Using DP4+ probability for structure elucidation of sesquiterpenic lactones: The case of (−)‐Istanbulin A

Theoretical calculations have become a crucial support for experimental data when it comes to confirming and/or rejecting molecular structure. Quantum calculations have therefore become essential for other research fields, such as total synthesis of natural products or the study of their mechanisms of action, among others. In this communication, four different parameters are used for the confirmation of the structure of (−)‐Istanbulin A, testing the experimental NMR data against eight possible stereoisomers. (−)‐Istanbulin A is a natural product (an eremophilane) extracted from the aerial parts of Senecio filaginoides DC (an endemic plant from Patagonia Argentina) that has proven successful as antibacterial and antifungal agent. The structures of the eight possible stereoisomers were optimized by means of DFT calculations (B3LYP/6‐311+G[d,p] in vacuum), and then their isotropic shielding tensors were obtained using GIAO‐B3LYP/6‐31+G(d,p) method in chloroform. Isotropic shielding values of 1H and 13C were converted into chemical shifts by subtraction of TMS analog values. The eight sets of calculated data were compared with the spectroscopic chemical shifts in order to find the most probable structure. This was made by means of the parameters R2 (correlation coefficient), MAE (mean absolute error), CMAE (corrected mean absolute error), and DP4+ probability. While R2, MAE, and CMAE afford uncertain results which do not permit confirmation of the molecular structure, DP4+ predicts the isomer of configuration (4S,5R,8R,10S) with more than 99% probability. These results open the possibility of applying DP4+ method for confirming the relative configuration of other istanbulins (and probably other eremophilanes).