Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin

A convergent synthesis of (4R,15R,16R,21S)-rollicosin (1) and (4R,15S,16S,21S)-rollicosin (2) was accomplished. Hydroxy lactone 6a and/or 6b were synthesized from 4-pentyn-1-ol, and α,β-unsaturated lactone 7 was synthesized from γ-lactone 8 and 5-hexen-1-ol. Inhibitory activity of these compounds was examined with bovine heart mitochondrial complex I.     

Isolation, structure elucidation and bioactivity of schischkiniin, a unique indole alkaloid from the seeds of Centaurea schischkinii

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea schischkinii afforded a novel indole alkaloid, named schischkiniin (1), together with four lignans, arctiin (2), matairesinoside (3), matairesinol (4), and arctigenin (5), and three flavonoids, astragalin (6), afzelin (7) and apigenin (8). While the structure of schiskiniin (1) was established unequivocally by UV, HRFABMS and a series of 1D and 2D NMR analyses, all known compounds were readily identified by comparison of their spectroscopic data with literature data. The free radical scavenging properties of these compounds were assessed using the DPPH assay, and their general toxicity and cytotoxicity were evaluated, respectively, by brine shrimp lethality and MTT cytotoxicity assays with CaCo-2 colon cancer cell lines. Arctigenin (5) exhibited promising in vitro anticancer activity (IC₅₀=7 μM) while with schischkiniin (1) the activity was of moderate level (IC₅₀=76 μM).     

Banchromene and other secondary metabolites from the endophytic fungus Fusarium sp. obtained from Piper guineense inhibit the motility of phytopathogenic Plasmopara viticola zoospores

A new chromene, (S)-banchromene (1), together with seven known compounds, ergosterol, beauvericin (2), fusaproliferin (3), radicinin (4), poly(3-hydroxybutyric acid) (PHB, 5), N-methylpyrrolidone and an inseparable mixture of isochromene derivatives 6a, 6b, were isolated from a culture of Fusarium sp. strain CAMKT24b1, an endophytic fungus from the leaves and twigs of Piper guineense (Piperaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic data; the absolute configuration of 1 was determined by ab initio-calculation of the optical rotation. In tests with the zoospores of the grapevine downy mildew pathogen Plasmopara viticola, compounds 1–4 showed moderate to high levels of motility-impairing activity at concentrations as low as 2.5 μg/mL. Compound 2 was the most active, exhibiting both motility-halting and lytic activities. Furthermore, compounds 2 and 3 displayed significant cytotoxic activity against brine shrimp larvae (Artemia salina) at 10 μg/mL. This is the first report on motility inhibitory and lytic activities of metabolites from an endophytic Fusarium species against the zoospores of the downy mildew pathogen P. viticola.     

Lyconadins C and F, new Lycopodium alkaloids from Lycopodium complanatum

New Lycopodium alkaloids, lyconadins C (1) and F (2), were isolated from the club moss Lycopodium complanatum. Lyconadin C (1) is a new C₁₆N₂-type Lycopodium alkaloid possessing unique fused-tetracyclic ring system consisting of a cycloheptene ring fused to a decahydroquinoline and pyridone rings. Lyconadin F (2) possesses a primary amide moiety in its molecular, which is the first example of Lycopodium alkaloids. Biogenetically, lyconadins C (1) and F (2) might be related to lyconadins A (4) and B (5). The structures and relative stereochemistry of 1 and 2 were elucidated on the basis of spectroscopic data. The absolute stereochemistry of 2 was elucidated by chemical correlations with lyconadin B (5) through hemiaminal form of lyconadin F (3).     

Psoracorylifols A-E, five novel compounds with activity against Helicobacter pylori from seeds of Psoralea corylifolia

Five novel compounds, psoracorylifols A-E (1-5) with important activity against Helicobacter pylori have been isolated from a well-known traditional Chinese medicine (TCM), the seeds of Psoralea corylifolia. The structures of compounds 1-5, including their absolute configurations, were established on the basis of spectral methods and biogenetic reason. The structure of 1 was confirmed by a single-crystal X-ray diffraction. Psoracorylifols D and E (4 and 5) represent an unprecedented carbon skeleton. The biogenetic origin of psoracorylifols A-E (1-5) was also postulated.     

Structures and cytotoxicities of fascaplysin and related alkaloids from two marine phyla—Fascaplysinopsis sponges and Didemnum tunicates

The structural variations and bioactivity properties of the alkaloids in the fascaplysin (1) and the reticulatine (3) families were examined. Four organisms were analyzed consisting of two collections of the sponge Fascaplysinopsis reticulata and two collections of the tunicate Didemnum sp. Reported are the isolation of three new compounds: 3-bromofascaplysin (2), 14-bromoreticulatine (4), and 14-bromoreticulatate (6) along with reticulatate (5) previously known as a semi-synthetic product of 1. Compounds 1 and 5 showed selectivity in a cell based cytotoxicity assay.     

