A pair of unprecedented cyclohexylethanoid enantiomers containing unusual trioxabicyclo[4.2.1]nonane ring from Clerodendrum bungei

A pair of unprecedented enantiomers (1a/1b) of cyclohexylethanoid bearing an unusual trioxabicyclo[4.2.1]nonane ring, along with two known structurally related cyclohexylethanoids, (+)-rengyolone (2) and cleroindicin E (3), were isolated from the aerial parts of Clerodendrum bungei. The structures and absolute configurations of the enantiomers were determined by comprehensive spectroscopic analysis, single-crystal X-ray diffraction, and quantum mechanical calculation of the electronic circular dichroic (ECD) spectra. The postulated biogenetic pathway of 1a/1b was also discussed.     

Novel sesquiterpenoids from the Formosan soft coral Paralemnalia thyrsoides

Three sesquiterpenoids with unprecedented skeletons, paralemnanone (1), isoparalemnanone (2), and paralemnanol (3), were isolated from the Formosan soft coral Paralemnalia thyrsoides. Their structures were elucidated by extensive spectroscopic analysis, and the structure of 1 was further confirmed by X-ray crystallographic analysis. The absolute stereochemistries of 1-3 were established by application of the Mosher’s method on 2.     

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.     

Dolastanes from the brown alga Dilophus spiralis: absolute stereochemistry and evaluation of cytotoxicity

Five new dolastanes (1-5) were isolated from the brown alga Dilophus spiralis. The structural elucidation of the isolated compounds and the assignment of relative stereochemistry were based on analyses of their spectroscopic data. The structure proposed for 1 was confirmed by single crystal X-ray diffraction analysis, whereas its absolute stereochemistry was determined using the modified Mosher's method. The cytotoxicity of 1-4 was evaluated against seven cell lines.     

Leccinine A, an endoplasmic reticulum stress-suppressive compound from the edible mushroom Leccinum extremiorientale

Leccinine A (1) along with a known compound (2), were isolated from the edible mushroom Leccinum extremiorientale. The structure of 1 was determined by the interpretation of spectral data. Leccinine A showed protective activity against endoplasmic reticulum stress-dependent cell death. Seven analogues (3-9) of 1 were synthesized in order to evaluate the structure-activity relationship, and the result indicated that the formamide group of 1 was indispensable for the activity.     

Isolation and synthesis of N-acyladenine and adenosine alkaloids from a southern Australian marine sponge, Phoriospongia sp.

Chemical fractionation of the southern Australian marine sponge Phoriospongia sp. (CMB-03107) yielded phorioadenine A (1) as a nematocidal agent and the first reported example of a 6-N-acyladenine natural product. The structure of 1 was confirmed by spectroscopic analysis and the chemical synthesis of racemic (1a) and enantiomeric (1b) analogues. HPLC–ESIMS analysis of the crude sponge extract with comparisons to the synthetic 6-N-acyladenosine 2a provided evidence that the biosynthetically related adenosine, phorioadenosine A (2), was present as a trace co-metabolite. The rare starfish metabolite asterubine (3) was also isolated as a co-metabolite, and its structure confirmed by spectroscopic analysis and chemical synthesis. Biological investigations confirmed that natural products 1–3 and synthetic analogues 1a–e and 2a were not cytotoxic to multiple mammalian cancer cell lines, or Gram-positive or -negative bacteria. Nematocidal activity (inhibition of larval development of Haemonchus contortus) detected in the Phoriospongia sp. extract was attributed to 1 (LD₉₉ 31 μg/mL), with preliminary structure–activity relationship investigations confirming the importance of the N-acyl side chain.     

Infectopyrone, a potential mycotoxin from Alternaria infectoria

A new metabolite, infectopyrone (1), has been isolated from the filamentous fungus Alternaria infectoria. The structure of 1 was elucidated by analysis of 2D NMR spectroscopic data. Compound 1 is an α-pyrone resembling known toxins, and is a useful phenotaxonomic marker for the A. infectoria species-group. Infectopyrone (1) was also produced by species within Stemphyllium and Ulocladium, and found in mouldy food.     

Novel alkaloids, paxdaphnines A and B with unprecedented skeletons from the seeds of Daphniphyllum paxianum

Two novel Daphniphyllum alkaloids with unprecedented skeletons, namely paxdaphnines A (1) and B (2), have been isolated from the seeds of Daphniphyllum paxianum. Paxdaphnine A (1) is a 19-nor-Daphniphyllum alkaloid with highly caged skeleton, and paxdaphnine B (2) is the first 1,19-bisnor-Daphniphyllum alkaloid. The relative structures of 1 and 2 were elucidated by spectral methods, and their unique biosynthetic pathway postulated. The absolute structure of 1 was determined by X-ray diffraction of the iodide derivative (1a) of 1, and the absolute stereochemistry of 2 was proposed by correlation with the biosynthetic pathway for 1.     

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.     

New microviridins from a water bloom of the cyanobacterium Microcystis aeruginosa

Three new microviridins namely, SD1684 (1), SD1634 (2), and SD1652 (3), were isolated from the hydrophilic extract of Microcystis aeruginosa. The planar structures of compounds 1-3 were determined by homonuclear and inverse-heteronuclear 2D-NMR techniques as well as by high-resolution mass spectrometry. The absolute configuration of the asymmetric centers was studied using Marfey's method for HPLC. Compounds 1-3 contain l-threo-β-hydroxy aspartic acid as a building block of the peptide chain. This is the first example where microviridins contain non-proteinogenic amino acid in their structure. Compound 2 is a mild serine protease inhibitor.     

