25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

New approaches for J-coupling measurement and five-membered ring conformation analysis

27 Aug 2019, 16:15
Lecture Hall B (Henry Ford Building)

Lecture Hall B

Henry Ford Building

Invited talk Small molecules Small Molecules


Dr Davy Sinnaeve (CNRS / Université de Lille)


For any conformational analysis based on spectroscopic data, both the amount of data extracted and the accuracy of the theoretical relation between data and conformation are key. In this presentation, new developments for both the measurement of 1H-1H J-couplings and their use for conformational analysis of five-membered rings will be discussed.
Measuring J-couplings in compounds that are mostly aliphatic can be problematic, as the limited chemical shift dispersion and the presence of many couplings often results in intricate and overlapping multiplets. Also strong coupling conditions are common, which complicates accurate J-coupling extractions. A number of strategies will be presented that build on the PSYCHEDELIC experiment [1] that can resolve these issues.
Five-membered rings are widely occurring in biological and synthetic compounds, and the preferred ring conformation is often crucial for function. In contrast to six-membered rings, five-membered rings are generally flexible, sampling a distribution of conformers, making their analysis challenging. Experimentally, vicinal J-couplings are ideal for conformational analysis of ring systems, as they are sensitive to dihedral angles. However, a key issue is that the available Karplus relations are not always appropriate for a given system. For instance, for difluorinated prolines [2,3], existing Karplus relations for 1H-1H couplings turn out to be insufficently accurate, while no appropriate relations exist for 1H-19F couplings. Also non-bonded electronic interactions across the five-membered ring have significant impact on the J-coupling. We therefore resorted to an alternative approach that is based on extensive mapping of the full conformational space of model compounds using DFT, followed by J-coupling calculation.
[1] Sinnaeve D. et al., Angew. Angew. Chem. Int. Edit. (2016), 55, 1090
[2] Hofman G.J. et al., Chem. Commun. (2018), 54, 5118
[3] Hofman G.J. et al., J. Org. Chem. (2019), 84, 3100

Primary author

Dr Davy Sinnaeve (CNRS / Université de Lille)

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