Chemical Constituents From The Lianas Of Gnetum Pendulum And Gnetum Montanum F. Megalocarpum & Biomimetic Synthesis Of Active Oligostilbenes

Naturally occurring oligostilbene is a type of compounds with complex structures and muti-faceted bioactivities, polymerized by resveratrol or its derivatives (such as isorhapontigenin, oxyresveratrol, etc.) with different polymeric type or degree. In recent years, oligostilbenes have been found to have various biological activities, including anti-fungal, anti-inflammatory, anti-oxidant, anti-tumour, anti-cancer and anti-HIV, which have attracted more and more attention from worldwide researchers.The chemical studies on the progress in naturally occurring oligostilbenes have been reviewed in this thesis, as well as the oxidative-coupling in biomimetic synthesis. Mainly introduced in details, the chemical constituents from two Chinese Gnetaceae species, and the structure modification of oligostilbenes, the oxidative coupling reactions between different monomers, the prenylation of stilbene monomer and their polymerization. The pharmacological activities were tested on the obtained compounds, and the Structure-Activity relationships of stilbenes were discussed.From the lianas of two species of plants, Gnetum pendulum and G. montanum f. megalocarpum, 32 compounds were obtained altogether, among them, 8 were new including 4 novel compounds.From the EtOAc soluble fraction of 60% EtOH extract of the lianas of G. pendulum, 11 compounds were isolated, and 4 of them were new ones. The structures were identified as: gnetupendins A-D (1-4), isorhapontigenin (5),resveratrol (6),daucosterol (7),shegansu B (8),gnetulin (9),gnetin D (10),isorhapontigenin -3-O-β-D-glucoside (11). Their structures were characterized unambiguously on the basis of chemical and spectroscopic evidence. Gnetupendins A and B were new stilbenes with novel skeletons, with the 3, 5-dihydroxyl- benzene ring substituted by a benzyl group, this skeleton has never been reported before. Gnetupendin C was a new stilbene dimer coupled by a resveratrol and an oxyresveratrol with a cis dihydrobenzofuran obtained from nature for the first time, gnetupendin D was the first isorhapontigenin dimer glucoside obtained from nature.From the lianas of G. montanum f. megalocarpum, 21 compounds were obtained by systematic isolation, 20 of them were identified, 4 of them were new compounds named as gnetumontanins A-D (1-4), and the known compounds were determined to be: pinosylvin (5),apigenin (6),gnetifolin A (7),p-coumaric acid (8), isorhapontigenin (9),resveratrol (10),gnetol (11),gnetupendin B (12),daucosterol (13),shegansu B (14),(-)-ε-viniferin (15),gnetulin (16),gnetin D (17),gnetuhainin M (18),isorhapontigenin-3-O-β-D-glucoside (19),isorhapontigenin-12-O-β-D-glucoside (20) . Gnetumontanin A is the first oligostilbene dimerized by two oxyresveratrol units with dihydrobenofuran ring; gnetumontanin B is a new stilbene trimer polymerized by two oxyresveratrol and one resveratrol units with two dihydrobenofuran rings; gnetumontanin C is a new stilbenoid with a novel skeleton including aδ-lactone portion and gnetumontanin D is a glucoside of it.From the lianas of G. hainansene, some oligostilbenes polymerized by different monomer were obtained, in order to study biomimetic synthesis and seek for more leading compounds, oxidative coupling reaction were performed by the different bioactive monomer resveratrol and isorhapontigenin. After separation and purification, 9 compounds were obtained and 8 of them were new. The structures were determined as: Fe-2,ε-viniferin, a known compound, is a dimer of resveratrol. Fe-3 and Fe-4 are both new dimers of resveratrol and isorhapontigenin. Fe-5, Fe-7, Fe-8, Fe-9 are new trimers polymerized by isorhapontigenin and resveratrol units. Fe-6 is a new symmetrical dimer of isorhapontigenin. Fe-3～Fe-10 are all new compounds. The structure of Fe-7 has the ampelopsinic skeleton, and the structures of Fe-8～Fe-10 has two dihydrobenzofuran rings with symmetry. These skeletons were reported for the first time in the biomimetic synthesis.From the literatures, prenyl group is reported to be a group with muti-faceted bioactivity, in order to polymerize oligomeric stilbenes with prenylated groups, a series of prenylated stilbene monomers were semi-synthesized from resveratrol and isorhapontigenin respectively. Under the basic conditions, prenyl group was inducted to the structure of resveratrol, and a series of prenylated derivatives were obtained. After isolation by silica gel column chromatography, 12 compounds were determined, among them, 11 were new and 1 was a known naturally occurring compound. The regular of prenyl group induction to resveratrol was concluded. Catalyzed by Lewis acid, prenyl group was inducted to the structure of isorhapontigenin. Alter separation, 3 new compounds were determined. Polymerization experiment of the high-yielded compound was executed to obtain 2 stilbene dimers with two prenyle groups.In order to evaluate the Structure-Activity relationship, a series of shegansu B derivatives were semi-synthesized.Meanwhile, a comprehensive investigation on formic acid catalyzed polymerization of oligostilbene was studied. A special reaction losing two substituted benzene rings and a methoxyl group successively during Diels-Alder reaction was found.32 compounds were produced by the biomimetic experiment.For the obtained naturally occurring and semi-synthesized oligostilbenes (including the intermediate compounds), the pharmacological activities were evaluated on anti-oxidative, anti-inflammatory, anti-HIV and anti-tumour activities, respectively and valuable experimental data were obtained about the Structure-Activity relationship.