Isolation Of The Chemical Constituents Of Erigeron Acer And Synthesis, Biological Evaluation And SAR Studies Of Unsymmetrical Biphenyls

In the first part of this thesis the chemical components of Erigeron acer collected in Zhangxian County, Gansu Province, were investigated. About 200 species belong to the Erigeron family (Compositae) in the world, of which 35 are distributed in China, mainly in Xinjiang and the mountains of Southwest China; only 4 species have been used as Chinese folk medicines. Much research has been done on Erigeron breviscapus by Chinese researchers due to its good bioactivities. Erigeron acer belongs to the Erigeron family, which is distributed extensively in China. There has been no report about its usefulness in medicine and its chemical components.32 compounds with various structural types were isolated from Erigeron acer by means of silica gel column chromatography (CC), preparative thin layer chromatography (PTLC) and recrystalIization etc. The structures of 28 compounds were elucidated on the basis of spectroscopic methods (IR, MS, ¹H-NMR, ¹³C-NMR, DEPT, 2D-NMR and CD, etc). Among them, one sesquiterpene, one diterpene glycoside and two butenolide derivatives are new compounds.Schisandra chinensis is used as a tonic and astringent drug in traditional Chinese medicine. Its major constituents, dibenzocyclooctandiene lignans, exhibit antitumor, antihepatotoxic (liverinjury), anticonvulsive, anti-HIV and antifungal activities. In the 1970s, it was found in clinical studies that Schisandra chinensis could decrease SGPT, and this result attracted the attention of many scientists. 4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'-dicarboxylate (α-DDB) and bicyclol, which were obtained from Schisandra chinensis, are being developed as new medicines for hepatopathy, and the biphenyl structural unit of these natural products is crucial for their pharmacological activities.The second part of this thesis described the synthesis of 65 unsymmetrical biphenyl derivatives, evaluated their activities and discussed their structure-activity relationship (SAR). (1) Activity evaluation: a) Antitumor activity: all the 65 compounds were assayed against A549, PC-3, DU145, KB, KBVIN cell lines to evaluate their antitumor activity. The values of GI50 were measured by SRB method with antitumor drugs homoharringtonine and etoposide as positive controls. The result showed that compounds 48 and 51 have good activity with GI50 value of 0.04μM against the above cell lines; especially, compounds 23, 27, 46, 48, 51, 54 showed good inhibitory activity against KBVIN which are resistant to other antitumor medicines, b) Anti-HIV activity: 20 compounds were assayed in MT-2 cell lines to evaluate their anti-HIV activity. Some compounds were evaluated in H9 cell lines. The results showed that 8 and 46 exhibited potent anti-HIV activity in MT-2 cell line with TI values of 14 and 16.6, respectively. (2) SAR analysis of antitumor activity: a) Aldehyde group is a necessary group and the activity of compounds with two aldehyde groups are better, b) A bigger acyl group is favorable for activity, c) The methlyenedioxy group in the molecular is useful for elevating the activity, but its position is irrespective of the activity, d) A six-member-ring lactone is more favorable than a seven-member-ring lactone in elevating the activity.The results of this thesis offer phytochemical proofs for plant chemotaxonomy and for exploiting and utilizing natural resources; they also provide some theoreticalevidence to the research and development of antitumor and anti-HIV medicines.