Abstract: Leojaponin is a typical diterpene isolated and identified from the leaves of the traditional Chinese medicine Yimucao (Leonurus japonicus). It has a unique chemical structure bearing a furan moiety and a cross alpha, beta- unsaturated carbonyl, which is a pharmacophore for many drugs, and it can be chemically transformed into a series of derivatives. Also, some so called natural products isolated from L. japonicus might be artifacts transformed from leojaponin during the process of purification. Although leojaponin is not active against acetylcholinesterase, a similar compound isolated from the herb displayed moderate inhibitory activity on acetylcholinesterase. Therefore, establishment of the process of preparing leojaponin and derivation of this compound are of great importance in utilization of this medicinal plant. In this paper, the purification and chemical transformation of leojaponin are reported. The raw material was extracted with 95% ethyl alcohol, and then the solvent was evaporated to dryness by using a rotary evaporator. After that, the residue was dissolved in water and extracted with ethyl acetate, and fractionated by column chromatography on AB-8 macroporous resin. The collected fraction was separated and purified by semi-preparative HPLC. As a result, the purity of the product quantitated by HPLC normality was over 98%. And then three new derivatives have been synthesized by transformation of leojaponin through oxidation and Mannich reactions. All the chemical structures of the new compounds have been elucidated by using 1D and 2D NMR spectroscopic analysis. The in silica interactions between the four compounds and acetylcholinesterase have been performed, and the results showed that compound 2 had the best binding activity (-9.6 kcal/mol).Abstract: Leojaponin is a typical diterpene isolated and identified from the leaves of the traditional Chinese medicine Yimucao (Leonurus japonicus). It has a unique chemical structure bearing a furan moiety and a cross alpha, beta- unsaturated carbonyl, which is a pharmacophore for many drugs, and it can be chemically transformed into a series of derivative...Show More
