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A unique set of thiomethylated canthin-6-one derivatives was isolated from Boletus curtisii. The bright yellow color of this mushroom is caused by two optically active canthin-6-one sulfoxides for which the names curtisin and 9-deoxycurtisin are proposed. The structures of the new compounds were established by MS and NMR methods and the absolute configuration of the sulfoxides determined by quantum chemical calculations. This is the first occurrence of canthin-6-one alkaloids outside of higher plants. The chemotaxonomic implications of these findings are discussed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

The chiroptical properties of calliactine (2) have been studied experimentally as well as by quantum chemical calculations based on density functional theory (DFT). According to the DFT calculations, the four energetically lowest conformers of the title compound lie within a range of 1.1 kcal/mol and are separated from other conformers by an energy gap of nearly 9 kcal/mol. Based on their geometries, the excitation energies and rotational strengths have been calculated using time-dependent DFT (TDDFT) and the dipole velocity formalism. The circular dichroism (CD) spectrum of calliactine has been obtained as a Boltzmann-weighted superposition of the spectra of each of the four structures. By comparison of the calculated and experimental CD spectra, the absolute configuration of calliactine has been elucidated as S. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004

The marine alkaloid ascididemin (ASC) was shown to exert cytotoxicity even against multidrug-resistant cancer cells. Here, we address the signaling pathways utilized by ASC to trigger apoptosis in Jurkat leukemia T cells. We show that ASC (0.5-20 microM) induces a mitochondrial pathway that requires the activation of the initiator caspase-2 upstream of mitochondria. ASC-triggered apoptosis occurred independent of CD95, but required mitochondrial dysfunction. The activation of caspase-2 was shown to precede the processing of caspase-8, -9 and -3. The specific caspase-2 inhibitor zVDVADfmk abrogated ASC-induced DNA fragmentation almost completely. Overexpression of Bcl-x(L) blocked caspase-8 but not caspase-2 processing. Conversely, caspase-2 inhibition strongly reduced caspase-9 activation. As a possible link between caspase-2 and mitochondrial dysfunction, Bid was found to be cleaved by ASC. In addition, JNK was activated by ASC upstream of mitochondria via reactive oxygen species. The specific JNK inhibitor SP600125 partially inhibited caspase-2 and -9 processing as well as cytochrome c release and DNA fragmentation indicating that JNK contributes to, but is not necessary for ASC-mediated apoptosis. Thus, ASC triggers a pathway in which early activation of caspase-2 provides a possible link between its DNA-damaging activity and the induction of mitochondrial dysfunction. The activation of JNK contributes to this signaling upstream of mitochondria.

Three new disulfides, pentaporins A, B and C, with anthelmintic in vitro activity have been isolated from the mediterranean bryozoan Pentapora fascialis. The structures of these compounds were determined by 1D and 2D NMR spectroscopy, mass spectrometry and EDX-analysis. The pentaporins show activity against Trichinella spiralis.

The tunic of Cystodytes dellechiajei (Poly- citoridae), a colony-forming species of the Ascidiacea that contains biologically active alkaloids, was investigated using light microscopy, laser-scanning microscopy and nuclear magnetic resonance techniques. The colonies contain numerous individual zooids, which are embedded in a common tunic. Each zooid is protected by a firm capsule of overlapping calcareous spicules. The colonies lack blood vessels in the tunic, but six morphologically different types of tunic cells were found: pigment cells, bladder cells, vacuolated filopodial cells, granular filopodial cells, morula cells and granular cells. Rod-like bacteria were found in the tunic matrix. Bladder cells and pigment cells could be identified as storage units for acid and pyridoacridine alkaloids, making the tunic inedible and repelling predators. Filopodial cells have long filopodia, which probably are connected to each other. They may be involved in transportation processes within the tunic tissue. The functions of the morula cells and the granular cells are unknown as yet. With its several specialised cells, the tunic of C. dellechiajei represents a dynamic living tissue containing biologically active compounds.

