Reassignments and Corroborations of Oxo‐Bridged Natural Products Directed by OSE and DU8+ NMR Computation

Abstract

Structural misassignments of natural products are prevalent in the literature. Developing methods and theoretical concepts to assist those undertaking structural elucidation is therefore of paramount importance, such that biologists and synthetic chemists avoid pursuing phantom chemical entities. Herein described is a strategy for predicting the isolabilities of oxygen‐substituted bridgehead natural products based on calculations of olefin strain energies, NMR chemical shifts and coupling constants (DU8+). This approach provides corroborating evidence for the structures of certain bridgehead alkene natural products while leading to the reassignment of several other structures.

The DP5 Probability, Quantification and Visualisation of Structural Uncertainty in Single Molecules

“…Not only are the correct and incorrect structures almost indistinguishable to an expert chemist, these structures have already been incorrectly assigned and revised in the literature. 1,[34][35][36][37][38] The results of this study are striking and are presented in Figure 6. In all cases the DP5 probabilities of the incorrect structures are equal to or close to one, illustrating that DP5 can reliably pick out even the most subtle inconsistencies in molecular structures.…”

“…1 Many of these incorrectly assigned are only discovered after costly and time consuming total syntheses are completed revealing a discrepancy between the experimental and literature NMR data. 2,34 Over the last two decades, many computational tools have been developed to aid the assignment of NMR spectra and elucidation of molecular structures. [5][6][7] Comparing experimental NMR shifts with those calculated for a candidate structure using density functional theory (DFT) is now a well-established methodology and has been used to solve the structures of many molecules.…”

The DP5 Probability, Quantification and Visualisation of Structural Uncertainty in Single Molecules

“…To further test the efficacy of DP5 analysis, the system was evaluated against thirteen real-world examples of structures originally incorrectly published in the literature and later reassigned, these structures are presented in Figure 5. 1,55,[58][59][60][61][62] The results of this study are striking and are presented in Figure 6. In all cases the DP5 probabilities of the incorrect structures are equal to or close to zero, illustrating that DP5 can reliably pick out even the most subtle inconsistencies in molecular structures.…”

The DP5 Probability, Quantification and Visualisation of Structural Uncertainty in Single Molecules

“…To further test the efficacy of DP5 analysis, the system was evaluated against thirteen real-world examples of structures originally incorrectly published in the literature and later reassigned, these structures are presented in Figure 5. 1,58,[61][62][63][64][65] The results of this study are striking and are presented in Figure 6. In all cases the DP5 probabilities of the incorrect structures are equal to or close to zero.…”