Isolation and characterization of aphidicolin and chlamydosporol derivatives from Tolypocladium inflatum

Six new secondary metabolites including two aphidicolin analogues, inflatins A (1) and B (2), and four chlamydosporol derivatives, inflatins C-F (3-6), have been isolated from the crude extract of Tolypocladium inflatum. The structures of 1-6 were determined mainly by NMR experiments, and 4 and 5 were further confirmed by X-ray crystallography. The absolute configurations of C-16 in 1 and C-5 in 3 were deduced via the circular dichroism data of the in situ formed [Rh?(OCOCF?)?] complexes, whereas that of 4 was assigned by X-ray crystallography using Cu Kα radiation. Compounds 1 and 2 showed modest cytotoxicity against a panel of eight human tumor cell lines.     

Anxiolytic effect of natural galphimines from Galphimia glauca and their chemical derivatives

The anxiolytic effects of galphimine B (1), galphimine A (2), and galphimine E (3), natural nor-secofriedelanes isolated from Galphimia glauca, as well as derivatives obtained by acetylation (4), hydrogenation of the C-1/C-2 double bond (5), basic hydrolysis followed by hydrogenation of the C-1/C-2 double bond (6), and deacetylation (7) of galphimine E (3), were evaluated on ICR mice exposed to the elevated plus-maze test. This study also included the evaluation of a galphimines-rich fraction (GRF) with a known concentration of 1-3, obtained from the dry leaves of G. glauca. Intraperitoneal administration of 15 mg/kg of 1, 2, 6, and GRF (1 h before testing) caused an anxiolytic-like effect in the animals, increasing significantly (p <0.001) the percentage of time of permanence and the number of crossings toward the open arms of the plus-maze. No activity was detected after administration of compounds 3, 4, 5, and 7. These results showed that GRF had activity similar to the most active pure galphimines (1 and 2) and that, like for the spasmolytic activity previously reported, the main determining factor responsible for the anxiolytic activity of the compounds was the presence of free hydroxyl groups at C-4, C-6, and C-7 and the presence of the double bond in the A ring.     

N-hydroxypyridones, phenylhydrazones, and a quinazolinone from Isaria farinosa

New N-hydroxypyridones, militarinones E (1) and F (2), phenylhydrazones, farylhydrazones A (3) and B (4), a quinazolinone, 2-(4-hydroxybenzyl)quinazolin-4(3H)-one (5), and the known militarinones A (6) and B (7) were isolated from cultures of the Cordyceps-colonizing fungus Isaria farinosa. The structures of 1-5 were elucidated by spectroscopic methods, and 3 was confirmed by X-ray crystallography. The absolute configuration of the C-4' secondary alcohol in 1 was deduced via the circular dichroism data of the in situ formed [Rh(2)(OCOCF(3))(4)] complex. Compounds 1 and 6 showed significant cytotoxicity against A549 cells, whereas 7 was active against Staphylococcus aureus, Streptococcus pneumoniae, and Candida albicans.     

Cytotoxic acylated triterpene saponins from the husks of Xanthoceras sorbifolia

Four new oleanane-type triterpene saponins, xanifolia-Y0 (1), xanifolia-Y2 (2), xanifolia-Y3 (3), and xanifolia-Y7 (4), were isolated from the husks of Xanthoceras sorbifolia along with two known analogues, xanifolia-Y8 (5) and xanifolia-Y10 (6). The structures of 1-4 were determined by spectroscopic data interpretation and chemical degradation. Compounds 1-6 were evaluated for their cell-growth inhibition activity toward human ovarian cancer cells (OVCAR3) by a MTT assay, and the IC50 values ranged from 4 to 13 microM. On the basis of the results obtained, it is concluded that a C-3 trisaccharide with a galactose and acylation with an angeloyl group at both C-21 and C-22 are important for cell inhibition activity for this class of compounds.     

