Lysimachia Chemical Composition And Biological Activity And Chemical Conversion Of Synthesis

Lysimachia clethroides Duby belongs to the genus Lysimachia of the family Primulaceae, distributed widely in many provinces of China. The aerial parts of this plant have been used for treatment of throat ache, edema, and menoschesis, etc. Previous phytochemical studies on L. clethroides have led to the isolation and identification of triterpenoid saponins, flavonoids, and several other components.The aerial parts of L. clethroides were investigated on their chemical constituents systematically by various kinds of chromatographic methods. The sructures of isolates were elucidated on the basis of spectroscopic analysis and chemical methods as well. Some of them in sufficient amount were assayed for their bioactivities. The aerial parts of L. clethroides were collected from Mount. Lushan of Jiangxi province and identified by Professor Ce-Ming Tan (Jiujiang Institute of Forestry).Seventy-three compounds were obtained from70%EtOH extract of the aerial parts of L. clethroides, including thirty-seven compounds from EtOAc extract and thirty-six ones from n-BuOH-soluble extract. These compounds were identified as follows:clethroidosides A-H (1*-8*), lysilactones A-D (9*-12*), E-3-carboxy-2-pentene-1,5-dioate5-ethyl ester (13*), E-3-carboxy-2-pentenedioate6-ethyl ester (14*), E-3-carboxy-2-pentenedioate1-ethyl ester (15*), protocatechuic acid-3-O-β-D-xylopyranoside (16*), vanillic acid-4-O-β-D-(2-O-is-p-coumaroyl)glucopyranoside (17*),(methoxycarbonylmethy1)phenyl-4-O-β-D-glucopyranoside (18*), quercetin-3-O-β-D-(6-O-Z-p-coumaroyl)glucopyranosi-de (19*),1-O-(9Z,12Z-octadecadienoyl)-3-O-[β-D-galactopyranosyl-(1→6)-O-β-D-galactopyranosyl-(1→6)-α-D-galactopyranosyl] glycerol (20*), monomethyl3,3',4,4'-tetrahydroxy-β-truxinate (21*),3-carboxyethyl-3-hydroxylglutaric acid1,5-dim-ethyl ester (22*),3-O-β-D-glucopyranosyl-(1→2)-[a-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranosyl-3β,16a,28-trihydroxyolean-12-ene (23), candidoside (24), ardisianoside E (25),3-O-β-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)]-α-L-arabinopyranosyl-13β,28-epoxy-3β,16α-dihydroxyoleanane (26), lysikokianoside1(27), ardisimamiloside E (28), itaconic acid (29), protocatechuic acid (30),E-p-coumaric acid (31), caffeic acid (32),3,4-dihydroxyphenylacetic acid (33), protocatechuic acid-4-O-β-D-glucopyranoside (34), a-resorcyclic acid-3-O-β-D-glucopyranoside (35), gentisic acid-5-O-β-D-glucopyranoside (36), vanillic acid-4-O-neohesperidoside (37), nipagin acid-4-O-neohesperidoside (38),p-hydroxyphenylacetic acid-4-O-β-D-glucopyranoside (39),kaempferol (40), quercetin (41), corbulain Ib (42), astragalin (43), isoquercitrin (44), isorhamnetin-3-O-β-D-glucopyranoside (45), quercetin-3-O-β-D-6"-acetylglucopyranoside (46), quercetin-3-O-β-D-(6-O-E-p-co-umaroyl)glucopyranoside (47), kaempferol-3-O-β-D-(6-O-E-p-coumaroyl)glucopyr-anoside (48), kaempferol-3-O-β-D-(6-O-Z-p-coumaroyl)glucopyranoside (49), quercetin-7-O-β-D-glucopyranoside (50), prunin (51),2-hydroxynaringin-5-O-β-D-glucopyranoside (52-53), kaempferol-3-O-rutinonoside (54), kaempferol-3-O-robinobioside (55), rutin (56), kaempferol-3,7-di-O-β-D-glucopyranoside (57), apigenin-6-C-β-D-xylopyranosyl-8-C-α-L-arabinopyranoside (58), apigenin-6,8-di-C-α-L-arabinopyranoside (59), apigenin-6-C-α-L-arabinopyranosyl-8-C-β-D-xylop-yranoside (60), apigenin-6,8-di-C-β-D-xylopyranoside (61), apigenin-6-C-β-L-ara-binopyranosyl-8-C-β-D-glucopyranoside (62), apigenin-6-C-α-L-arabinopyranosyl-8-C-β-D-glucopyranoside (63), apigenin-6-C-β-D-glucopyranosyl-8-C-α-L-arabino-pyranoside (64), blumenol A (65),(3S,5R,6R,7E,9S)-megastigman-7-ene-3,5,6,9-tetrol3-O-β-D-glucopyranoside (66), actinidioionoside (67),1-O-(9Z,12Z,15Z-octadecatrienoyl)-3-O-[β-D-galactopyranosyl-(1→6)-O-β-D-galactopyranosyl-(1→6)-α-D-galactopyranosyl] glycerol (68), malic acid1-methyl-4-ethyl ester (69), benzyl-O-β-D-glucopyranoside (70), leudrin (71),2-ethyl-3-methylmaleimide N-β-D-glucopyranoside (72), daucosterol (73).Among the isolated seventy-three compounds, there were fourteen triterpenoid saponins (1*-8*,23-28), four dibenzo-α-pyrones (9*-12*), seventeen organic acids (13*-18*,29-39), twenty-six flavonoids (19*,40-64), three nor sesquiterpenes (65-67), two glyceroglycolipids (20*,68), one lignan (21*) and six other components (22*,69-73). Twenty-two compounds (1*-22*) were new compounds.The cytotoxic activities of sixty-nine compounds obtained from the aerial parts of L. clelhroides were evaluated against five human tumor cell lines by MTT method. Compounds3-4,6and25-27exhibited moderate cytotoxic activity with IC50values of0.75-2.62μM, while compound5showed selective cytotoxic activity.By the model of inhibiting the production of lipid peroxide induced by Fe2+-Cys system in the liver microsomal, twelve new compounds were evaluated for their antioxidant activities. Compounds9,18,19,21showed moderate activity, which was comparative to the positive control Vitamin E.By the model of acetaminophen-induced hepatic injury, we tested hepatoprotec- tive activities of forty-eight compounds. Compounds52-53,54exhibited moderate activity, which was comparative to the positive control Bicyclol.The aldose reductase inhibitory activity was performed for thirty-six compounds isolated from the aerial parts of L. clethroides. The resulst showed that eight compounds (including three new compounds12,17,19, and five known ones44,47,49,51,54) possessed significant inhibition agaist aldose reductase, with IC50values of1.0-5.12μM.Meanwhile, we have finished the chemical conversion from a triterpenoid saponin of olean-12-ene type to olean-12-one type and total synthesis of a dibenzo-a-pyrone derivative (lysilactone A).