Studies On The Chemical Constituents Of Dysosma Versipellis And Structural Modification Of Its Major Component Podophyllotoxin

Dysosma versipellis (Hance) M. Cheng belongs to genus Dysosma, Berberidaceae Family. This medical plant was first recorded in "Shen-Nong-Ben-Cao-Jing". It is the main plant source of "Gui-Jiu". This herb was reported to possess antitumor, antiviral, antibacterial and antivenom properties.In order to obtained more podophyllotoxin analogs, a systematic investigation of the chemical components of Dysosma versipellis was carried out. Fifteen compounds were isolated from EtOAc and n-Butanol fraction of the 95% ethanol extract of the roots of Dysosma versipellis by Silica gel column, Sephadex LH20, and reverse phase HPLC chromatography, and the structures were elucidated by spectral analysis and physicochemical properties. The compounds included ten lignans, i.e.4',5'-didemethylpodophyllotoxin (1), podophyllotoxin (2),4'-demethylpodophyllotoxin (3), diphyllin (4), podophyllotoxone (5), picropodophyllotoxin-4-O-β-D-glucoside (6),4'-demethylpod-ophyllotoxin-4-O-β-D-glucoside (7), diphyllin-4-O-β-D-glucoside (8), podophyllotoxin-4-O-β-D-glucoside (9) and dysosmarol (10); four flavonoids, i.e. kaempferol (11), quercetin (12), kaemp-ferol-3-O-β-D-glucoside (13), quercetin 3-O-β-D-glucoside (14) and one sterol, i.e.β-sitosterol (15). Compound 1 is a new natural product, and compounds 7 and 8 are isolated from genus Dysosma for the first time.The isolated compounds were tested for their inhibitory activities against the prostate cancer cells. We found that the podophyllotoxin showed good inhibitory activity against the prostate cancer cells. The aglycones showed stronger activity than glycoside and the flavonoids only exhibited weak inhibitory activity.Podophyllotoxin has remarkable antitumor activity, but it is not suitable for clinical application because of its strong side effects. In order to obtain the more effective and less toxic antitumor drug, structural modification of podophyllotoxin was performed. Eight compounds were synthesized and their structres were characterized by physicochemical properties and spectral analysis, i.e. (1R,2R,3R,4R)-4-ethylthio-4-deoxypodophyllotoxin (16), (1R,2S,3R,4R)-4-ethylthio-4-deoxypodophyllotoxin (17), (1R,2R,3R,4R)-4-sulfhydryl-4-deoxypodophy (18),4-methoxy-4'-demethylpodophyllotoxin (19),4-methoxypodophyllotoxin (20),3,4-didehydro-4-deoxy-podophyllotoxin (21), methyl 7-hydroxymethyl-8-methoxy-5-(3,4,5-trimethoxy- phenyl)-5,6,7,8-tetrahydronaphtho [2,3-d] [1,3] dioxole-6-carboxylate (22) and methyl 7-(meth-oxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho [2,3-d] [1,3] dioxole-6-carboxylate (23).In addition, the reaction mechanism was discussed. The anticancer assay of these compounds is still in progess.