Determination of Relative Configuration from Residual Chemical Shift Anisotropy.
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, (13)C 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 (13)C RCSAs for stereochemical assignment. The complementary techniques are demonstrated with five molecules representing differing structural classes.
Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry , 37077 Göttingen, Germany.
Nilamoni
N
Nath
Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry , 37077 Göttingen, Germany.
Manuel
M
Schmidt
Department of Chemistry, Carnegie Mellon University , 4400 Fifth Avenue, Pittsburgh, Pennsylvania 15213, United States.
Roberto R
RR
Gil
Process Research and Development, NMR Structure Elucidation Group, Merck & Co., Inc. , 126 E Lincoln Avenue, Rahway, New Jersey 07065, United States.
R Thomas
RT
Williamson
Process Research and Development, NMR Structure Elucidation Group, Merck & Co., Inc. , 126 E Lincoln Avenue, Rahway, New Jersey 07065, United States.
Gary E
GE
Martin
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.
Armando
A
Navarro-Vázquez
Department of NMR-based Structural Biology, Max Planck Institute for Biophysical Chemistry , 37077 Göttingen, Germany.
Christian
C
Griesinger
Process Research and Development, NMR Structure Elucidation Group, Merck & Co., Inc. , 126 E Lincoln Avenue, Rahway, New Jersey 07065, United States.
Yizhou
Y
Liu