Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• between plakilactone G and plakilactone H allowed us to determine the absolute configuration in this two new oxygenated polyketides. Keywords: chemical shift calculations; DFT; NMR spectroscopy; quantitative NOE; stereochemical determination of flexible systems; Introduction In recent years the quantum

• due to equilibriums between multiple conformers, which are present in highly flexible molecules. Recently, the quantitative NOE-based method has been extended to relatively flexible compounds, and the reliability of the approach for the analysis of multiconformational systems was shown [19][20]. Due

• to the huge chemical variety of secondary metabolites from natural sources, the identification of the configuration of highly flexible compounds is still a great challenge. We recently demonstrated that an integrated approach combining quantitative NOE-based protocol in parallel with the quantum

Accuracy in determining interproton distances using Nuclear Overhauser Effect data from a flexible molecule

• Catharine R. Jones,
• Craig P. Butts and
• Jeremy N. Harvey

Beilstein J. Org. Chem. 2011, 7, 145–150, doi:10.3762/bjoc.7.20

• multi-conformer, flexible small molecules was investigated with the model compound 4-propylaniline. The low accuracy assumed for semi-quantitative NOE distance restraints is typically taken to suggest that large numbers of constraints need to be used in the dynamical analysis of flexible molecules, and

• experimental results are consistent with a population of 1a/b lying in the range 40 to 65%. However, typical semi-quantitative NOE studies are assumed to lead to much larger errors in distances, in the order of ± 10% (red line in Figure 2), or even assign distance-ranges to NOE intensities such as strong (2–3

• molecules. The high accuracy of this distance data allows it to be applied to assessing/confirming the relative populations of contributing conformers in small, flexible molecules with reasonable certainty, even where very few restraints are available – succeeding where traditional semi-quantitative NOE