Isolation and characterization of miscellaneous secondary metabolites of Deprea subtriflora

Two new C-18 norwithanolides based on a C(27) skeleton, subtrifloralactones K (1) and L (2), a new C-18 oxygenated withanolide, 13 beta-hydroxymethylsubtrifloralactone E (3), and a new alpha-ionone derivative, (+)-7 alpha,8 alpha-epoxyblumenol B (4), along with five known compounds, philadelphicalactone A (5), (2S,3S,4R)-2-[(2R)-2'-hydroxytetracosanoylamino]-1,3,4-octadecanetriol (6), trans-N-feruloyltyramine, cis-N-feruloyltyramine, and (S)-coriolic acid, were isolated from additional active fractions of the chloroform-soluble extract of Deprea subtriflora, using a quinone reductase (QR) induction assay as a monitor. The structures of compounds 1-4 were characterized by spectroscopic data interpretation. The potential cancer chemopreventive activities of all isolates in terms of their ability to induce QR activity with cultured Hepa 1c1c7 mouse hepatoma cells were evaluated.     

Bioactive quassinoids from the seeds of Brucea javanica

Six new quassinoids (1-6) and eight known compounds of this type (7-14) were isolated from the seeds of Brucea javanica. Their structures were elucidated by analysis of their spectroscopic data and from chemical evidence. Compounds 1-5 were found to be unusual quassinoids with a 2,3-seco A ring. The configurations at C-4 in 4 and 5 were determined by a difference circular dichroism method. In in vitro bioassays, 8 and 10 showed inhibitory activities for nitric oxide production in LPS-activated macrophages, with IC(50) values of 1.9 and 5.0 μM, respectively, while compounds 6, 8-11, 13, and 14 exhibited cytotoxicity against five human tumor cell lines (HCT-8, HepG2, BGC-823, A549, and SKVO3), having IC(50) values in the range 0.12-9.3 μM.     

Cytotoxic constituents of Aspergillus terreus from the rhizosphere of Opuntia versicolor of the Sonoran Desert

A novel cyclopentenedione, asterredione (1), two new terrecyclic acid A derivatives, (+)-5(6)-dihydro-6-methoxyterrecyclic acid A (2) and (+)-5(6)-dihydro-6-hydroxyterrecyclic acid A (3), and five known compounds, (+)-terrecyclic acid A (4), (-)-quadrone (5), betulinan A (6), asterriquinone D (7), and asterriquinone C-1 (8), were isolated from Aspergillus terreus occurring in the rhizosphere of Opuntia versicolor, using bioassay-guided fractionation. Acid-catalyzed reaction of 2 under mild conditions afforded 4, whereas under harsh conditions 2 yielded 5 and (-)-isoquadrone (9). Catalytic hydrogenation and methylation of 4 afforded 5(6)-dihydro-terrecyclic acid A (10) and (+)-terrecyclic acid A methyl ester (11), respectively. The structures of 1-11 were elucidated by spectroscopic methods. All compounds were evaluated for cytotoxicity in a panel of three sentinel cancer cell lines, NCI-H460 (non-small cell lung cancer), MCF-7 (breast cancer), and SF-268 (CNS glioma), and were found to be moderately active. Cell cycle analysis of 2, 4, and 5 using the NCI-H460 cell line indicated that 4 is capable of disrupting the cell cycle through an apparent arrest to progression at the G(1) and G(2)/M phases in this p53 competent cell line. A pathway for the biosynthetic origin of asterredione (1) from asterriquinone D (7) is proposed.     

