Absolute Configuration of Eremophilane Sesquiterpenes from Petasites hybridus: Comparison of Experimental and Calculated Circular Dichroism Spectra

In-depth conformational analyses of 10 known eremophilane (= (IS,4a-R,7R,8aR)-decahydro-1,8a-dimethyl-7-(1-methylethyl)napththalene) sesquiterpenes,.1-10, from Petasites hybridus were performed with molecular mechanics as well as density functional theory methods. Electronic transition energies and rotational strengths of these eight eremophilane lactones and two petasins were calculated by time-dependent density functional theory (B3PW91/TZVP). The absolute configurations of the constituents could be assigned by comparison of their simulated and experimental circular dichroism (CD) spectra in methanol as (4S,5R,8S,10R) (1, 2), (2R,4S,5R,8S,10R) (3, 4, 5), (2R,4S,5R,8R,9R,10R) (6), (2R,4S,5R,8R,10R) (7, 8), and (3R,4R,5R) (9, 10). Single-crystal X-ray diffraction data of 8p-hydroxyeremophilanolide ((8S)-8-hydroxyeremophil-7(11)-en-12,8-olide) (1) served as starting point for the theoretical conformational calculations of the 8 beta-epimers of the eremophilane lactones. Experimental CD spectra as well as H-1 NMR spectra of compound 1 in methanol were considerably dependent on sample concentration. Chirality 22:308-319, 2010. (C) 2009 Wiley-Liss, Inc.