Study On The Antitumor Constituents From Tylophora Atrofolliculata Metc And Synthesis Of Phenanthroindolizidine Alkaloids

In order to look for new antitumor agents from plant resources, Tylophora atrofolliculata Metc., a species of Tylophora genus growing in Guangxi Province, People's Republic of China, was subjected to phytochemical and antitumor studies. 22 compounds were isolated from the alcohol extract of the rhizomes of the title plant, including 5 new compounds, eight of them were alkaloids. Their structures and some of the stereochemistry were elucidated by means of various modern spectroscopic techniques and chemical methods.Among the new compounds, there were 4 alkaloids named Tylophoridicine D (1), Tylophoridicine E (2) ,tylophoridicine C (3) and tylophoridicine F (4). Another one compound was a new steroid named tylophoriside A (5).The known compounds isolated from Tylophora atrofolliculata Metc. were O-methyl -tylophorinidine (6), tylophorinidine (7), S-(+)-desoxytylophorinine (8), R-(+)-desoxy -tylophorinidine (9), quercetin (10), dihydroquercetin (11), myricetin (12), dihydromyricetin (13), oleanolic acid (14), echinocystic acid (15), tyloupenol B (16), (S)-13-hydroxy-9Z,11E -octadecadienoic acid (17), palmitic acid (18), p-hydroxy acetophenone (19), 3-hydroxy -4methoxy-acetophenone (20),β-sitosterol (21) and baucosteyl (22)。The anticancer test in vitro against human tumor cell lines indicated that all of the alkaloids from the roots of Tylophora atrofolliculata Metc. showed cytotoxic activity against KB and HCT-8 human tumor cells at different level and showed some selectivity on certain human tumor cell lines, and thus were responsible for the bioactivity of the plant.In addition, we have been working on methodology of rapid and effective separation and identification together with activity testing of minimum-quantity alkaloids in Tylophora atrofolliculata Metc. using HPLC-MS, HPLC-MS-MS, HPLC-UV and HTS. We have gotten some structural information of those minimum-quantity alkaloids.The very small quantity and the unique biological activity of phenanthroindolizidine alkaloid have encouraged us to develop a short and flexible total synthesis of these alkaloids. In the thesis, we focus effort on the total synthesis and semi-synthesis of natural product, phenanthroindolizidine alkaloid (Deoxytylophorinine) showing antitumor activity, which was isolated by our group, in order to provide enough samples for pharmacology research and study stucture activity relationships of those alkaloids. We use Diazo-couple and reductive aminate reaction to synthesize the core of the alkaloid directly. It has the potential to be extended into a total synthesis of those intersting natual products.We have finished the semi-synthesis successfully. At the same time an asymmetric total synthesis route of this natual product was designed, and a preliminary studies on chiral core of this natural product were carried out.