Computer‐Assisted 3D Structure Elucidation (CASE‐3D): The Structural Value of <sup>2</sup><i>J</i><sub>CH</sub> in Addition to <sup>3</sup><i>J</i><sub>CH</sub> Coupling Constants
Martin R. M. Koos, Armando Navarro‐Vázquez, Clemens Anklin, Roberto R. Gil
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.