Recent developments in the use of one bond C C couplings in structure determination

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The connectivity, conformation, tautomeric form, and dynamics of a new depsidone (perisalazinic acid) were characterized using one-bond 13 C 13 C NMR scalar couplings (1 J CC) obtained from the INADEQUATE experiment. Characterization of perisalazinic acid using more conventional NMR techniques is problematic due to the extremely limited number of C H protons present. In the present study, 81 candidate structures were considered and a best fit structure was selected by comparing computed 1 J CC values for each candidate to 15 experimental values. Of the six flexible moieties in perisalazinic acid, three are adequately represented by a single orientation stabilized by intramolecular hydrogen bonding. The three remaining groups are present as mixtures of conformers with two sites consisting of a pair of conformations and another disordered over six orientations. This study demonstrates the feasibility of complete three-dimensional structural characterization of an unknown using only theoretical and experimental 1 J CC values.

Section: Exploring An Alternative Connectivity In the B-ringsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

NMR structural characterization from one‐bond ¹³C¹³C couplings: Complete assignment of a hydrogen‐poor depsidone

Sestile

Richardson

Toomey

et al. 2020

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“…However, there have been at least five recent reports where a longer range peak has been observed in a 1,1-ADEQUATE spectrum, due to an unusually large two-bond or three-bond 13 C- 13 C coupling constant. [86] Although this possibility cannot be ignored, usually a comparison of HMBC and 1,1-ADEQUATE spectra for the same compound will allow one to determine which of the peaks in the former spectrum are two-bond peaks and which are longer range correlations: critical information for reliable structure elucidation. A 1,1-ADEQUATE spectrum will also include olefinic and aromatic 2 J CH peaks that are often missing from an HMBC spectrum.…”

Section: There Are Significant Ambiguities In the Interpretation Ofmentioning

confidence: 99%

“…[41,88] There are many published examples that illustrate the value of 1,1-ADEQUATE spectra for natural product structure elucidation. [85,86] However, there is a major problem with obtaining a 1,1-ADEQUATE spectrum. Because there is only a ca.…”

Section: Figure 10mentioning

confidence: 99%

“…0.01% probability of adjacent 13 C atoms in a molecule, the sensitivity of a 1,1-ADEQUATE spectrum is very significantly less than that of an HMBC spectrum. Although there have been efforts made to improve the sensitivity of 1,1-ADEQUATE spectra, [86,89] it will still usually not be possible to obtain a 1,1-ADEQUATE spectrum in a reasonable time, unless one has an unusually large amount of sample or access to a cryogenically-cooled probe. When acquiring a 1,1-ADEQUATE spectrum is not possible, it is important to always be aware that the ambiguities in interpreting an HMBC spectrum will often allow for alternative structures that are consistent with the data.…”

Section: Figure 10mentioning

confidence: 99%

See 1 more Smart Citation

Minimizing the risk of deducing wrong natural product structures from NMR data

Burns

Reynolds

2019

There continues to be a disturbing number of natural products reported in the literature whose structures are incorrect. At least in part, this reflects the fact that many natural product chemists have limited formal nuclear magnetic resonance training. Gaps in training and lack of awareness regarding the challenges and ambiguities associated with two‐dimensional nuclear magnetic resonance data interpretation can easily lead to errors in structure elucidation. The purpose of this tutorial is to point out some of these issues, highlight the kinds of errors that have been made and provide specific advice on how to avoid these missteps such that the risk of reporting a wrong structure is minimized.

Computer Assisted Structure Elucidation (CASE): Current and future perspectives

Elyashberg¹,

Argyropoulos²

2020

The first efforts for the development of methods for Computer-Assisted Structure Elucidation (CASE) were published more than 50 years ago. CASE expert systems based on one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) data have matured considerably by now. The structures of a great number of complex natural products have been elucidated and/or revised using such programs. In this article, we discuss the most likely directions in which CASE will evolve. We act on the premise that a synergistic interaction exists between CASE, new NMR experiments, and methods of computational chemistry, which are continuously being improved. The new developments in NMR experiments (long-range correlation experiments, pure-shift methods, coupling constants measurement and prediction, residual dipolar couplings [RDCs]), and residual chemical shift anisotropies [RCSAs], evolution of density functional theory (DFT), and machine learning algorithms will have an influence on CASE systems and vice versa. This is true also for new techniques for chemical analysis (Atomic Force Microscopy [AFM], "crystalline sponge" X-ray analysis, and micro-Electron Diffraction [micro-ED]), which will be used in combination with expert systems. We foresee that CASE will be utilized widely and become a routine tool for NMR spectroscopists and analysts in academic and industrial laboratories. We believe that the "golden age" of CASE is still in the future.