Inhibitors of bacterial multidrug efflux pumps from the resin glycosides of Ipomoea murucoides

A reinvestigation of the CHCl 3-soluble extract from flowers of the Mexican medicinal arborescent morning glory, Ipomoea murucoides, through preparative-scale recycling HPLC, yielded six new pentasaccharides, murucoidins VI-XI (1- 6), as well as the known pescaprein III (7), stoloniferin I (8), and murucoidins I-V (9- 13). Their structures were characterized through the interpretation of their NMR spectroscopic and FABMS data. Compounds 1-6 were found to be macrolactones of three known glycosidic acids identified as simonic acids A and B, and operculinic acid A, with different fatty acids esterifying the same positions, C-2 on the second rhamnose unit and C-4 on the third rhamnose moiety. The lactonization site of the aglycone was placed at C-2 or C-3 of the second saccharide unit. The esterifying residues were composed of two short-chain fatty acids, 2-methylpropanoic and (2S)-methylbutyric acids, and two long-chain fatty acids, n-dodecanoic (lauric) acid and the new (8R)-(-)-8-hydroxydodecanoic acid. For the latter residue, its absolute configuration was determined by analysis of its Mosher ester derivatives. All members of the murucoidin series exerted a potentiation effect of norfloxacin against the NorA overexpressing Staphylococcus aureus strain SA-1199B by increasing the activity 4-fold (8 microg/mL from 32 microg/mL) at concentrations of 5-25 microg/mL. Stoloniferin I (8) enhanced norfloxacin activity 8-fold when incorporated at a concentration of 5 microg/mL. Therefore, this type of amphipathic oligosaccharide could be developed further to provide more potent inhibitors of this multidrug efflux pump.     

Hypoglycemic diterpenoids from Tinospora crispa

Three new diterpenoids, 2-O-lactoylborapetoside B (1), 6'-O-lactoylborapetoside B (2), and tinocrispol A (3), and nine known diterpenoids (4-12) were isolated from an EtOH extract of Tinospora crispa vines. Their structures were elucidated by spectroscopic analyses. The C-6 glucosyloxy group in borapetoside C (6) was revised to be α-oriented. The in vivo hypoglycemic activities of the major components, borapetosides A-C (4-6), were examined. Intraperitoneal injection of 4 and 6 (5 mg/kg) showed significant lowering of plasma glucose levels in normal and streptozotocin-induced type 1 diabetic mice. Borapetoside C increased glucose utilization in peripheral tissues and reduced hepatic gluconeogenesis, accounting for the hypoglycemic effect.     

轮叶棘豆的化学成分研究

目的：研究轮叶棘豆的化学成分。方法：90%乙醇冷浸提取,所得浸膏经硅胶,聚酰胺,C-18,Sephadex LH-20等多种材料进行柱色谱分离,通过波谱学方法鉴定化合物的结构。结果：分离鉴定了8个化合物,分别鉴定为azukisapogenol(1),(22E,24R)-24-甲基-5α-胆甾-7,22-二烯-3β,5α,6β-三醇(2),芹菜素(3),3′,4′-二甲氧基-槲皮素-3-O-β-D-半乳糖吡喃苷 (4),7,4′- 二甲氧基-槲皮素-3-O-α-L-鼠李糖吡喃基(1→2)-β-D-葡萄糖吡喃苷(5),(2S,3S,4R)-N-［(R)-2′-羟基二十四烷醇基］-1,3,4-三羟基-2-氨基-十八-6-烯(6),β-谷甾醇(7),胡萝卜苷(8)。结论：所有化合物均为首次从该植物中分得。     

Nigerapyrones A-H, α-pyrone derivatives from the marine mangrove-derived endophytic fungus Aspergillus niger MA-132

Eight new α-pyrone derivatives, namely, nigerapyrones A-E (1-5) and nigerapyrones F-H (8-10), along with two known congeners, asnipyrones B (6) and A (7), were isolated from Aspergillus niger MA-132, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Avicennia marina. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The undescribed geometries of the trisubstituted double bonds (C-9 and C-11) for asnipyrone B (6) have now been explicitly determined, while the incorrect placement of the methyl group at C-5 of asnipyrone A (7) has now been revised at C-3. The cytotoxic activities of the isolated α-pyrone derivatives against eight tumor cell lines as well as antimicrobial activities against two bacteria and four plant-pathogenic fungi of these compounds were evaluated. Compounds 2, 4, 5, and 7 showed weak cytotoxicity against some of the tested tumor cell lines.     

