Conformational analysis of an anti-androgenic, (E,E)-8-hydroxygermacrene B, using NOESY and dynamic NMR spectroscopy.

Bioorg Med Chem Lett 2014 Aug 27;24(15):3526-9. Epub 2014 May 27.

Bioscreening Unit, Department of Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmaceutical Sciences and Center of Excellence for Innovation in Chemistry, Naresuan University, Phitsanulok 65000, Thailand. Electronic address:

(E,E)-8-Hydroxygermacrene B was prepared by ketone reduction of germacrone, a naturally occurring compound from Curcuma aeruginosa Roxb. with NaBH4 at low temperature (4 °C). This compound showed remarkable in vitro anti-androgenic activity (IC50 0.15±0.022 mM) applicable to male baldness treatments. NMR analysis at -50 °C indicated that there were four conformational isomers of (E,E)-8-hydroxygermacrene B in a ratio of 48:40:8:4. The major conformers were assigned by (1)H NMR and 2D-NOESY NMR spectroscopy as having methyl groups at C-10 and C-4 in up-down (UD) orientations (48% predominance) and UU (40%). (1)H NMR spectra implied another two minor conformers with these methyls having DU (8%) and DD (4%) orientations.

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http://dx.doi.org/10.1016/j.bmcl.2014.05.057DOI Listing
August 2014
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