| The thesis is consisted of two parts, including one study on the chemical constituents and bioactivity from seed of Strychnos nux-vomica L., and the other study on the chemical constituents from the endophyte fungi Aspergillus fumigatus Fresen. of Erythrophleum fordii Oliver.Strychnos nux-vomica L. belongs to the genus of Strychnos L. in the family of Loganiaceae, and is widely distributed throughout tropical and subtropical regions of the world with approximately 200 species, of which only nine are found in China.Strychnos nux-vomica L. have been used in traditional Chinese medicine for hundreds years, and it is used for the treatment of rheumatoid arthritis, swelling pain, trauma,bone fracture, facial nerve paralysis, myasthenia gravis and poliomyelitis sequela in clinic. A large numbers of studies on the chemical constituents of Strychnos nux-vomica have been carried on all over the world from the early 19th centuries.Previous studies on the chemical constituents of Strychnos nux-vomica led to the isolation of many compounds, including alkaloid, terpenoids and organic acids derivatives. So far, a large number of alkaloids have been isolated from Strychnos nux-vomica. In order to excavate bioactive new compounds, the trace alkaloids of Strychnos nux-vomica L. have been studied, and 42 compounds including 25 alkaloids,7 lignans, 4 monoterpenes and 6 phenolic acide derivatives were isolated and identified. Through spectroscopic methods and chemical methods, their structures were established as stryvomicine (1), stryvomitine (2), isopseudostrychnine (3),5-oxobrucine (4) , 5-oxopseudostrychnine (5), 11 -hydroxyl-icajine (6),10-hydroxyl-icajine (7) , 5-hydroxyl-vomicine (8) , deoxy-isostrychnine-chloromethochloride (9),strychnine (10),pseudostrychnine (11),brucine (12),pseudobrucine (13),icajine (14),vomicine (15),novacine (16),icajine-N-oxide (17),pseudo-a-colubrine (18), 12-hydroxyl-pseudostrychnine (19), 12-hydroxyl-strychnine(20), 15-hydroxyl-novacine (21) , deoxy-isostrychnine (22), strychnine-chloromethochloride (23),indole-3-carboxaldehyde (24), indole-3-ethanol (25),decedrusine A (26), dihydrodihydrodiconiferyl alcohol (27), isolariciresinol (28),secoisolariciresinol (29),erythro-guaiacylglycerol-?-O-4'-coniferyl alcohol (30),erythro-guaiacylglycerol-?-O-4'-dihydroconiferyl alcohol (31), 4,4'-dimethoxy-3-hydroxy-7,9',7',9-diepoxyligan-3-O-?-D-glucopyranoside (32), 1-deoxyloganin aglycone (33), dehydrovomifoliol (34), boscialin (35), 1-(-3-hydroxybut-l-enyl)-2,2,6-trimethylcyclohexane-1,4-diol (36), p-hydroxybentyletnene-ether (37),4-(2,3-dihydroxypropyl)-2,6-dimethoxyphenol (38),4-methoxyl-1,2-phenyldiol (39),hydroquinone (40), ferulic acid (41), 4-(2-hydroxyethyl)-2 -methoxybenzoic acid (42).Among them, compound 1 is a new skeleton, compounds 2-9 and 26 are new. The absolute configurations of 1 and was determined by comparison of their experimental and calculated ECD spectrum. The absolute configurations of 2, 6, 7, 8 and 26 were all determined by comparison of CD spectrum. The postulated biosynthetic pathway of 1 was also discussed. Some compounds were evaluated for cytotoxic, neurotoxic,anti-inflammatory and neuroprotective activities using in vitro cellular assays.Compounds 6 and 7 showed neuroprotective activities on PC 12 cells with IE 50 values of 0.68-4.81 ?M and 0.54-6.50 ?M, respectively.The genus Erythrophleum consists of 15 species in the world, widely distributed in tropical Africa, tropical and subtropical of Asian and northern of Australia, of which only one (Erythrophleum fordii Oliver) was found in China. In our preliminary studies,we found a series of cassaine-type diterpenoid alkaloids with diverse structures and interesting antitumor activity from the stem barks of E. fordii. Meanwhile, an array of endophytes was isolated from the stem barks of E. fordii, which identified to be Aspergillus fumigatus Fresen. by means of microscopic morphological observations and molecular series analysis. According to the cytotoxic activity and chemical screening results, the bioactive strain Lyb038 was selected for scale-up fermentation,and the EtOAc extract of its broth was then chemically investigated, leading to the isolation of ten compounds including nine cyclic dipeptides and one phenol derivatives. Through spectroscopic methods, their structures were respectively established as: fumitremorgin C (43), 8,9-dihydroxyl-fumitremorgin C (44),cyclo-(L-Pro-L-Trp) (45), N-prenyl-cyclo-(L-Pro-L-Trp) (46), cyclo-(L-Pro-L-Phe)(47), cyclo-(D-Pro-L-Leu) (48), 6-methoxyl-spirotryprostatin B (49), spirotryprostatin A (50), pseustin A (51), p-hydroxypenylethanol (52). The compounds were all assayed for cytotoxic activity. By means of microscopic morphological observations and molecular series analysis, Lyb038 was identified to be Aspergillus fumigatus Fresen. |
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