Makomotines A to D from Makomotake, Zizania latifolia infected with Ustilago esculenta

Four novel compounds, makomotines A to D (1–4), along with two known ones (5, 6) were isolated from Makomotake, Zizania latifolia infected with Ustilago esculenta. The structures were determined or identified by the interpretation of spectroscopic data. Compound 1 suppressed the formation of osteoclast without toxicity.     

Anti-Pseudomonas aeruginosa xanthones from the resin and green fruits of Cratoxylum cochinchinense

Cochinchinones I-L (1-3 and 13) along with 11 known xanthones (4-12, 14, and 15) were isolated from the resin and green fruits of Cratoxylum cochinchinense. In addition, four new acetylated compounds (16-19) were derivatized from 7-geranyloxy-1,3-dihydroxyxanthone (14) and 3-geranyloxy-1,7-dihydroxyxanthone (15). All compounds were characterized on the basis of spectroscopic analyses. The structures of cochinchinone I (1), a monoacetate (18) and a dibrosylate (20), were also confirmed by X-ray diffraction analysis. The antibacterial and antifungal activities of selected compounds were evaluated as well.     

New cytotoxic sesquiterpenes from the red algae Laurencia obtusa and Laurencia microcladia

Three new sesquiterpenes (1-3), along with five known (5-9), were isolated from the organic extract of the red alga Laurencia obtusa, collected from the coastal rocks of Serifos in the Aegean Sea. A new dimeric sesquiterpene of the cyclolaurane-type (4) along with four previously reported (7, 10-12) metabolites, were isolated from the extract of Laurencia microcladia, collected at Chios island in the North Aegean Sea. The structures and the relative stereochemistry of the compounds are proposed on the basis of their spectral data. The cytotoxicity of the isolated metabolites was evaluated against several cell lines including human tumor cell lines.     

Antimicrobial sesquiterpenes from the Chinese medicinal plant, Chloranthus angustifolius

Two new eudesmane-type sesquiterpenes, 9α-hydroxycurcolonol (1) and 3α-hydroxy-4-deoxy-5-dehydrocurcolonol (2), along with nine known sesquiterpenes (3–11), were isolated from the roots of Chloranthus angustifolius. The antimicrobial activities of compounds 1–11 were evaluated against five bacteria and six fungal strains. Compounds 6–11 showed potent activities against Candida albicans with MIC values ranging from 4 to 8 μg/mL. The structures of the two new compounds 1 and 2 were established by a detailed analysis of their NMR and mass spectroscopic data.     

New pyridoacridine alkaloids from the purple morph of the ascidian Cystodytes dellechiajei

Two new pyridoacridine alkaloids, 13-didemethylaminocycloshermilamine D (1) and demethyldeoxyamphimedine (2), were isolated from the purple chromotype of the Western Mediterranean ascidian Cystodytes dellechiajei. This morph also contained the known shermilamine B (3), kuanoniamine D (4), N-deacetylshermilamine B (5), N-deacetylkuanoniamine D (6), styelsamines C (7), and D (8). The structures of new compounds were elucidated on the basis of spectroscopic data. A hypothetic biosynthetic pathway from the tetracyclic styelsamine D (8) was proposed for both compounds 1 and 2 and their antimicrobial potential was evaluated.     

Two lignans,one alkaloid,and flavanone from the twigs of Feroniella lucida

Four new compounds, two lignans; lucidenal and lucidanin (1 and 2), one alkaloid (3), and one flavanone (4) together with 26 known compounds (5–30), were isolated from the twigs of Feroniella lucida. The structures of the new compounds were determined on the basis of spectroscopic analyses. Lucidenal 1 showed cytotoxicity against HuCCA-1, A549, MOLT-3 and HepG2 cancer cell lines with IC₅₀ values of 4.27, 9.59, 2.31, and 6.50 μg/mL, respectively. A plausible biosynthetic pathway of 1 was proposed.     

Excavatoids A-D, new polyoxygenated briaranes from the octocoral Briareum excavatum

Three polyoxygenated briaranes, including two new compounds, excavatoids A (1) and B (2), and a known metabolite, briaexcavatin I (3), were isolated from the cultured octocoral Briareum excavatum. Moreover, the wild type B. excavatum, collected off southern Taiwan coast, yielded two new 5,6-epoxybriaranes, excavatoids C (4) and D (5). The structures of new compounds 1, 2, 4, and 5 were determined by spectroscopic methods and the structure of 1 was further confirmed by X-ray diffraction data analysis. The X-ray structure for briaexcavatin I (3) was also reported for the first time. Excavatoid A (1) is the first briarane which possesses six hydroxy groups and a 17-methoxy group. Excavatoid C (4) is the first 12,13-secobriarane which possesses a novel pentacyclic skeleton with an ?-lactone. Excavatoid D (5) displayed moderate inhibitory effects on superoxide anion generation and elastase release by human neutrophils.     

