NOESY and DFT-GIAO Calculations Reveal Pervasive Errors in C20 Configurations of Taraxastane-3,20-diols: Proposals to Improve NMR Structure Determinations

Abstract

The current scientific consensus generally assigns incorrect C20 configurations to taraxastane-3β,20-diols and their oxo derivatives reported in 32 articles. Definitive configurations established here by NOESY, quantum mechanical NMR predictions, and 13 C NMR γ-gauche effects warrant updating of the many erroneous structures. Suggestions to improve NMR structure determinations of such nonpolar polycyclic natural products include acquiring 2D spectra at higher resolution, suppressing zero-quantum coherence in NOESY, and judging proposed NOE correlations against H−H distances. * sı Supporting InformationThe Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.orglett.9b04566.Experimental methods, isolation of 1−3, GC-MS and NMR spectra, NMR tables, NOESY integrals, DFT-GIAO NMR calculations, and the code for the t1away program (PDF) Raw_nmr_data.zip (ZIP)

An ECD and NMR/DP4+ Computational Pipeline for Structure Revision and Elucidation of Diphenazine-Based Natural Products

“…16,17 In particular, the calculation of 1 H and 13 C NMR data using density functional theory (DFT) has been recently proven to be a reliable tool for the structural revision of natural products. 18,19 The development of DP4 and DP4+ probability measures by Goodman and Sarotti further enabled the statistical comparison between calculated and experimental NMR data. 20,21 In this study, we developed a computational pipeline using ECD and gauge-independent atomic orbital (GIAO) NMR shift calculations coupled with a DP4+ probability measure to determine the relative and absolute configurations as well as phenol positions of diphenazine-based natural products.…”

“…Computational analyses of spectroscopic data, such as optical rotation dispersion (ORD), electronic circular dichroism (ECD), and NMR, have been widely used for the structure characterization of complex natural products. , In particular, the calculation of 1 H and 13 C NMR data using density functional theory (DFT) has been recently proven to be a reliable tool for the structural revision of natural products. , The development of DP4 and DP4+ probability measures by Goodman and Sarotti further enabled the statistical comparison between calculated and experimental NMR data. , In this study, we developed a computational pipeline using ECD and gauge-independent atomic orbital (GIAO) NMR shift calculations coupled with a DP4+ probability measure to determine the relative and absolute configurations as well as phenol positions of diphenazine-based natural products. Using this pipeline, we propose the structure revision of molecules isolated from our efforts, phenazinolin D ( 4 ), izumiphenazine A ( 5 ), and baraphenazine G ( 7 ) .…”

Penitol A and Penicitols E–I: Citrinin Derivatives from Penicillium citrinum and the Structure Revision of Previously Proposed Analogues

“…For this type of citrinin derivative, penicitols A ( 7 ) and E–I ( 2 – 6 ), differences of interatomic distances between H-1 and H-14 for syn- and anti- configurations are small, which leads to NOESY and 1D NOE signals being ambiguous . In this study, the X-ray diffraction analysis proves that the DP4+ analysis based on DFT-GIAO calculations is appropriate for the stereochemical assignment of these compounds, which have close interatomic distances (<3 Å) of vicinal hydrogens.…”

Combining Desferriferrioxamine B and 1‐Hydroxy‐2‐Piperidone ((PIPO)H) to Chelate Zirconium. Solution Structure of a Model Complex of the [89Zr]Zr−DFOcyclo*−mAb Radioimmunoconjugate

“…This code allows the reader to notice that most of the distances are <3.0 Å. We make an inventory of the distances 4.0 < d <5.0 Å, as this range includes the upper distance limit to account for the relatively intense (0.50–0.67) corresponding rOe cross‐peaks [28] . All the nine structures listed in Table 1 include at least one and at most three distances 4.0 < d <5.0 Å, which involve the proton pairs {5a‐H, 7‐H}, {10b‐H, 13a‐H}, and {28ab‐H, 31‐H} in most cases, and {7‐H, 9‐H} in one case.…”