The new antifungal strobilurins I (1) and K (19) are 3,4-dihydro-2H-benzo[b][1,4]dioxepin derivatives. Their structure and stereochemistry was determined by degradation to aldehyde 3. Both enantiomers of 3 were synthesised and the absolute configurations assigned by the high-field 1H NMR variant of Mosher's method. (S)- 3 is identical with the compound derived from the natural products. In the course of these investigations the epoxide structures 15, 16 and 17 previously assigned to strobilurin D, hydroxystrobilurin D and 9-methoxystrobilurin K have to be changed in 18, 21 and 20, respectively. All these compounds possess the same benzodioxepin core structure and (S)-configuration as strobilurin I (1).

The polyenoyltetramic acid physarorubinic acid (2) has been isolated from microplasmodia of the slime mold Physarum polycephalum. The structure was elucidated by means of 1D- and 2D-NMR, IR, and UV spectroscopy and mass spectrometry. The stereochemistry was proven by synthesis of the tetramic acid unit and application of circular dichroism. It was shown that plasmodia of a white mutant strain also contain yellow pigments.

The ascidian Dendrodoa grossularia , collected in the Baltic Sea, contains the new 1,3,5-oxadiazin-2-one alkaloid alboinon ( 1 ).

An orange pigment named echinotinctone was isolated from the wood-rotting polypores Echinodontium tinctorium and Pyrofomes albomarginatus. Its structure was elucidated as2, 6-dihydroxy-1, 8-dimethyl-3H-xanthen-3-one (1) on the basis of spectroscopic and chemical studies.1 represents the first naturally occurring pigment with a simple fluorone chromophore. Echinotinctone (1) constitutes the first simple fluorone pigment from fungi. Download : Download full-size image

The structures of two quinone methide pigments from fruiting bodies of Russula flavida have been elucidated. Russulaflavidin and its dihydro derivative contain the same chromophore as pristimerin and represent the first triterpenoids with a shionane (D:A friedo-18, 19-secolupane) skeleton isolated from fungi.

Novel Diterpenoids from the Toadstools Tricholoma aurantium and T. fracticum (Agaricales)1 Two novel diterpenoids trichaurantin (1) and its 6-O-acetyl derivative 2 have been isolated from Tricholoma species. Their structures were established by spectroscopic methods and an X-ray crystal analysis, 1 and 2 appear to be biosynthetically related to the neodolabellane and dolastane group of diterpenes and can be designated as 2,3-seconeodolastane derivatives.

The biosynthesis of shermilamine B is proposed which involves tryptophan, dopamine and cysteine.

The tunicate Clavelina lepadiformis, which was collected in the North Sea, contains the new decahydroquinoline alkaloid lepadin A (1), in addition to the pentachlorooctatriene 2. The structures have been determined on the basis of spectroscopic evidence and in comparison with published data for compound 2.

The ascidian Dendrodoa grossularia , collected in the Baltic Sea, contains the new 1,3,5-oxadiazin-2-one alkaloid alboinon ( 1 ).

The polyenoyltetramic acid physarorubinic acid (2) has been isolated from microplasmodia of the slime mold Physarum polycephalum. The structure was elucidated by means of 1D- and 2D-NMR, IR, and UV spectroscopy and mass spectrometry. The stereochemistry was proven by synthesis of the tetramic acid unit and application of circular dichroism. It was shown that plasmodia of a white mutant strain also contain yellow pigments.

Illumination results in increased formation of metabolites 1 and 2 in the plasmodia of the slime mold Physarum polycephalum. This was determined from HPLC studies undertaken in the search for the photoactive substances involved in the "blue-light phenomenon". The isolation and structure elucidation of 1 and 2 is described.

A yellow optically-active pigment, chrysophysarin A ( 1 ), has been isolated from microplasmodia of the slime mould Physarum polycephalum . The structure was established by means of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration was assigned by the synthesis of N -(3,3-dimethylacryloyl) derivatives of ( S )- and ( R )-leucine and by comparison of the corresponding CD spectra. The biosynthesis of the compound was elucidated by feeding labeled acetate to the plasmodia.

