Synthesis Of Active Steroidal Glycosides And Flavonoid Glycosides

Steroidal glycosides and flavonoid glycosides widely occur as natural products. They act as active components of many medical plants and exhibit various bioactivities. In this thesis a series of steroidal glycosides and flavonoid glycosides were synthesized, and their structures were determined. This serves as a basis for testing their bioactivities, revealing the relationships between structure and bioactivity and developing new medicines.i) An Improved Synthesis of Polyphyllin DPolyphyllin D, a steroidal triglycoside with a 2, 4 - branched sugar residue, shows excellent cytotoxicities. Using D-glucose and diosgenin as starting materials, the key diol glycosyl acceptor 15 was prepared via protective group modulations and a glycosilation reaction. The glycosylation product 31 at the 2 - OH position was regioselectively obtained in 71% yield by the reaction of acceptor 15 with L-rhamnopyranosyl trichloroacetimidate 21 protected by Piv. The coupling reaction of 31 with L-arabinofuranosyl trichloroacetimidate 40 produced triglycoside 41, which was followed by deprotection with LiOH to afford Polyphyllin D in 36% overall yield via 9 steps. Following the procedure, 3.5g of Polyphyllin D was prepared to test its bioactivities.ii) Syntheses, Structural Characterization and Bioactivities of Monomethylated Dioscin Derivatives 42 ~ 49To explore the relationships between structure and activity of saponin Dioscin, all possible eight new monomethylated Dioscin derivatives were prepared. Based on the regioselective etherification and esterification reactions mediated by Bu2SnO, rhamnopyranosyl donor 70 and 74 with the methyl groups at positions 2 and 3, respectively, were prepared from allyl rhamnoside. Likewise, diol glycosyl acceptors 85 and 89 with the methyl groups at positions 3'and 6', respectively, were obtained from trillin. After the glycosylation of 85 and 89 with trichloroacetimidate 18 and the deprotections, the monomethylated Dioscin derivatives 42 and 43 were produced, respectively. The target molecules 44 ~ 46 were produced by couplingmonoglycoside 87 with thioglycoside 53 and trichloroacetimidate 70 and 74, modifying protecting groups, glycosylation with compound 18 and deprotections. After diglycoside 107 reacted with 53, 70 and 74, the saponins 47 ~ 49 were synthesized by deprotection. The total assignment of 1H and 13C spectral lines of monomethylated dioscin derivatives 42 ~ 49 by means of ID and 2D NMR techniques and the effects of methylation on 13C chemical shifts of various sugar rings were discussed. Their inhibitory activities against P388 and A-549 cell were determined, and the results demonstrated that six of the eight hydroxyl of dioscin are the "key polar groupings" for tumor inhibitory activities and 6-OH and 4-OH might act as the positions of Dioscin for further modification.iii) Synthesis of Quercetin 3-O-(2"-Galloyl) L-Arabinopranoside (111):Quercetin 3-O-(2"-Galloyl)-L-Arabinopranoside 111, a typical representative of plant flavonol glycoside family, shows HIV-1 integrase inhibition (IC50 = 18.1g/ml). The three-benzyl protected derivative 141 were prepared from quercetin. The glycosylation reaction under phase transfer catalysis (PTC)conditions and selective removal of the acyl groups on phenolic hydroxyl were the key steps of the reaction procedure. The target molecule 111 was obtained in a yield of 5.6% via 12 steps. After further improvement, the compound 111 was more effectively produced in 13% yield via 10 steps using easily available 147 with two Bn protecting groups as glycosyl acceptors.iv) An Facile Syntheses of Flavonoid 7-0-GlycosidesFlavonoid 7-OGlycosides are an important class of natural products. An facile method was developed to synthesize this type of glycoside. The PhSH / imidazole / NMP catalysis system was utilized to regioselectively carry out the ester exchange reactions at position 7 on flavonoids to produce liberated 7-OH flavonoids. The resulting flavonoid algycones were smoothly coupled with (N-phenyl) trifloroacetimidate in the presenc...