Neue Materialien und Strategien für NMR basierte Strukturbestimmung organischer Moleküle
Zusammenfassung der Projektergebnisse
The goal of this DFG/CAPES joint project was to develop new materials and strategies for NMR-based structural elucidation of organic compounds. Generally, we have achieved the following goals: (1) With the synthesis of an aspartic acid-derived polyarylacetylene, the synthesis of a DMSO-compatible chiral alignment medium was achieved. (2) The synthesis of two almost completely deuterated helically-chiral polyacetylenes and the demonstration of their usability as alignment media for very small amounts of analytes was achieved. (3) Methods for the residual chemical shift anisotropy (RCSA) based enantiodifferentiation in polyacetylene liquid crystal have been established. (4) By using helically-chiral polyacetylenes with dipeptide-like side chains, the dominant role of the helical chirality in enantiodifferentiation by chiral lyotropic liquid crystalline phases was demonstrated. This result is also supported by experiments with copolymers (statistical and block) of polyisonitriles. (5) Cross-linking polymerization of polysiloxane diynes with valine-derived 4-ethynylbenzamides allowed the preparation of swellable gels. These exhibited good enantiodifferentiation toward chiral analytes and were characterized by a strong dependence of analyte orientation on temperature. This property can be exploited to measure multi-alignment data sets. (6) The computer program ConArch+, developed in 2018, has been significantly enhanced. Starting from an arbitrary initial configuration, any number of data sets (anisotropic and isotropic NMR parameters) can be used simultaneously for automated determination of relative configurations and conformations of chiral compounds with more than one stereogenic element. Furthermore, it could be shown that principally unavoidable uncertainties concerning the atomic positions in calculated structures fundamentally question the validity of the common structure verification-falsification method. (7) A novel method has been introduced and established for measuring RCSA data using oligopeptidebased LLC phases. This approach facilitates the efficient acquisition of high-quality RCSA data through a straightforward process, eliminating the requirement for specialized instrumentation and NMR tubes. (8) The relative and absolute configuration of several challenging novel natural products have been determined using anisotropic NMR analysis. (9) New alignment media based on the molecular self-assembly of oligopeptide amphiphile (OPA) have been proposed. These media exhibit compatibility with diverse solvent systems, and their amino acid sequences can be easily adjusted. This adjustability enables the acquisition of independent anisotropic NMR datasets. (10) Demonstrations of strategies for predicting anisotropic NMR data through atomistic MD simulations have been showcased. These demonstrations pave the way for a new approach to assigning absolute configurations based on anisotropic NMR data acquired within chiral alignment media.
Projektbezogene Publikationen (Auswahl)
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2H and 13C NMR‐Based Enantiodetection Using Polyacetylene versus Polypeptide Aligning Media: Versatile and Complementary Tools for Chemists. ChemPlusChem, 84(2), 144-153.
Lesot, Philippe; Berdagué, Philippe; Meddour, Abdelkrim; Kreiter, Alexander; Noll, Markus & Reggelin, Michael
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Stereochemical Elucidation of Natural Products from Residual Chemical Shift Anisotropies in a Liquid Crystalline Phase. Journal of the American Chemical Society, 142(5), 2301-2309.
Li, Xiao-Lu; Chi, Lu-Ping; Navarro-Vázquez, Armando; Hwang, Songhwan; Schmieder, Peter; Li, Xiao-Ming; Li, Xin; Yang, Sui-Qun; Lei, Xinxiang; Wang, Bin-Gui & Sun, Han
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Configurational Analysis by Residual Dipolar Couplings: Critical Assessment of “Structural Noise” from Thermal Vibrations. Angewandte Chemie International Edition, 60(7), 3412-3416.
Reggelin, Michael & Immel, Stefan
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Magnetically Induced Alignment of Natural Products for Stereochemical Structure Determination via NMR. Angewandte Chemie International Edition, 59(37), 15860-15864.
Karschin, Niels; Wolkenstein, Klaus & Griesinger, Christian
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Relative configuration of micrograms of natural compounds using proton residual chemical shift anisotropy. Nature Communications, 11(1).
Nath, Nilamoni; Fuentes-Monteverde, Juan Carlos; Pech-Puch, Dawrin; Rodríguez, Jaime; Jiménez, Carlos; Noll, Markus; Kreiter, Alexander; Reggelin, Michael; Navarro-Vázquez, Armando & Griesinger, Christian
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Bayesian Inference Applied to NMR-Based Configurational Assignments by Floating Chirality Distance Geometry Calculations. Journal of the American Chemical Society, 144(15), 6830-6838.
Immel, Stefan; Köck, Matthias & Reggelin, Michael
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Poly(arylisocyanides) as Versatile, Enantiodiscriminating Alignment Media for Small Molecules. ChemPlusChem, 87(1).
Wesp, Svenja; Wolf, Kai; Immel, Stefan & Reggelin, Michael
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Weizhouochrones: Gorgonian-Derived Symmetric Dimers and Their Structure Elucidation Using Anisotropic NMR Combined with DP4+ Probability and CASE-3D. Journal of Natural Products, 85(7), 1730-1737.
Li, Xiao-Lu; Ru, Tong; Navarro-Vázquez, Armando; Lindemann, Peter; Nazaré, Marc; Li, Xu-Wen; Guo, Yue-Wei & Sun, Han
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Residual‐Chemical‐Shift‐Anisotropy‐Based Enantiodifferentiation in Lyotropic Liquid Crystalline Phases Based on Helically Chiral Polyacetylenes. Angewandte Chemie International Edition, 62(46).
Fuentes‐Monteverde, Juan Carlos; Noll, Markus; Das, Akhi; Immel, Stefan; Reggelin, Michael; Griesinger, Christian & Nath, Nilamoni
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Absolute Configuration of 12S-Deoxynortryptoquivaline from Ascidian-Derived Fungus Aspergillus clavatus Determined by Anisotropic NMR and Chiroptical Spectroscopy. Journal of Natural Products, 87(2), 381-387.
Doro-Goldsmith, Elisa; Song, Qi; Li, Xiao-Lu; Li, Xiao-Ming; Hu, Xue-Yi; Li, Hong-Lei; Liu, Hao-Ran; Wang, Bin-Gui & Sun, Han