A yellow optically-active pigment, chrysophysarin A ( 1 ), has been isolated from microplasmodia of the slime mould Physarum polycephalum . The structure was established by means of 1D and 2D NMR spectroscopy and mass spectrometry. The absolute configuration was assigned by the synthesis of N -(3,3-dimethylacryloyl) derivatives of ( S )- and ( R )-leucine and by comparison of the corresponding CD spectra. The biosynthesis of the compound was elucidated by feeding labeled acetate to the plasmodia.

The tunicate Clavelina lepadiformis, which was collected in the North Sea, contains the new decahydroquinoline alkaloid lepadin A (1), in addition to the pentachlorooctatriene 2. The structures have been determined on the basis of spectroscopic evidence and in comparison with published data for compound 2.

Mushrooms of the genus Retiboletus contain the retipolides A–D (1, 6–8), unusual 14-membered spiromacrolides with a biphenyl ether linkage. The structures of these metabolites suggested a biogenetic sequence starting from retipolide E (16), which could furnish the unique 2(3H)-oxepinone unit of retipolide C (7) via an oxidative enlargement of the 4-hydroxyphenyl ring. A subsequent O/C-acyl shift would then lead to the cyclopenta[c]pyran system of retipolide A (1). The proposed precursor 16 was synthesized and subsequently detected in the fungal extract in addition to the probable biosynthetic intermediates butyrolactone II (13), tyrosol (14), and secoretipolide E (15). The structural elucidation of retipolide A (1) was accomplished after transformation into a methoxyfulvene derivative 2a, and the absolute (R) configuration of 1 was assigned by a single-crystal X-ray analysis of the corresponding (S)-sec-butoxyfulvene analogue 2b. Some samples of R. retipes/ornatipes contained isoretipolide A (9), an isomer of 1 with a highly strained 12-membered lactone ring incorporating two C,C-coupled 4-hydroxyphenyl units. A comparison of the CD spectrum of retipolide A (1) with those of the other retipolides and isoretipolide A (9) indicates that all of these macrolides possess R configuration. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Lascivol, the Bitter Component of Tricholoma lascivum (Agaricales) The structure of lascivol (1), the bitter principle of the toadstool Tricholoma lascivum, has been elucidated by chemical and spectroscopic studies including a single crystal X-ray structure analysis. 1 is degraded to dimethyl L-glutamate (6) and 5-methoxy-2,4-dimethylindole (5) by acid methanolysis.

The structure of fulvoferruginin (1), a carotane derivative from cultures of Marasmius fulvoferrugineus, has been established by spectroscopic investigations and an X -ray structure analysis. 1 exhibits antibacterial, antifungal. and cytotoxic activities.

Mushrooms of the genus Retiboletus contain the retipolides A–D (1, 6–8), unusual 14-membered spiromacrolides with a biphenyl ether linkage. The structures of these metabolites suggested a biogenetic sequence starting from retipolide E (16), which could furnish the unique 2(3H)-oxepinone unit of retipolide C (7) via an oxidative enlargement of the 4-hydroxyphenyl ring. A subsequent O/C-acyl shift would then lead to the cyclopenta[c]pyran system of retipolide A (1). The proposed precursor 16 was synthesized and subsequently detected in the fungal extract in addition to the probable biosynthetic intermediates butyrolactone II (13), tyrosol (14), and secoretipolide E (15). The structural elucidation of retipolide A (1) was accomplished after transformation into a methoxyfulvene derivative 2a, and the absolute (R) configuration of 1 was assigned by a single-crystal X-ray analysis of the corresponding (S)-sec-butoxyfulvene analogue 2b. Some samples of R. retipes/ornatipes contained isoretipolide A (9), an isomer of 1 with a highly strained 12-membered lactone ring incorporating two C,C-coupled 4-hydroxyphenyl units. A comparison of the CD spectrum of retipolide A (1) with those of the other retipolides and isoretipolide A (9) indicates that all of these macrolides possess R configuration. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

