Studies On The Chemical Constituents Of Hypericum Scabrum L.

Hypericum scabrum L. is a specie of the genus Hypericum of the Guttiferae family, which were collected from Xinjiang Uygur Autonomous region. In the study of plants of the genus Hypericum, the reachers are very curious about it in the unique chemical composition and a various of pharmacological activity. At present, hundreds of monomer compounds have been isolated from plants of the genus Hypericum by the plant chemist. According to the biogenesis synthesis ways, these monomer compounds include phloroglucinols coming from a glutaric hydroxyl acid pathway, naphthodianthrones coming from acetic acid and malonic acid pathways, both flavonoids and xanthones coming from Shikimic acid pathway, and so on. Reports for the pharmacological activities of these compounds showed that plants of the genus Hypericum has antidepressant, antibacterial, antivirus, antitumor, and the function of cardiovascular protection.Phloroglucinols is one of the characteristic components of plants of the genus Hypericum. Due to its desirable pharmacological activity and fascinating chemical structure, the study of this kind of compound has become a hotspot in the field of medicine in recent years. Especially since2005, the total synthesis of garsubellin A that is a phloroglucinols compounds was firstly completed, which stimulated Organic chemist to put great effort on the synthesis of this kind of compounds and its derivatives. That is a very important role for further clarifying the relationship between complex structure and the various activity of phloroglucinols.As part of a program to assess the chemical and biological diversity of several traditional Chinese medicines, this dissertation investigated chemical constituents of the aerial parts of Hypericum scabrum L., and bioactivities of petroleum ether extracts and purified compounds on several pharmacological models with the help of pharmacological staff. In addition,(R)-3,4-dihydroxy benzoic acid-1’-glycerin ester have been isolated from Hypericum perforatum L. by the other members of our group, and it has the very good antidepressant activity in vitro. So this paper also involves the study of the synthesis of this compound, its derivatives and analogues.This paper aimed at studing the characteristic composition phloroglucinols that was contained in Hypericum scabrum L.. By using various chromatographic techniques and spectroscopic methods,34puried compounds from petroleum ether fraction of Hypericum scabrum L. have been isolated and identified, which included thirty-one polyprenylated acylphloroglucinols, one triterpenes and two other kinds of compounds. Among them, twenty compounds were new, which contained one decarbon phloroglucinol component(19*), three transannulation phloroglucinol components(9*、10*、11*), two pyran-phloroglucinols(17*、18*), fourteen furan-phloroglucinols(1*-8*、12*-16*、20*). At the same time, through analyzing the struction of (R)-3,4-dihydroxy benzoic acid-1’-glycerol ester, we designed its synthetic route. It make us get a total of13compounds including the racemic target compound, its derivatives and analogues.In the in vitro assays, compound9*showed obvious [3H]-5-HT reuptake inhibitory activity. In the rat brain synaptosomes [3H]-NE uptake activity screening experiments, all kinds of crude extracts of H. scabrum exhibited significant NE reuptake inhibitory activity. The inhibition rates of14compounds (4*,5*,6*,7*,8*,9*,10*,12*,15*,16*,18*,19*,26,27) were all lower than50%. In the10μM concentration compounds21,25,28exhibited protective activity against a damage of hepatocyte, the survival rates were69%,71%,80%, with significance compared to the blank control group. The water and the petroleum ether extraction showed potent cytotoxicity. However, purified compounds did not show significant cytotoxicity activity and PTPIB inhibition activity.