Rumphellatin A, the first chloride-containing caryophyllane-type norsesquiterpenoid from Rumphella antipathies

A novel chloride-containing 14C norsesquiterpenoid, rumphellatin A (1), was isolated from the Formosan gorgonian coral Rumphella antipathies. The structure of metabolite 1 was determined on the basis of spectral data analysis and the configuration of 1 was further supported by molecular mechanics calculations. Rumphellatin A (1) showed activity against Gram-negative bacteria.     

Polyhydroxy pregnanes from Dregea volubilis

Three new polyhydroxy pregnanes named dregealol (1), volubilogenone (2) and volubilol (3) were isolated from the flowers of Dregea volubilis, and their structures elucidated from extensive 2D NMR analysis. The structure of volubilol (3) was confirmed by X-ray crystallographic studies. The known pregnane derivatives drevogenin D, iso-drevogenin P and 17α-marsdenin were also isolated.     

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.     

Shimalactone A, a novel polyketide, from marine-derived fungus Emericella variecolor GF10

Shimalactone A (1), a novel polyketide having bicyclo[4.2.0]octadiene and oxabicyclo[2.2.1]heptane units, was isolated from a cultured marine fungus of Emericella variecolor GF10. The stereo structure of 1 was deduced from 2D NMR and X-ray crystallographic analyses of 1 and its derivatives. The absolute structure of 1 was determined by application of the CD allylic benzoate rule to the benzoate derivative of 1. Shimalactone A (1) induced neuritogenesis at 10 μg/mL against neuroblastoma Neuro 2A cells.     

Oryzamutaic acids H-J, new alkaloids from an Oryza sativa mutant with yellow endosperm

Three new nitrogen-containing heterocyclic alkaloids, oryzamutaic acids H-J (1-3), were isolated from the endosperm (polished rice) of an Oryza sativa mutant. The structures and relative stereochemistries of 1-3 were elucidated on the basis of spectroscopic analyses. The presence of three carbons, each bound to a carboxyl group and a nitrogen atom in the structure of 1, suggests that oryzamutaic acids H-J (1-3) are generated from three molecules of a single amino acid.     

Polyketides produced by Daldinia loculata cultured from Northern Manitoba

The fungus present in a soil sample collected from Northern Manitoba was cultured. The natural products produced by this organism were isolated and identified as the polyketides (1), (2), (3). A trace amount of the aromatic alcohol tyrosol (4) was also isolated. This organism was identified as Daldinia loculata by sequencing of the internally transcribed spacer region of the nuclear ribosomal DNA. The polyketides 1-3 were assayed against E. coli and it was observed that 1 displayed mild antibiotic activity.     

An unusual indole alkaloid with anti-adenovirus and anti-HSV activities from Alstonia scholaris

A novel alkaloid, 17-nor-excelsinidine (1), possessing an unusual 1-azoniatricyclo [4.3.3.0] undecane moiety was isolated from the twigs and leaves of Alstonia scholaris alongside its biogenetically related strictamine (2). The structure and absolute stereochemistry of compound 1 were rigorously determined by a combination of NMR spectroscopy and X-ray crystallography. The 17-nor-excelsinidine (1) and strictamine (2) showed significant inhibitory activity against herpes simplex virus (HSV) and adenovirus (ADV).     

Mekongenines A and B, two new alkaloids from Bousigonia mekongensis

Mekongenine A (1) possessing an unprecedented structure constituted from the union of a rare 2,7-seco eburnamine half and an aspidospermine alkaloid, together with a new bisindole alkaloid, mekongenine B (2), consisting of an eburnamine-aspidospermine type skeleton, was isolated from Bousigonia mekongensis. Their structures were elucidated by means of spectroscopic methods and those of 2 were further confirmed by X-ray diffraction. The absolute configurations of 1 and 2 were determined by comparison of quantum chemical TDDFT calculated and experimental ECD spectra. Mekongenines A (1) and B (2) exhibited cell growth inhibitory activities against various human cancer cell lines.     

Five new eremophilane derivatives from Ligularia sagitta

Ligulasagitins A-E (1-5), five new eremophilane-derived metabolites possibly formed via a Diels-Alder reaction in the biosynthetic process, were isolated from Ligularia sagitta Maxim. Among them 1 and 2 possess a novel C19 skeleton, 4 and 5 are two novel dimeric eremophilane type derivatives. Their structures were determined by extensive spectroscopic analysis and the structure of 2 was also confirmed by a single-crystal X-ray diffraction analysis. Furthermore, 4 and 5 showed weak cytotoxic activity against HL-60 (human promyelocytic leukemia) cells.     

Cytotoxic bromoditerpenes from the red alga Sphaerococcus coronopifolius

Three new brominated diterpenes (1, 2, 8), along with six previously reported metabolites (3-7, 9), were isolated from the organic extract of Sphaerococcus coronopifolius, collected in Palaiokastritsa bay at the west coasts of Corfu Island. The structures of the new natural products, as well as their relative stereochemistry, were established by means of spectral data analyses, including 2D experiments. The absolute stereochemistry of 2 and 4 as well as the structure revision of the previously reported metabolite 3 were established by X-ray crystallographic analyses. The cytotoxicity of the isolated metabolites was evaluated against the NSCLC-N6-L16 and A549 human lung cancer cell lines.