Synthesis Of Oleanolic Acid Saponins

The dissertation describes the procedures for the synthesis of oleanolic acid saponins. A series of monosaccharide saponins are constructed through the glycosidic linkage with the aglycone, then the sugar chain are extend to synthesize a tetrasaccharide saponin and two trisaccharide saponins.Before the glycosylation of allyl oleanate, the commercially available sugars (D-glucose, D-galacotose, D-lactose, D-xylose and L-arabinose) are first transferred into the corresponding glycoyl trichloroacetimidates as donors (4a-4e). Secondly the 3-OH of allyl oleanate (5b) is coupled with a series of sugars through glycosylation method at the promotion of trimethylsilyl trifluoromethanesulfonate (TMSOTf) in good yields. Finally deprotection of the corresponding glycocongjugates afforded the target products (8a-8e).Oleanolic acid 3-yl (p-D-glucopyranoside) is regioselectively acylated in 3',6'-hydroxy groups with 1-(benzoyloxy)benzotriazole to afford 9. Compound 9 (acceptor) is glycosylated in the presence of TMSOTf with rhamose-derived trichloroacetimidates (donors) to provide target trisaccharide Saponin 1, oleanolic acid 3-yl-2,4-di-O-a-L-rhamnopyranosyl -p-D-glucopyranosideCoumpond 18 is prepared with oleanic acid and Bromide 11 through phase-thansfer catalysis glycosylation manner. The reaction of 18 and trichloroacetimidates 19 with TMSOTf afford trisaccharide Saponin 2, 3-0-{[D -glucopyranosyl-( 1 -3)]-a-L-arabinopyranosyl} -oleanolic acid-28-O-[|3-D-glucopyran -osyl]the Trityl oleanate 5b reacted with trichloroacetimidate 4e in the presence of a catalytic amount of TMSOTf at low temperature (-60癈), providing the desired glycoside 21, which is readily converted into the acid 22 upon warming to room temperature. Removal of the benzoyl-protection of 22 gives 23. Treatment of 23 with 2,2-dimethoxypropane and a catalytic amount of Pyridinium p-toluenesulfonate (PPTS) provids 24 with the 2-OH free. Glycosylation of 24 with trichloroacetimidate 4a leads to the trisaccharide saponin 25. Removal of the O-isopropylidine group affords diol 26. Diol 26 is acetylated regioselectively at4'-OH providing 28 Subsequently, 28 is easily arabinosylated with 4e to give the tetrasaccharide Saponin 3', 3-0-{[D-gIucopyrano-syl-(l->2)]-[a-L-arabinopy-ranosyl-(l3)]-a-L-arabinopyranosyl}-oleanolic acid-28-O-[-D-gluco-pyranosyl] ester.The structures of all the target products are characterized by IR, ' H NMR, 13C NMR, and tow-dimensional shift-correlated spectra (COSY, HMQC, HMBC).