Anthelmintic polyfunctional nitrogen-containing terpenoids from marine sponges

The study of the anthelmintic terpenoid components from the Fiji sponge Axinyssa fenestratus (senior synonym of Leucophloeus fenestratus) and two Thailand sponges, Acanthella cavernosa and Topsentia sp., has yielded several new nitrogen-containing sesqui- and diterpenes of known carbon skeletons. Amorphane sesquiterpenes from A. fenestratus included (1R, 6S, 7S, 10S)-10-isothiocyanato-4-amorphene [(+)-1] and new metabolites (1R*, 4S*, 6R*, 7S*)-4-isothiocyanato-9-amorphene [2], 10-isothiocyanato-4,6-amorphadiene [3], and (4S*, 10S*)-10-isothiocyanato-5-amorphen-4-ol [4]. The amorphene (+)-1 of this study may be antipodal to (-)-1 previously isolated from a Hawaiian sponge. A similar relationship may exist at C-1, C-6, C-7 between (+)-2 of this study and (-)-11 isolated from a Palauian sponge. Another known sesquiterpene, axisonitrile 3 [5] was obtained from Topsentia sp. The diterpenes obtained from A. cavernosa included known kalihinols X [6] and Y [8] and new kalihinols J [7] and I [9]. Those terpenoids with potent antiparasite activity include 1, 2, 3-5, and 7-9.     

1-deoxypaclitaxel and abeo-taxoids from the seeds of Taxus mairei

A new paclitaxel derivative and two new 2(3-->20)-abeo-taxoids were isolated from a methanol extract of the seeds of Taxus mairei, and their structures were established as 1-deoxypaclitaxel (1), 7beta,10beta-diacetoxy-2alpha,5alpha,13alpha-trihydroxy-2(3-->20)-abeo-taxa-4(20),11-dien-9-one (2), and 2alpha,13alpha-diacetoxy-10beta-hydroxy-2(3-->20)-abeo-taxa-4(20),6,11-triene-5,9-dione (3) on the basis of spectroscopic data analysis. Taxane 1 is the first example of a paclitaxel analogue with a C-1beta hydrogen substituent. Taxane 3 is an 2(3-->20)-abeo-taxane with a rare C-5 ketone and C-6 double bond.     

Lepadins F-H, new cis-decahydroquinoline alkaloids from the Australian ascidian Aplidium tabascum

Chemical investigation of a Great Barrier Reef ascidian, Aplidium tabascum, has resulted in the isolation of three new cis-decahydroquinoline alkaloids, lepadins F-H (4-6). The three new compounds differ from the previously isolated lepadins A-C (1-3) in that they contain a fully saturated 5-hydroxyoctyl side chain attached at C-5, an unsaturated eight-carbon ester moiety attached to C-3, and opposite stereochemistry at C-5 and C-3. Lepadins G (5) and H (6) are epimers at C-2. NMR and molecular modeling studies indicated that the three new compounds adopt a chair-chair conformation in which the nitrogen equatorially substitutes the cyclohexyl ring. This contrasts with lepadins A-C (1-3), which adopt a chair-chair conformation in which the nitrogen axially substitutes the cyclohexyl ring.     

Tetranortriterpenoids from Cipadessa baccifera

Five new mexicanolide-type tetranortriterpenoids, tigloylseneganolide A (1), 2'R-methylbutanoylproceranolide (2), 2'S-methylbutanoylproceranolide (3), 2'R-cipadesin A (4), and 2'R-cipadesin (6), as well as the known 2'S-epimers of 4 and 6 (5 and 7), together with six other known limonoids, were isolated from the seeds of Cipadessa baccifera. The structures of these compounds were elucidated on the basis of spectroscopic analyses and chemical methods. 1H NMR-based conformational analysis was applied to establish the absolute configuration of the sterically hindered 2-methylbutanoyl in three epimeric pairs (2-7). A general rule for the determination of the absolute configurations of 2R- and 2S-methylbutanoyl groups at C-3 of a limonoid in a mixture is proposed.     

