Two new sesquiterpenes from Artemisia annua L.

Investigation of the dried whole plants of Artemisia annua led to the isolation of two new sesquiterpenes, artemanins A (1) and B (2), along with twenty-nine known compounds. The structures of the new compounds were elucidated by spectroscopic and chemical means.

[Diversity of Secondary Metabolites from Some Medicinal Plants and Cultivated Lichen Mycobionts].

Studies on the structural determination, biosynthesis, and biological activities of secondary metabolites from natural sources are significant in the field of natural products chemistry. This review focuses on diverse secondary metabolites isolated from medicinal plants and cultivated mycobionts of lichens in our laboratory. Monoterpene-tetrahydroisoquinoline glycosides and alkaloids isolated from Cephaelis acuminata and Alangium lamarckii gave important information on the biosynthesis of ipecac alkaloids. A variety of glycosides linked with a secologanin unit and indole alkaloids were obtained from medicinal plants belonging to the families of Rubiaceae, Apocynaceae, and Loganiaceae. Plant species of the four genera Fraxinus, Syringa, Jasminum, and Ligustrum of the family Oleaceae were chemically investigated to provide several types of secoiridoid and iridoid glucosides. The biosynthetic pathway leading from protopine to benzophenanthridine alkaloids in suspension cell cultures of Eschscholtzia californica was elucidated. The structures and biological activities of the bisbenzylisoquinoline alkaloids of Stephania cepharantha and Nelumbo nucifera were also investigated. In addition, the mycobionts of lichens were cultivated to afford various types of metabolites that differ from the lichen substances of intact lichens but are structurally similar to fungal metabolites. The biosynthetic origins of some metabolites were also studied. These findings suggest that cultures of lichen mycobionts could be sources of new bioactive compounds and good systems for investigating secondary metabolism in lichens.

Polyprenylated Benzoylphloroglucinols with DNA Polymerase Inhibitory Activity from the Fruits of Garcinia schomburgkiana.

Chemical investigation of the fruits of Garcinia schomburgkiana collected in Vietnam led to the isolation of eight new schomburgkianones, A-H (1-8), four known (9-12) polyprenylated benzoylphloroglucinols, and four known biflavonoids. The structures of these compounds were elucidated by spectroscopic and chemical means. The absolute configuration at C-40 of 1 and 2 was determined by (1)H NMR analyses of their MPA esters. The configuration of the bicyclo[3.3.1]nonane core of the polyprenylated benzoylphloroglucinols was assigned by comparison of their experimental ECD spectra with those of related compounds. The polyprenylated benzoylphloroglucinols exhibited inhibitory activities against mammalian DNA polymerases α and λ, with IC50 values ranging from 5.0 to 8.8 µM. Compounds 1, 2, 4, 5, and 9-11 showed cytotoxic effects against HeLa human cervical cancer cells with median lethal dose values lower than 10 µM.

Alkaloids from the Tuber of Stephania cf. rotunda.

Chemical investigation of the tuber of Stephania cf. rotunda collected in Vietnam led to the isolation of a new stephaoxocane-type alkaloid, stepharotudine (1), twenty -eight known alkaloids, and two known amides. The chemical structures of the isolated compounds were determined by spectroscopic and chemical methods. The absolute configuration of the new compound was determined from its CD spectrum and by 1H NMR analyses of its MPA esters. For the known alkaloids ()crebanme-ß-N-oxide (2), uthongine (3), and palmatrubine (4), fully assigned NMR data are also reported for the first time.

Serotonergic mechanisms are involved in antidepressant-like effects of bisbenzylisoquinolines liensinine and its analogs isolated from the embryo of Nelumbo nucifera†Gaertner seeds in mice.

OBJECTIVES: We attempted to ascertain if bisbenzylisoquinoline alkaloids, liensinine and isoliensinine from Nelumbo nucifera Gaertner have antidepressant-like effects and compare the effects with those previously obtained by their analogue neferine. METHODS: Using mice, the forced swimming test (FST) was carried out after treatment with liensinine, isoliensinine and neferine. KEY FINDINGS: Liensinine and isoliensinine elicited antidepressant-like effects in mice after the FST. Anti-immobility effects of liensinine and isoliensinine were antagonized by the 5-hydroxytryptamine1 A (5-HT1 A ) receptor antagonist WAY 100635, but not by the α1 -adrenoceptor antagonist prazosin. The anti-immobility effects of liensinine, isoliensinine and neferine were blocked by pretreatment with p-chlorophenylalanine (PCPA), which depletes serotonin (5-HT). CONCLUSIONS: These data suggest that liensinine and isoliensinine from Nelumbo nucifera Gaertner have antidepressant-like effects and that antidepressant-like effects of liensinine and its analogues are closely related to serotonergic mechanisms.

Three acetophenones from Acronychia pedunculata.

Phytochemical investigation of the leaves and twigs of Acronychia pedunculata has led to the isolation of three new acetophenone monomers 1-3 as well as 1-[2',4'-dihydroxy-3',5'-di-(3″-methyl-2″-butenyl)-6'-methoxy]phenylethanone (4), acronyculatin E (5), a mixture of ß-sitosterol and stigmasterol, and sesamin. The structures of these new compounds were elucidated spectroscopically. The inhibitory activities of the isolated acetophenone derivatives against mammalian DNA polymerases and human cancer cell growth were also assessed.

Synthesis and pharmacological activity of alkaloids from embryo of lotus, Nelumbo nucifera.

