Search

Nine triterpene saponins, acutangulosides A−F (2−7), and acutanguloside D−F methyl esters (5a−7a) and a single triterpene aglycone (1) were isolated from a water extract of the bark of Barringtonia acutangula. Their structures were assigned on the basis of spectroscopic data.

Three new marine natural products, dysinosins B−D (1−3), were isolated from the sponge Lamellodysidea chlorea and their structures determined by 1D and 2D NMR spectroscopy. These compounds are inhibitors of the blood coagulation cascade serine proteases factor VIIa and thrombin. These analogues, dysinosins B−D (1−3), allowed identification of two structural motifs within the structures that contribute to binding to the proteases, factor VIIa and thrombin.

Naturally occurring cembranes 1−4 have been isolated from a Sarcophyton sp. These compounds have not previously been found to occur in nature but had been obtained as intermediates in a synthetic modification from tobacco. The absolute stereochemistries of 3 and 4 were determined. Compounds 1 and 2 inhibited the binding of [³H]8-cyclopentyl-1,3-dipropylxanthine to rat-brain adenosine A1 receptors.

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.

Four cheilanthane sesterterpenoids, 25-hydroxy-13(24),15,17-cheilanthatrien-19,25-olide (1), 13,16-epoxy-25-hydroxy-17-cheilanthen-19,25-olide (2), 25-hydroxy-13(24),17-cheilanthadien-16,19-olide (3), and 16,25-dihydroxy-13(24),17-cheilanthadien-19,25-olide (4), were isolated from the marine sponge Ircinia sp. Compounds 1, 3, and 4 are new natural products. The four compounds inhibit MSK1 (mitogen and stress activated kinase) and MAPKAPK-2 (mitogen activated protein kinase activated protein kinase), two protein kinases involved in mitogen and stress signal transduction.

The combined CH2Cl2 and MeOH crude extract of a new species of the marine sponge Dysidea, collected in Northern Australia was found to inhibit the binding of [I125] interleukin-8 [IL-8] to the human recombinant IL-8 receptor type A at 500 μg/mL. Bioassay-guided fractionation led to the isolation of three new polyoxygenated sterols 3, 4, and 5. Their structures were assigned on the basis of 1D and 2D NMR experiments, and relative stereochemistries were established by ROESY correlations and analysis of coupling constants. The IC50 values for inhibition of IL-8Ra for sterols 3, 4, and 5 were 20, 5.5, and 4.5 μM, respectively.

The Australian sea pen Anthoptilum cf. kukenthali has afforded five new briarane-type diterpenes, anthoptilides A−E. Their structures were determined on the basis of their spectroscopic data. Single-crystal X-ray determination was performed on anthoptilide A. Anthoptilides B and C inhibited the binding of [³H]1,3-dipropyl-8-cyclopentylxanthine ([³H]DPCPX) on adenosine A1 receptors.

Chemical investigation of a Great Barrier Reef ascidian, Aplidium longithorax has resulted in the isolation of two new para-substituted cyclofarnesylated hydroquinone compounds, longithorols C (1) and D (2), and a novel macrocyclic chromenol, longithorol E (3). Longithorol C (1) had its absolute stereochemistry determined by the advanced Mosher method and all compounds had their structures determined by interpretation of spectroscopic data.

The CH2Cl2 extract of the marine sponge Xestospongia testudinaria inhibited [³H]DPCPX binding to rat-brain adenosine A1 receptors. Bioassay-guided fractionation led to the isolation of a known brominated acetylenic fatty acid 1 as the active component. Also isolated were two novel sterol esters 2 and 3. All structures were determined on the basis of their spectroscopic data.

Five novel lamellarin-class alkaloids have been isolated from a Great Barrier Reef ascidian, Didemnum chartaceum. The structures of the 20-sulfated derivatives of lamellarins B, C, and L (1−3); the 8-sulfated derivative of lamellarin G (4), plus a nonsulfated compound, lamellarin Z (5), were identified by interpretation of spectroscopic data. Lamellarin G 8-sulfate (4) is the first example of this class of compounds sulfated at the C-8 position, while lamellarin Z (5) is the first example of a dimethoxylated lamellarin. The known lamellarins A, B, C, E, G, and L (6−11), plus the triacetate derivatives of lamellarins D (12) and N (13), were also isolated. An aberration in the integration of signals in the ¹H NMR spectra of the 20-sulfated derivatives of lamellarins B, C, and L (1−3) led to NMR relaxation studies. T1 values were calculated for all protons in the sulfated lamellarins (1−4) and their corresponding nonsulfated derivatives (7, 8, 10, 11). Interestingly, the protons ortho to the sulfate group in compounds (1−4) had T1 values up to five times larger than the corresponding protons in their nonsulfated derivatives (7, 8, 10, 11).

