Studies On The Structural Modification Of Ginsenoside With Antitumor Biological Activities

In this thesis, the structural modification of ginsenosides with antitumor biological activities were studied.A large number of study results indicated that three saponins, 20(S)- ginsenoside Rg3, 20(S)- ginsenoside Rh2 and 20(S)- protopanaxadiol from the fruits of panax quinquofolium L.,could inhibited tumor growth. But the less water solubility of them induce their clinical application limited. The research of chemical structure modification on them was meaningful to improve their dissolvability in water and enhancing their effect of anticancer.As synthesis raw material, 20(S)- ginsenoside Rg3, 20(S)- ginsenoside Rh2 and 20(S)- protopanaxadiol were obtained from the total saponin of panax quinquofolium L. fruit, and extracted by Macfofeticulaf Resin. Firstly the total saponins were hydrolyzed in alky glycerol at different temperatures. Then, the three saponins were isolated from hydrolysis products by gel silica column chromatography. Their chemical structures were identificated by 13C-NMR , 1H-NMR etc.Serials amino acids were choiced to combinate(reacted) with the saponins in the experiment, including glycine, alanine, phenylalanine, tryptophan, proline, arginine, lysine, aspartate, glumatic acid, histidine,methionine and cystine. The results showed that histidine didn't react with any saponins of them. Methionine and cystine can react with 20(S)-protopanaxadiol, but not with 20(S)-ginsenoside Rg3 and Rh2. Glycine and alanine were easy to react with experimental saponins. As the moleculer of the neutral amino acid are bigger, the combination reaction became more difficult. The basic amino acids have two amino group in moleculer, the extra amino group need be protected before the reaction. The Saponins amino derivates compacted with acidic amino acid such as aspartate and glumatic acid were difficult to be purified and separated.It was concluded that both Glc-6'and Glc-6"hydroxy of 20(S)- ginsenoside Rg3 were easy to react with amino acids, and the reaction was easier on Glc-6'. The C-20 hydroxy in 20(S)- protopanaxadio was difficult to react with amino acid , and the hydroxy at C-3 and C-12 can react with them in similar rate.43 saponin amino derivates were synthesized, they were all new compound. Some of them had the greater water solubility than 20(S)- ginsenoside Rg3, such as compounds 3,9. The oil/water partition coefficient of compounds 31, 32, 33 and 34 were less than 20(S)-protopanoxadiol, so their hydrophilicity were stronger than 20(S)- protopanoxadiol. The plasma protein binding ratio of compounds 3, 9 were more than 20(S)- ginsenoside Rg3 too. It could be presumed that their unticancer effects were increased.To improve water solubility of saponins, 5 oxidative products were synthesized by side chain bond oxidization with peracetic trifluoroacetic acid. Two of them were new compound. In addition, 20(S)- protopanoxadiol succinate was synthesized.All of the chemical structures of synthesized compounds were identificated by 1H-NMR and 13C-NMR. At the same time, a summary about the NMR characters of saponin amino derivates and saponin bond oxidative products was given on the basis of the spectral data.