Design, Synthesis And Relevant Activity Evaluation Of Several Oleanolic Acid Saponins And Spinosad Derivatives

Oleanolic acid saponin is a typical type of triterpenoid saponin. It widely existsin a variety of medicinal plants.Which has antithrombotic，anti-inflammatory，anticancer， antivirus and immunoregulatory activities. Spinosad is a high qualitygreen biological pesticide，mainly obtained by biological synthesis method.We havesuccessfully synthetized of eight kinds of oleanolic acid saponins and three kinds ofnew type of spinosad derivatives through chemical method. The main research resultsare as follows：1. Used four kinds of monosaccharides (glucose，galactose，mannose andrhamnose) as sugar donors，and oleanolic acid (with28-carboxyl closed and notclosed) as receptor to synthesize throught trichloroacetimidate reaction method. Wepreliminarily explored oleanolic acid saponin’s chemical synthesis route. And wesuccessfully synthetized eight kinds of oleanolic acid saponins the structures wereidentified by1H-NMR and13C-NMR. The eight kinds of Oleanolic acid saponinrespectively named：3-O（-β-D-Glucopyranose) Oleanolic acid，3-O-(β-L-Rhamnose)Oleanolic acid，3-O-(β-D-Galactose) Oleanolic acid，3-O-(β-D-Mannose) Oleanolicacid，3-O-（β-D-Glucopyranose)-28-O-(β-D-Glucopyranose) Oleanolic acid，3-O-(β-L-Rhamnose)-28-O-(β-L-Rhamnose) Oleanolic acid，3-O-(β-D-Galactose)-28-O-(β-D-Galactose) Oleanolic acid，3-O-(β-D-Mannose)-28-O-(β-D-Mannose) Olean-olic acid.2. Study the process of hydrolysising spinosad by hydrochloric acid throughorthogonal method. The optimal hydrolysis conditions were：the concentration ofhydrochloric acid is0.5mol/L，the hydrolysis time is5hours，the best hydrolysistemperature is85℃. Hydrolyzed spinosad with0.5mol/L hydrochloric acid to removeits methoxy L-rhamnose，obtained C-9false aglycone.3. Used C-9false aglycone as receptor and three kinds of monosaccharide (gluc-ose，galactose and rhamnose) as donors synthesized throught trichloroacetimidatereaction method to obtain three kinds of new type of spinosad derivatives. Wesuccessfully created a chemical synthesis way to get spinosad derivatives.4. Explored the interaction of eight saponins with PAI-1by UV and fluorescencemethod，and comparing them with positive contrast Ginsenoside-Rg1. According tothe binding constant K to reflect the combination level of small molecule compoundswith macromolecular protein， used this as a model for screening strongerantithrombotic activity of the saponins. Results show that the binding constant K= 2.59×105L﹒mol-1between3-O-(β-L-Rhamnose)-28-O-(β-L-Rhamnose) Oleanolicacid and PAI-1is greater than the combination of positive contrast Ginsenoside-Rg1which has the constant K=6.77×104L﹒mol-1，suggests that it may have a betterantithrombotic activity. And the final result remains to be further research.