Assignment of Relative Configuration of Desoxypropionates by super(1)HNMR Spectroscopy: Method Development, Proof of Principle by Asymmetric Total Synthesis of Xylarinic Acid A and Applications

• Published in: Chemistry : a European journal Vol. 18; no. 23; pp. 7071 - 7081
• Main Authors: Schmidt, Yvonne, Lehr, Konrad, Colas, Lucie, Breit, Bernhard
• Format: Journal Article
• Language: English
• Published: 01.06.2012
• Subjects: Asymmetry; Natural products; Nuclear magnetic resonance; Solvents; Spectra; Spectroscopy; Synthesis; Trends
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201103988

The determination of the relative configuration of 1,3-dimethyl-substituted alkyl chains is possible by interpretation of super(1)HNMR shift differences. Additionally, assignments are feasible in a variety of deuterated solvents, because the corresponding shift differences are not significantly influenced by the solvent. The trends for Delta delta values depending on functional groups adjacent to the stereogenic centers are shown. Based on a thorough comparison with literature data, the relative configuration of natural products can be predicted. For this purpose, we derived an empirical rule for the ranges in which Delta delta values usually occur. Furthermore, we were able to proof the validity of our method by the successful prediction of the relative configuration for the polyketide natural product xylarinic acid A, which was confirmed by the asymmetric total synthesis of its enantiomer. Based on the proposed simple analysis of published super(1)HNMR data and the determination of the relevant chemical-shift differences, we predicted the relative configurations of several previously unassigned natural products. Unraveling the unknown: Interpretation of methylene-proton NMR signals of 1,3-dimethyl-substituted alkyl chains allows for the assignment of the relative configuration of the two adjacent stereogenic centers (see figure). The new method is applicable in various NMR solvents and general trends and rules for assignment are shown. Natural products with unknown configuration can be assigned by using the information gained from already published spectra.