GABAergic phthalide dimers from Angelica sinensis (Oliv.) diels

The methanol extract of Angelica sinensis (Oliv.) Diels roots (Dang Gui) has been shown to exhibit competitive binding to the GABAa receptor, suggesting the presence of GABAergic ligands. Chromatographic fractionation of the methanol extract led to the isolation of two GABAergic dimeric plithalides 1 and 2. Gelispirolide (1) was elucidated as a new plithalide dimer composed of a Z-figustilide and a Z-butylidenephthalide unit on the basis of spectroscopic approaches including one- and two-dimensional NMR, HRESIMS and HRESIMS-MS. Compound 2 was identified as the known dimeric plithalide, riligustilide, by comparison of its spectroscopic data with literature values. Its dimeric linkage and stereochemistry were ascertained by a single crystal X-ray diffraction experiment. Both dimers 1 and 2 were found to be active in an in vitro GABAa receptor-binding assay with IC50 values of 29 and 24 mu m, respectively. Copyright (c) 2006 John Wiley & Sons, Ltd.