Studies On The Chemical Constituents And Biological Activities Of Kadsura Coccinea And Isodon Pharicus

This dissertation is consist of three chapters. The chapters 1 and 2 described the chemical constituents and biological activities of Kadsura coccinea(Kadsura) and Isodon pharicus (Isodon), the chapter 3 was a review about the progress of chemical constituents and bioactivities of triterpenoids from Kadsura species between 2005 and 2015.143 compounds, including 81 new ones, were isolated from the above-mentioned two species by various separation methods. And their structures were determined based on extensive spectroscopic analysis in conjunction with quantum chemical calculations and single-crystal X-ray diffraction analysis. These compounds consisted of triterpenoids, diterpenoids, sesquiterpenoids, etc.All the isolates from K. coccinea belonging to the medically important plants of the Kadsura genus, were mainly composed of triterpenoids, which were classified into 14(13?12)-abeo-6/6/5/6-fused rearranged lanostane-type, 18(13?12)-6/6/6/5-fused rearranged lanostane-type, and 6/6/6/5-fused lanostane-type and so on. A triterpenoid bearing an unprecedented 6/6/9-fused skeleton, which was characterized by a unique oxabicyclo[4.3.1]decane moiety replacing the 5/6-fused C/D rings, was firstly discovered. Simultaneously, a pair of 18(13?12)-26-nor-6/6/6/5-fused rearranged lanostane-type triterpenoids differing in the configurations of C-23 and C-24 in the epoxy unit of the side chain, were also discovered for the first time. Besides, a novel skeletal 6/4/6-fused sesquiterpenoid was also firstly discovered, which might plausibly be traced back to the cadinane-type sesquiterpenoid.The ?. pharicus (Isodon) which has been discovered by our group at the highest elevation about 4200 meters, and the structural types of diterpenoids from this species were diverse and mainly attributed to 7,20-epoxy-ent-kaurane. Among them, a novel skeletal meroditerpenoid which was possibly formed by the nucleophilic addition of a 7,20-epoxy-ent-kaurane diterpenoid and a benzaldehyde was isolated. Meanwhile, novel diterpenoids possessing 15,16,17-nor-7,20-epoxy-ent-kaurane and 7,20-epoxy-ent-atisane frameworks were firstly discovered, and these results would enrich the contents of diterpenoids from Isodon genus.Chapter 1. Studies on the Chemical Constituents and Biological Activities of Kadsura coccineaKadsura coccinea (Lem.) A. C. Smith, a woody vine plant, belongs to the Kadsura genus (Schisandraceae), and are mainly distributed in the Jiangxi, Hunan, Guangdong, Hongkong, Hainan, Guangxi, Guizhou, Yunnan Provinces and so on. In the folk medicine, the roots and stems of this species were widely used to treat stomach illness, rheumatic arthritis, traumatic injury, and gynaecology related diseases. Our research group has once started phytochemical investigations on this species from the Honghe prefecture of the Yunnan Province and the Ziyuan prefecture of the Guangxi Province, showing that different sources might make a big difference in the chemical constituents, and the results further validated the general regulation of natural product chemistry that different ecological environments of the same species might be an important external factor for structurally diverse metabolites. Hence, a phytochemistry investigation on the stems of K. coccinea collected in the Menglun district of Xishuangbanna prefecture of the Yunnan Province resulted in the isolation of 56 compounds, of which 41 were new ones. The structure-activity relationships of these new ones were initially discussed for their cytotoxicity; besides, some new ones were tested for their antifungal activities.Chapter 2. Studies on the Chemical Constituents and Biological Activities of Isodon pharicusIsodon pharicus (Prain) Hara belonging to the Isodon genus (Lamiaceae) are perennial small shrubs and mainly distributed in the northwest of Sichuan Province and the southern district of the Tibetan autonomous region, China. In the folk medicine, this species has been commonly used for deinsectization and the treatment of inflammation of the eyes. Our research group has studied the I. pharicus collected in the Lhasa area, Tibet autonomous region, People's Republic of China, and several compounds with good antitumor activity were discovered. For instance, pharicin A could disturb the mitotic progression of several leukemia and solid tumor-derived cells, and induce of the mitotic arrest (G2/M) and apoptosis; Pharicin B could stabilize the RAR-a protein and enhence all-trans retinoic acid (ATRA) for the differentiation of several AML cell lines, especially some primary leukemic cells in the acute promyelocytic leukemia (APL) patients. Meanwhile, some unique environments, such as high altitude and strong ultraviolet might induce the plants to produce structurally diverse metabolites. To discover more structurally novel and bioactive constituents, we started a phytochemical investigation on the high-altitude Gongbujiangda district (about 4200 meters) of Tibet autonomous region, China. As a result,87 diterpenoids including 40 new ones were isolated from this species, whose structural types were extremely diverse and referred to sixteen types, which mainly consisted of 7,20-epoxy-ent-kaurane diterpenoids.In this study, most of the new compounds were initially tested for the cytotoxicity.Chapter 3. Review:Progress in chemical constituents and bioactivities of triterpenoids from the Kadsura speciesThe medically important plants of the family Schisandraceae consisted of two genera Schisandra and Kadsura, about 30 species of which were found in China, and only ten species of the Kadsura genus were distributed throughout southeast to southwest China. In the folk medicine, the roots and stems of the Kadsura species were widely applied for their widespread uses to treat activating blood and dissolving stasis, promoting qi circulation to relieve pain. Modern studies on the chemical constituents and pharmacologic activities showed that triterpenoids were a kind of important active ingredients of this genus, exhibiting antitumor and anti-HIV activities. To have a more comprehensive understanding on the chemical constituents and bioactivities of triterpenoids from the Kadsura species and make the further studies more convenient, we summarized the chemical constituents and bioactivities of triterpenoids (classified into lanostane-type, cycloartane-type, and schinortriterpenoids) from the Kadsura species from 2005 to 2015, and provided valuable reference material.