Studies On Oleanolic Acid Glycosylation And Structure-activity Relationship Resisting Magnaporthe Oryzae

Rice blast is one of the three most devastating diseases on rice worldwide every year.It not only decreases rice yield by 10%³0%, but also debases quality of rice. As the traditional chemical pesticides have many shortcomings, such as toxic, polluting the environment and it’s easy to produce drug-resistant strains, therefore, the development of new bio-pesticides on rice blast prevention is important. Oleanolic acid is a pentacyclic triterpenoids widely distributed in the nature which possesses various important bioactivities. Glycosylated modifications of oleanolic acid at C₃-OH, C17-COOH and C12=C13, can not only improve its low polarity, poor solubility in water, and low bioavailability, but also can greatly enhance or increase biological activity. The structure of sugar chain groups in synthetic saponin and certain specific groups are key parts of the activities. In this dissertation, structure and biological activities are reviewed of 205 synthetic oleanane type saponin, and discusses the structure-activity relationships between glycosylation type, quantity, connection, location, and special groups andα-glucosidase inhibitory activity, hemolytic activity, cancer inhibitory activity,antimicrobial activity. It provides molecular design ideas for developing new oleanane type drugs（including agrochemicals）.In this dissertation, oleanolic acid as a lead compound, glycosyl trichloroacetimidates and bromo-glycoside as donors, 26 oleanane type triterpenoid saponins have been designed and synthesized, including 14 oleanolic acid 3-glycosides, 7oleanolic acid 28-glycosides and 5 oleanolic acid 3,28-bisdesmonsides. Ten of them have never been seen in other articles, respectively, oleanolic acid3-O-α-L-rhamnopyranosyl-28-allyl alcohol ester（Rha-8）, oleanolic acid3-O-α-D-mannopyranosyl-28-allyl alcohol ester（Man-8）, α-D-mannopyranosyl oleanolate（Man-11）, oleanolic acid 3-O-β-D-galactopyranosyl-28-ene heptyl alcohol ester（Gal-8a）, oleanolic acid 3-O-α-L-arabinopyranosyl-28-ene heptyl alcohol ester（Ara-8a）, 3-O-β-D-glucopyranosyl-28-O-β-D-glucopyranosyl oleanolate（HYY-1）,3-O-β-D-xylopyranosyl-28-O-É‘-L-arabinopyranosyl oleanolate（HYY-2）,3-O-β-D-galactopyranosyl-28-O-É‘-L-arabinopyranosyl oleanolate（HYY-3）,3-O-É‘-L-arabinopyranosyl-28-O-β-D-galactopyranosyl oleanolate（HYY-4）,3-O-β-D-galactopyranosyl-28-O-β-D-galactopyranosyl oleanolate（HYY-5）.Inhibitory activity was determined of 26 synthetic saponins on magnaporthe oryzae by myceliμm growth rate method. Structure-activity relationship studies show:（ⅰ）Oleanane type saponins inhibitory activity against magnaporthe oryzae is mainly affected by the combined effects of glycosylation type, location, and the connection group of glycosylated C-28;（ⅱ）introducing hexose residues at C₃-OH of oleanolic acidis a favorable modification to enhance the antibacterial activity, especially, it’s mannose;（ⅲ）both introducing sugar residues and free carboxylic acid at C-28 of oleanolic acid are not conducive to improving the antimicrobial activity;（ⅳ）introducing small ester chains molecules（such as allyl） at C-28 of oleanolic acid helps improve antibacterial activity;（ⅴ）while introducing sugar residues at C-3 and C-28 of oleanolic acid disfavor antibacterial activity;（ⅵ）We believe that the introduction of mannose or other hexose residues at C₃-OH of oleanolic acid, and increase the nμmber of sugar molecules, while C-28 position connection small ester chains molecules, is the direction of molecular design to improve antibacterial activity.