Studies On The Chemical Constituents And Bioactivities Of Alstonia Scholaris,myrrha And Olibanum

This dissertation investigated the chemical constituents and bioactivities of three traditional medicinal plants and resins,Alstonia scholaris,Myrrha and Olibanum.Based on various chromatographic,extensive spectroscopic methods(1D and 2D NMR,MS,UV,IR,ORD,CD),X-ray diffraction,and quantum chemical calculations of ECD spectra/NMR chemical shifts,total 115 compounds including 52 new ones(11 new skeletons)were obtained from these three traditional medicines.The structural type of the isolates involved alkaloids,terpenoids,dimer-terpenoids,and steroids.Moreover,the pharmacological investigations showed that some isolates exhibited prominent biological bio activities,which not only would account for scientific knowledge for their traditional use,but also provide credible theoretical foundation for further development.This dissertation contains two chapters consisting of four sections,in which the investigations on the chemical constituents and bioactivities of Alstonia scholar is,Myrrha and Olibanum are presented in detail.1.Studies on the chemical constituents and bioactivities of Alstonia scholaris.A.scholaris(Apocynaceae)is an evergreen tree,widely distributed in tropical Africa and Asia,which is historically used in "Dai" ethnopharmacology in China with its roots,stems,bark and leaves.Following its folk description,the non-alkaloids fraction from A.scholaris were investigated,and the results indicated the fraction exhibited antihyperuricemic bioactivity.Subsequent phytochemical investigation on the non-alkaloids fraction of A.scholaris led to the isolation of 32 compounds,including 9 new ones(2 new skletons with unique 6/6/6/7/5 and 6/6/5/6/6/6 ring systems,7 new triterpenoids),22 known analogues and 1 known steroid.Compounds 1-25 were evaluated for their antihyperuricemic bioactivity in vitro and in vivo,and as a result,compounds 1,2,3,10,17,20,and 23 could reduce the serum UA level significantly.Monoterpenoid indole alkaloids(MIAs)are attractive for organic synthetic chemists and biologists for their complex and changeable structures,and diverse bioactivities.Based on our previous study,many part of the A.scholaris are rich in MIAs.There are some differences in HPLC chromatograms between the 6 years stored leaves and fresh leaves,and the anti-tussive efficacy reduced significantly.Inspired by the change of chemical composition,the phytochemical investigation on the 6 years stored total alkaloid of the leaves of A.scholaris was carried out.As a result,21 MIAs were isolated,including 14 new ones(2 new skeletons possessing unique 6/5/5/6/6/5/3 aziridine containing ring systems,12 new MIAs)and 7 known analogues.According to the studies on biosynthetic pathway,most of the obtained new compounds were the derivatives of picrinine.All of the compounds were evaluated for their anti-inflammatory bioactivity via detecting inflammatory mediator releases(TNF-α、COX-2 and PGE2)in RAW 264.7 macrophage cells induced by LPS,and most of the isolates exhibited significantly anti-inflammatory bioactivity.2.Studies on the chemical constituents and bioactivities of Myrrha and Olibanum.Myrrha is the dried resin of Commiphora myrrha Engl.and Commiphora molmol Engl.,widely distributed in tropical and subtropical regions,the southern Arabia and India.Olibanum is the dried resin of Boswellia carterii Birdw.and Boswellia bhaurdajiana Birdw.,widely distributed in Southern Arabia,Africa and India.Myrrh and Olibanum are traditional medicines used to promote blood circulation,remove blood stasis and relieve pain.They are often used together to enhance the efficacy in Traditional Chinese Medicine.After long-term exploration,our group established characteristic isolation and purification methods for resin.Based on our previous study,the continued phytochemical investigation on myrrh led to the isolates of 30 compounds,including 12 new compounds(7 new skeletons).Different diterpene and sesquiterpene were polymerized by[4+2]Diels-Alder cycloaddition reaction,resulting in complex novel structures.Moreover,32 compounds were isolated and identified from Olibanum,including 17 new compounds,most of which were cembranoid-type diterpenes.Biological study showed that compounds 1-3 isolated from myrrh suppress tumor sternness in esophageal cancer by inactivating the Hippo/Yap pathway,and compounds 8-10 reduced cellular lipid accumulation in metabolism of fatty acids by regulating the AMPK/ACC pathway in hepatocytes.