copyright © 2016 American Chemical Society


Abstract Image

Determination of relative configuration is frequently a rate-limiting step in the characterization of small organic molecules. Solution NMR-based nuclear Overhauser effect and scalar J-coupling constants can provide useful spatial information but often fail when stereocenters are separated by more than 4–5 Å. Residual dipolar couplings (RDCs) can provide a means of assigning relative configuration without limits of distance between stereocenters. However, sensitivity limits their application. Chemical shift is the most readily measured NMR parameter, and partial molecular alignment can reveal the anisotropic component of the chemical shift tensor, manifested as residual chemical shift anisotropy (RCSA). Hence, 13C RCSAs provide information on the relative orientations of specific structural moieties including nonprotonated carbons and can be used for stereochemical assignment. Herein, we present two robust and sensitive methods to accurately measure and apply 13C RCSAs for stereochemical assignment. The complementary techniques are demonstrated with five molecules representing differing structural classes.

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.6b04082.

  • Experimental details, alignment tensors, RCSA and RDC data for all investigated molecules, a description of gel preparation, derivation of the isotropic shift correction formula, comparison of RCSA data with stretching and compression devices, structural coordinates, and chemical shift tensors (PDF)


Article Views: 702 Times
Received 21 April 2016
Published online 13 June 2016
Published in print 3 August 2016
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