A series of 12 substituted 1-phenylpyrazolo[3,4-d]pyrimidines were synthesized and evaluated for rat brain adenosine A1 and A2a receptor binding affinity. Substituents at C-4 and C-6 were varied in order to define these regions in terms of molecular recognition by the receptor subtypes. At C-4, the effects of a mercapto, methylthio, and amino substituent were evaluated, while at C-6, amides with varying alkyl groups extending from the α-carbon were examined. This study identified both potent and selective adenosine A1 receptor antagonists. The most potent of the 12 compounds was α-[(4-amino-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl)thio]hexanamide (14); with an A1 Ki of 0.939 nM and an A2a Ki of 88.3 nM, this compound is 94-fold A1 selective. The most selective of the 12 compounds was α-[[4-(methylthio)-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl]thio]hexanamide (10); with an A1 Ki of 6.81 nM and an A2a Ki > 40 000 nM, this compound is >5900-fold A1 selective. The structure−activity relationships for the complete series has identified discrete structural differences between the A1 and A2a receptors with respect to the binding of pyrazolo[3,4-d]pyrimidines. This study resulted in prediction that increased A1 affinity could be achieved by incorporation of NH-alkyl substituents at C-4. This was confirmed by synthesis of α-[[4-(methylamino)-1-phenylpyrazolo[3,4-d]pyrimidin-6-yl]thiol]hexanamide (15) which was found to have an A1 Ki of 0.745 nM.

Bioassay-guided fractionation of the MeOH extract of the sponge Oceanapia sp. using the Helicobacter pylori enzyme, aspartyl semialdehyde dehydrogenase, ASD, to detect antibacterial activity, led to the isolation of a new pyridoacridine alkaloid, petrosamine B (1). Petrosamine B is a bright blue compound that is sparingly soluble in many organic solvents. The structure of 1 was determined from detailed NMR studies performed in TFA/D2O. Petrosamine B was found to be a weak inhibitor of ASD with an IC50 of 306 μM.

1,2-Bis(1H-indol-3-yl)ethane-1,2-dione (1), a bisindole alkaloid, was isolated from the marine sponge Smenospongia sp. The known compounds indole-3-carbaldehyde (2), 6-bromoindole-3-carbaldehyde (3), and tryptamine (4) and mixtures of the (Z/E) isomers of 6-bromo-2‘-demethylaplysinopsin (5a/5b) and 6-bromo-3‘-deimino-2‘,4‘-bis(demethyl)-3‘-oxoaplysinopsin (6a/6b) were also isolated.

Psammaplin A 11‘-sulfate (3) and bisaprasin 11‘-sulfate (4) have been isolated from the marine sponge Aplysinella rhax, along with the known psammaplin A (1). Their structures were determined on the basis of their spectroscopic data. Compounds 1 and 3 inhibited [³H]1,3-dipropyl-8-cyclopentylxanthine binding to rat-brain adenosine A1 receptors.

Adociasulfate-9 (1) and the known adociasulfate-5 (2) were isolated from an extract of the Great Barrier Reef Sponge Adocia aculeata. Structure elucidation by 1D and 2D NMR spectroscopy revealed that 1 is a novel hexaprenoid hydroquinone.

Sideroxylonal C (3), a new phloroglucinol dimer, was isolated from the flowers of Eucalyptus albens through bioassay-guided fractionation. The structure elucidation was based on 1D and 2D NMR experiments, MS analysis, and comparison with sideroxylonals A (1) and B (2). Sideroxylonal C inhibited human plasminogen activator inhibitor type-1 at 4.7 μM without any significant effect on human tissue plasminogen activator.

Chemical investigation of a Great Barrier Reef ascidian, Aplidium longithorax, has resulted in the isolation of two new cyclofarnesylated quinone-derived compounds, longithorones J (1) and K (2). Longithorone J (1) is the first example of a γ-hydroxy-cyclohexenone in this structure class. Longithorone K (2) is a dihydro analogue of longithorone B.

Chemical investigation of the Australian rainforest plant Doryphora sassafras has resulted in the isolation of a new natural product, 2-methyl-1-(p-methoxybenzyl)-6,7-methylenedioxyisoquinolinium chloride (1). The iodide salt of compound 1 has previously been synthesized but only partially characterized. This paper reports the full spectroscopic characterization of 1 by MS, IR, UV, and NMR data.

Triunia erythrocarpa was identified as containing alkaloids during chemical screening of Queensland Proteaceae using Dragendorff's reagent. A new tropane, 10-hydroxydarlingine (1), and the known tropane, darlingine (2), were isolated from the leaves of T. erythrocarpa. The absolute stereochemistry of 10-hydroxydarlingine (1) was assigned using the advanced Mosher method. T. erythrocarpa is only the seventh member of the Proteaceae to have been shown to produce alkaloids.

Chemical investigation of the Australian ascidian Pseudodistoma aureum has resulted in the isolation of a new β-carboline, eudistomin V (1). The known compounds eudistomin H (2) and I (3) were also isolated, and all compounds had their structures determined by spectroscopic means.

5-Hydroxytryptamine (5-HT) and hypoxanthine were isolated chromatographically from the holothurianPentacter crassa. This study was initiated as a result of the observed hypotensive activity of aP. crassaextract. This activity was also encountered in extracts of the holothuriansThelenota ananusandStichopus chloronatusand can be attributed to 5-HT.

Intravenous administration to rats of the aqueous extract of the soft coralNephtheasp. caused an increase in heart rate and blood pressure. The cardioactive constituent was isolated and shown to be 3-hydroxy-4-methoxyphenethylamine.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The aqueous ethanolic extract of 2 related marine spongesHaliclonasp. andChalinopsillasp. displayed antidermatophyte activities specific forTrichophyton mentagrophytes. The active consituent of both sponges was isolated and shown to be L-azetidine-2-carboxylic acid.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.