Furofuranone Lignans from Leucophyllum ambiguum

Eight furofuranone lignans with an endo,endo relationship between the oxygen atoms, an exo,exo relationship between the aryl groups, and a chair,chair conformation (1-4 and 6-9), in addition to the α-amino acid (3S)-hydroxy-3',4'-dimethoxy-L-phenylalanine (5), veratric acid (10), and β-sitosterol (11), were isolated from the powdered and defatted air-dried aerial parts of Leucophyllum ambiguum. Four of these lignans, ciquitins A-D, 1-4, were isolated for the first time as natural products. The structures of these compounds were established based on their spectrometric/spectroscopic data. Additionally, single-crystal X-ray crystallography confirmed the structure of ciquitin A (1), and derivatization with (9S)-naproxen and X-ray diffraction crystallography data established its absolute configuration. Ciquitins A (1) and B (2) possess a 9-hydroxy group; this chemical characteristic grants these species conformational isomerism not seen in the other six lignans. The conformers of 1 and 2 are distinguishable via their ¹H and ¹³C NMR spectroscopic data. This is the first report of this phenomenon, and hence, a complete assignment of the signals in both spectra of each conformer for each compound is presented. Compounds 1-9 were found to exhibit potent inhibitory activity in the 1.0 × 10^-3 to 2.2 μM range against acetylcholinesterase, an enzyme directly involved in the etiology of Alzheimer's disease and senile dementia. Thus, these natural products are promising agents that are potentially useful for the treatment of neurological degeneration.