Computer‐Assisted 3D Structure Elucidation (CASE‐3D): The Structural Value of 2JCH in Addition to 3JCH Coupling Constants. Issue 10 (30th January 2020)

• Record Type: Journal Article
• Authors: Koos, Martin R. M.; Navarro‐Vázquez, Armando; Anklin, Clemens; Gil, Roberto R.
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 10(2020)
• Page Start: 3938
• Page End: 3941
• Publication Date: 2020-01-30
• Subjects: CASE-3D -- configuration determination -- HSQMCB -- long-range J coupling -- structure elucidation; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201915103
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: We present a method to use long‐range CH coupling constants to derive the correct diastereoisomer from the molecular constitution of small molecules. A set of 79 2 J CH and 3 J CH values collected from a single HSQMBC experiment on a sample of strychnine were used in the CASE‐3D (computer‐assisted 3D structure elucidation) protocol. In addition to the most commonly used 3 J CH coupling constants, the subset of 32 2 J CH values alone showed an excellent degree of configuration selection. The study is mainly based on comparison of DFT‐calculated 2, 3 J CH values with experimental ones, critical for the case of 2 J CH . But the configuration selection also works well using 3 J CH values predicted from a semi‐empirical Karplus‐based equation limited to H−C−C−C fragments. The robustness, shown using strychnine as a proof of concept, makes the J ‐based CASE‐3D analysis a viable option for the application in fields such as peptide and carbohydrate research, organic synthesis, natural‐product identification and analysis, as well as medicinal chemistry. Abstract : Tying up loose ends : New NMR pulse sequences allow J ‐coupling measurement between remote nuclei. Combined with computationally cheap but sufficiently accurate DFT calculations, CASE‐3D, a simple and automatable protocol for structure selection, shows the discriminatory power of long‐range CH coupling interactions.