Using DP4+ probability for structure elucidation of sesquiterpenic lactones: The case of (−)‐Istanbulin A. (28th August 2021)

• Record Type: Journal Article
• Authors: Colasurdo, Diego D.; Arancibia, Luz A.; Naspi, Mariana L.; Laurella, Sergio L.
• Is Part Of: Journal of physical organic chemistry. Volume 35:Number 1(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-08-28
• Subjects: eremophilane -- Istanbulin -- nuclear magnetic resonance -- theoretical calculations; Chemistry, Physical organic -- Periodicals; 547.1
• DOI: 10.1002/poc.4282
• Languages: English
• ISSNs: 0894-3230

Abstract

Abstract: 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 1 H and 13 C 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 R 2 (correlation coefficient), MAE (mean absolute error), CMAE (corrected mean absolute error), and DP4+ probability. While R 2, 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). Abstract : (−)‐Istanbulin A is a natural product (an eremophilane) extracted from Senecio filaginoides DC (Patagonia Argentina), a promising antibacterial and antifungal agent. The theoretical NMR chemical shifts of eight possible stereoisomers were calculated using GIAO‐B3LYP/6‐31+G(d, p) method in chloroform. They were compared to experimental chemical shifts by means of four parameters R 2 (correlation coefficient), MAE (mean absolute error), CMAE (corrected mean absolute error) and DP4+ probability. R 2, MAE, and CMAE afford uncertain results. DP4+ predicts the isomer (4S, 5R, 8R, 10S) with 99.9% probability.