Synthesis,Characterization And Anticancer Activity Of Four Kinds Of Pentacyclic Triterpenoids

Pentacyclic triterpenoids are widely distributed in the plant kingdom.A large number of studies have shown that,as long as have the skeletone of triterpenoids are has potent antitumor,antibacterial,anti-inflammatory,anti-HIV and other pharmacological activities,and also showed strong hepatoprotective activity.But pentacyclic triterpenoids have low water solubility,and low bioavailability,its clinical application is limited.Based on the combination principle,we used natural product oleanolic acid,ursolic acid,18?-glycyrrhetinic acid and asiatic acid as starting materials,through a series of structural modification to increase polarity and the solubility in water,in order to get pentacyclic triterpenoid derivatives with higher efficiency and lower toxicity.This thesisis divided into three parts:The first part:Briefly introducing the research progress of four kinds of pentacyclic triterpenoids.Applications for pharmacdogical effects and clinical application,also prospecting their developments.The second part:Design,synthesis and characterization of oleanolic acid,ursolic acid,18?-glycyrrhetinic acid and asiatic acid derivatives.Thirty four new derivatives were synthesized,1.Esterification the C-28 carboxyl of oleanolic acid and ursolic acid,benzyl protection of C-3 oxhydryl,reducing C-28 ester group to alcohol,introducing the butanedioic acid,removing the protecting groups,then coupling with N-Boc-piperazine,methyl piperazine and morpholine,after removing the protecting group,eighteen oleanolic acid and ursolic acid derivatives are synthesized(OA-1-OA-7,8(a-b),UA-1-UA-7,8(a-b));2.Firstly,protection with acetyl which C-3 oxhydryl of oleanolic acid,ursolic acid,18P-glycyrrhetinic and asiatic acid,Then C-28 carboxyl chlorination,condensation with glycolic acid,coupling with benzyl piperazine,methyl piperazine,after removing the protecting group,twenty pentacyclic triterpenoid derivatives are synthesized(OA-9-OA-13,UA-9-UA-13,GA-9-GA-13,AA-9-AA-13);3.Esterification the C-28 carboxyl of oleanolic acid,ursolic acid,18?-glycyrrhetinic acid and asiatic acid,introducing connecting fragment succinic acid at C-3 position,then coupling it with methyl piperazine,eight pentacyclic triterpenoid derivatives are synthesized(OA-14,OA-15,UA-14,UA-15,GA-14,GA-15,AA-14,AA-15);Thirty four new compounds were characterized by IR,1H NMR,13C NMR etc spectrogram.The third part:The study of anticancer activity of all compounds.The results indicated that OA-4,OA-7,UA-4,UA-7,OA-8a,OA-8b,UA-8a,UA-8b,OA-13,UA-13,GA-13,AA-13,OA-15,UA-15,GA-15,AA-15 had anticancer activities to MCF-7,and OA-4,OA-7,UA-4,UA-7,OA-8a,OA-8b,UA-8a,UA-8b had anticancer activities to Hela and A549,and equally as well the IC50 of positive control Gefitinib.