Structural Discrimination in Small Molecules by Accurate Measurement of Long-Range Proton–Carbon NMR Residual Dipolar Couplings

Authors

  • Pablo Trigo-Mouriño,

    1. Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave, Pittsburgh, PA 15213 (USA)
    2. Departamento de Química Orgánica, Universidade de Vigo, 36310 Vigo (Spain)
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  • Armando Navarro-Vázquez,

    1. Departamento de Química Orgánica, Universidade de Vigo, 36310 Vigo (Spain)
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  • Jinfa Ying,

    1. Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (USA)
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  • Roberto R. Gil,

    Corresponding author
    1. Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave, Pittsburgh, PA 15213 (USA)
    • Department of Chemistry, Carnegie Mellon University, 4400 Fifth Ave, Pittsburgh, PA 15213 (USA)
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  • Ad Bax

    Corresponding author
    1. Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (USA)
    • Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 (USA)
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  • NMR instrumentation at CMU is partially supported by the NSF (CHE-0130903). A.N. thanks Centro de Supercomputación de Galicia (CESGA) for computer time, Xunta de Galicia/FEDER (Consellería de Educación 2009/071) for financial support, the Spanish Government for a research grant (CTQ2007-65310), and a “Ramón y Cajal” research contract. We thank Dr. N. V. Tsarevsky from Southern Methodist University (Dallas, TX) for PMMA gels and Dr. V. E. Nicotra from Córdoba National University (Córdoba, Argentina) for the authentic sample of 10-epi (1). This work was supported by the Intramural Research Program of the NIDDK, the NIH, and the Intramural AIDS-Targeted Antiviral Program of the Office of the Director, NIH.

Abstract

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Accurate measurement of long-range CH residual dipolar couplings (RDCs; 2DCH and 3DCH) by a new selective J-scaled HSQC experiment significantly improves the structural discrimination power of RDCs in small molecules with multiple stereogenic centers. The current approach was demonstrated with 10-epi-8-deoxycumambrin B, a tricyclic natural compound with five stereogenic centers (see figure; SVD=singular value decomposition).

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