Bisbenzylisoquinoline alkaloid, nelumboferine which was recently isolated from the embryo of Nelumbo nucifera, and stereoisomers of neferine, which is a major alkaloid of the embryo of N. nucifera, were stereoselectively synthesized. Pharmacological activity of nelumboferine, stereoisomers of neferine, liensinine, isoliensinine, and O-methylneferine were evaluated.

Bisbenzylisoquinoline Alkaloids from Nelumbo nucifera.

From the embryos of the seeds of Nelumbo nucifera, three bisbenzylisoquinoline alkaloids, nelumboferine and nelumborines A and B, were isolated along with four known compounds, neferine, liensinine, isoliensinine and anisic acid. The structures of the new alkaloids were determined mainly by spectroscopic methods.

Secoiridoid glucosides and unusual recyclized secoiridoid aglycones from Ligustrum vulgare.

Phytochemical investigation of the dried leaves and twigs of Ligustrum vulgare has led to the isolation of the secoiridoid glucosides, (2''R)- and (2''S)-10-hydroxy-2''-methoxyoleuropeins (1 and 2), and the secoiridoid aglycones, ligustrohemiacetals A (3) and B (4). Their structures were elucidated by spectroscopic and chemical means. Enzymatic hydrolysis of 10-hydroxyoleuropein to the analog of ligustrohemiacetals A and B led to the structural revision of jasmolactones.

Effects of extracts and neferine from the embryo of Nelumbo nucifera seeds on the central nervous system.

The effects of embryos of the seeds of Nelumbo nucifera on the central nervous system were studied in mice. MeOH extracts of embryos of Nelumbo nucifera seeds significantly inhibited locomotor activity in mice. The MeOH extract was successively partitioned between H(2)O and n-hexane, between H(2)O and CHCl(3), and between H(2)O and n-BuOH. CHCl(3) extracts strongly inhibited locomotor activity in mice, although other extracts had no effect on locomotor activity. The main alkaloid of CHCl(3) extracts, neferine, dose-dependently inhibited locomotor activity in mice. Neferine induced hypothermia in mice and apparently potentiated thiopental-induced sleeping time. An anxiolytic, diazepam, decreased locomotor activity, rectal temperature and enhanced sleep elicited by thiopental, similar to neferine. In addition, neferine and diazepam showed anti-anxiety effects in the elevated plus maze test. Neferine did not affect muscle coordination by the rota-rod test. Neferine did not affect strychnine- nor picrotoxin-induced seizure. In contrast, diazepam had apparent muscle relaxant and anti-convulsant effects. These results suggest that neferine has several central effects and that neferine may participate in the efficacy of the sedative effects of embryos of the seeds of Nelumbo nucifera. The mechanisms of the sedative effects of neferine are not similar to those of diazepam.

Secoiridoid glucosides from Strychnos spinosa.

Three new secoiridoid glucosides, stryspinoside (1) and strychosides A (2) and B (3), were isolated, together with 23 known compounds, from the dried branches of Strychnos spinosa. The structures of the new compounds were determined by spectroscopic means.

Indole alkaloids and other constituents of Rauwolfia serpentina.

From the dried roots of Rauwolfia serpentina were isolated five new indole alkaloids, N(b)-methylajmaline (1), N(b)-methylisoajmaline (2), 3-hydroxysarpagine (3), yohimbinic acid (4), isorauhimbinic acid (5), a new iridoid glucoside, 7-epiloganin (6), and a new sucrose derivative, 6'-O-(3,4,5-trimethoxybenzoyl)glomeratose A (7), together with 20 known compounds. The structures of the new compounds were determined by spectroscopic and chemical means. The inhibitory activities of the selected alkaloids on topoisomerase I and II and their cytotoxicity against the human promyelocytic leukemia (HL-60) cell lines were assessed.

Six secoiridoid glucosides from Adina racemosa.

Six novel secoiridoid glucosides, adinosides A (1), B (2), C (3), D (4), E (5), and grandifloroside 11-methyl ester (6) were isolated, together with 27 known compounds, from the dried leaves, flowers, and twigs of Adina racemosa. The structures of the new compounds were determined by spectroscopic (NMR, MS) and chemical means.

Phenyl ethers from cultured lichen mycobionts of Graphis scripta var. serpentina and G. rikuzensis.

Spore-derived mycobionts of the lichen Graphis scripta var. serpentina and G. rikuzensis were cultivated on a malt-yeast extract medium supplemented with 10% sucrose and their metabolites were investigated. 3,3'-Dihydroxy-5,5'-dimethyldiphenyl ether was isolated from the cultures of the mycobionts of G. scripta var. serpentina, while a new phenyl ether, rikuzenol, along with two known diphenyl ethers, violaceol-I and violaceol-II, were isolated from those of G. rikuzensis. The structure of the new compound was determined by spectroscopic methods. Violaceol-I was chemically synthesized and interconversion between violaceol-I and violaceol-II was proven.

Flavonoid glycosides from Rhazya orientalis.

Six new flavonoid glycosides, quercetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (1), quercetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(3-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (2), isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (3), isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(3-O-trans-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (4), isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-cis-p-coumaroyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (5), and isorhamnetin 3-O-alpha-L-rhamnopyranosyl(1-->6)-[alpha-L-rhamnopyranosyl(1-->2)]-(4-O-trans-feruloyl)-beta-D-galactopyranoside-7-O-alpha-L-rhamnopyranoside (6), were isolated from the dried aerial parts of Rhazya orientalis. The structures of 1-6 were determined by spectroscopic and chemical means.