Computer-Assisted 3D Structure Elucidation (CASE-3D): The Structural Value of ² J_CH in Addition to ³ J_CH Coupling...

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.