Biotransformation of the fungistatic sesquiterpenoid patchoulol by botrytis cinerea

Biotransformation of the fungistatic sesquiterpenoid patchoulol (1) by the fungus Botrytis cinerea affords the 5-, 7- and (8R)-hydroxy (2, 3, and 5) derivatives as the major metabolites, together with a number of minor metabolites (4, 6-9) arising from hydroxylation at C-2, C-3, C-5, C-9, C-13, and C-14.     

New indole alkaloids from the bark of Nauclea orientalis

Four new alkaloids, nauclealines A (1) and B (2) and naucleosides A (3) and B (4), together with six known compounds, strictosamide (5), vincosamide (6), pumiloside (7), kelampayoside A, sitosterol, and sitosteryl beta-D-glucoside, were isolated from the bark of Nauclea orientalis. The structures of 1-4 were elucidated using 1D and 2D NMR spectral methods, including COSY, DEPT, HMQC, (13)C-(1)H HMBC, and (15)N-(1)H HMBC.     

Terpenoids Produced by Actinomycetes: Napyradiomycins from Streptomyces antimycoticus NT17

Napyradiomycin SR ( 1), 16-dechloro-16-hydroxynapyradiomycin C2 ( 2), 18-hydroxynapyradiomycin A1 ( 3), 18-oxonapyradiomycin A1 ( 4), 16-oxonapyradiomycin A2 ( 5), 7-demethyl SF2415A3 ( 6), 7-demethyl A80915B ( 7), and ( R)-3-chloro-6-hydroxy-8-methoxy-alpha-lapachone ( 8) were isolated from the culture broth of Streptomyces antimycoticus NT17. These compounds are derivatives of the napyradiomycins isolated previously from Chainia rubra or Streptomyces aculeolatus. The structures of the new compounds, some of which exhibit antibacterial activities, were established by comparing their NMR data with data of related known compounds. The unique structure of 1, containing a highly strained ring, was established by NMR and was confirmed by X-ray analysis. Two of the compounds are C-16 stereoisomers of napyradiomycin A2 and are named napyradiomycins A2a ( 9a) and A2b ( 9b).     

New beta-caryophyllene-derived terpenoids from the soft coral Sinularia nanolobata

Two new norsesquiterpenoids, nanonorcaryophyllenes A (1) and B (2), two new diterpenoids, nanolobatins A (3) and B (4), and a novel norditerpenoid, nanolobatin C (5), were isolated from the n-hexane extract of the Taiwanese soft coral Sinularia nanolobata. Also, two new furanone derivatives, 6 and 7, were isolated for the first time from natural sources. The structures of 1-5 were elucidated on the basis of extensive spectroscopic analyses and by comparison of the spectral data with those of the related metabolites. Nanonorcaryophyllenes A (1) and B (2) were characterized as 13-norcaryophyllenes that lack a methyl group at C-11, while nanolobatin C (5) represents the first example of a xeniaphyllane-based 17-norditerpenoid. The cytotoxicity of 1-6 against the growth of a limited panel of cancer cell lines is also described.     

Ipomoeassins A-E, cytotoxic macrocyclic glycoresins from the leaves of Ipomoea squamosa from the Suriname rainforest

The new glycoresins, ipomoeassins A-E (1-5), have been isolated from the leaves of Ipomoea squamosa. The structures were elucidated by spectroscopic analyses and chemical transformations. The absolute configurations of C-5 (ipomoeassins 3-5) and C-11 (ipomoeassins 1 and 2) were determined by their derivatives with (R)- and (S)-MPA. All the isolates were active in the A2780 human ovarian cancer cell line assay, and 4 showed the highest activity with an IC(50) value of 35 nM.