C <i>i</i> SE: Chirality In Silico Structure Elucidation for Stereochemical Assignment of Natural and Synthetic Organic Compounds

Stereochemical elucidation of synthetic and natural compounds is a rate-determining step in the structure determination process. In the present work, we introduce a method called Chirality In Silico Structure Elucidation (CiSE), which employs ¹J_CC coupling constants to determine the correct stereochemistry of natural products. To determine the correct stereochemistry, the proposed method assigns a probability to all possible structures of a compound in question. For calculating these probabilities, the errors between the experimental and density functional theory (DFT) computed ¹J_CC couplings of a large number of compounds are fitted into Student's t-distribution, from which statistical parameters such as mean, standard deviation, and degrees of freedom are determined. Afterward, the probabilities for all possible candidate structures are calculated using Bayes's theorem, with the correctly assigned stereoisomer typically exhibiting a probability exceeding 95%.