Five novel norcembranoids from Sinularia leptoclados and S. parva

Three new norcembrane-based diterpenoids, leptocladolides A (1), B (4) and C (5), along with five known metabolites 6-10, have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados. Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1-epi-leptocladolide A (2) and 7E-leptocladolide A (3), in addition to 1 and 7. The structures of new metabolites 1-5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.     

New briaranes from the octocorals Briareum excavatum (Briareidae) and Junceella fragilis (Ellisellidae)

Six 12-hydroxybriaranes, including four new diterpenoids, briaexcavatins I-L (1-4), and two known metabolites, excavatolides C (5) and E (6), have been isolated from the cultured scleraxonia Briareum excavatum. In addition, the gorgonian coral Junceella fragilis yielded a new chlorinated briarane, fragilide C (10). The structures of above compounds were determined by spectroscopic methods and the structures of 5 and 6 were further confirmed by X-ray data analysis for the first time. The absolute configuration of 6 was elucidated by chemical conversion. Some of these briaranes have displayed inhibitory effects on superoxide anion generation by human neutrophils.     

Stereochemical challenges in characterizing nitrogenous spiro-axane sesquiterpenes from the Indo-Pacific sponges Amorphinopsis and Axinyssa

An investigation was conducted to identify the structures and bioactive properties of five compounds isolated from the Halichondrida sponges Amorphinopsis foetida and Axinyssa aplysinoides. All compounds possessed the spiro-axane sesquiterpene core and all were substituted at C-2 with nitrogen containing functionality. The stereochemistry of one known compound has been revised to (2R,5R,10S)-2-formamido-6-axene (3). It exhibited mild selective solid tumor and mild antibacterial activity and was found from Axinyssa. A second known substance whose stereochemistry has also been revised, (2R,5R,10S)-2-isothiocyanato-6-axene (4) plus its undescribed diastereomer (5) were isolated from Amorphinopsis. Both sponges were the source of two new N-phenethyl-2-formamido-6-axene diastereomeric compounds 6 and 7. No solid tumor or antibacterial activity was found for 4-7.     

Trypanocidal constituents of Dracocephalum komarovi

Trypanocidal constituents of Dracocephalum komarovi were investigated. Under guidance of the in vitro trypanocidal activity against epimastigotes of Trypanosoma cruzi, the causative agent of Chagas' disease, two new diterpenes, dracocequinones A (1) and B (2), and two known triterpene acids, ursonic acid and ursolic acid, were isolated as trypanocidal constituents, in addition to previously reported diterpenes, cyclocoulterone (4), komaroviquinone (5), dracocephalone A (6) and komarovispirone (7). Furthermore a new diterpene, komarovinone A (3), was isolated, together with four known terpenes. Among these compounds, komaroviquinone (5) showed the most potent activity with minimum lethal concentration of 0.4 μM. Structure elucidation of the new diterpenes 1-3 was described.     

Novel polyisoprenylated benzophenone derivatives from Garcinia paucinervis

Four novel polyisoprenylated benzophenone derivatives, paucinones A-D (1-4), were isolated from the leaves of the plant Garcinia paucinervis. Paucinones A-C (1-3) contained an unexpected cyclohexane-spiro-tetrahydrofuran moiety. A 1-methylene-3,3-dimethylcyclohexane group never reported before was found in the structure of paucinone D (4). The structures of these compounds were elucidated with spectroscopic evidences. The relative stereochemistries of 1-4 were determined by NOESY correlations. These compounds showed significant cytotoxicities against HeLa cells.     

Lacitemzine, a novel sesquiterpene acid from the Tunisian plant Pulicaria laciniata (Coss. et Kral.) Thell.

The flowers of Pulicaria laciniata (Coss. et Kral.) Thell. (Asteraceae) afforded a new sesquiterpene acid 1, named lacitemzine together with the three known compounds, 4-hydroxy-3-methoxypyridine 2, β-sitosterol-3-O-β-d-glucoside 3 and 1,3,5-trimethoxybenzene 4. The structure of compound 1, 2-(2,6-dimethyl-3,4,5,6,7,8,9,10-octahydro-5,8-oxaazulen-9-yl)acrylic acid, contains a guaiane skeleton and was elucidated by spectroscopic procedures including 2D-NMR and X-ray diffraction.     

Cytotoxic and novel skeleton compounds from the heartwood of Chamaecyparis obtusa var. formosana

The novel skeleton compounds, chamaecypanone C (3) and obtunorlignan A (4) were isolated from the heartwood of Chamaecyparis obtusa var. formosana. The structure of 3 was elucidated as a dimeric of monoterpene and norlignan with tricyclo[5.2.2.0^2.6]undecane and the structure of 4 was elucidated as a norlignan skeleton by spectroscopic methods. Compound 3 exhibits potent cytotoxic activity against several human cancer cells with IC₅₀ values ranging from 0.19 to 0.52 μM, whereas 4 has no activity.