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

摘要

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.