In the structural elucidation of natural products, problems may arise owing to extensive signal overlap and line broadening in the NMR spectra as well as unexpected chemical reactions. This is illustrated in the analysis of some novel compounds isolated from fruit bodies of toadstools and slime moulds, including infractopicrin, lascivol, retipolide A, arcyroxepin A and rubroflavin. In some cases, the problems could be solved by spectroscopic techniques such as two-dimensional INADEQUATE experiments, nuclear Overhauser enhancement measurements or X-ray structural analysis; in other cases, chemical transformations were necessary to resolve the structure.

Illumination results in increased formation of metabolites 1 and 2 in the plasmodia of the slime mold Physarum polycephalum. This was determined from HPLC studies undertaken in the search for the photoactive substances involved in the "blue-light phenomenon". The isolation and structure elucidation of 1 and 2 is described.

Lipid peroxidation may be initiated either by lipoxygenases or by reactive oxygen species (ROS). Enzymatic oxidation of alpha-linolenate can result in the biosynthesis of cyclic oxylipins of the jasmonate type while free-radical-catalyzed oxidation of alpha-linolenate may yield several classes of cyclic oxylipins termed phytoprostanes in vivo. Previously, we have shown that one of these classes, the E1-phytoprostanes (PPE1), occurs ubiquitously in plants. In this work, it is shown that PPE1 are converted to novel cyclopentenone A1- and B1-phytoprostanes (PPA1 and PPB1) in planta. Enhanced formation of PPE1, PPA1, and PPB1 is observed after peroxide stress in tobacco cell cultures as well as after infection of tomato plants with a necrotrophic fungus, Botrytis cinerea. PPA1 and PPB1 display powerful biologic activities including activation of mitogen-activated protein kinase (MAPK) and induction of glutathione-S-transferase (GST), defense genes, and phytoalexins. Data collected so far infer that enhanced phytoprostane formation is a general consequence of oxidative stress in plants. We propose that phytoprostanes are components of an oxidant-injury-sensing, archaic signaling system that serves to induce several plant defense mechanisms.

The absolute configuration of polycephalin C ( 1 ) isolated from plasmodia of the slime mold Physarum polycephalum is supposed to be 3″R,4″R as found by comparison of CD spectra of the natural product polycephalin C (1) and CD spectra of synthetic bis-benzoates (−)-4 and (+)-4 . An X-ray structure of the corresponding bis-camphanate (+)-3 shows that the exciton chirality method may not be applied on these 1,4-diols in the usual manner.

Prostaglandin E1 is currently marketed as a freeze-dried injectable inclusion complex with alpha-cyclodextrin for the treatment of peripheral arterial diseases. alpha-Cyclodextrin is used as a stabilizing agent and to improve the dissolution characteristics of prostaglandin E1. Upon dilution with the infusion medium, the inclusion complex dissociates almost completely as shown by NMR chemical shift measurements of the complexed and uncomplexed prostaglandin E1. Nuclear Overhauser effect (NOE) measurements of the interacting atoms of alpha-cyclodextrin and prostaglandin E1 provide insight into the structure of the complex.

It covers all classes of natural products: -amino acids -peptides and proteins -carbohydrates -antibiotics -alkaloids -steroids -terpenoids -porphyrins -vitamins -aroma/flavour compounds -chinons -pigments -lipids -toxins -medicinal herbs -substances of moss and ferns -fungi -marine organism -lichen substances -plant protection products and other unusual natural product

Xylaral, a Hydroxyphthalide Derivative from Fruiting Bodies of Xylaria polymorpha (Ascomycetes) Fruiting bodies of Dead Man's Fingers, Xylaria polymorpha, contain a hydroxyphthalide derivative, xylaral (1), which exhibits a violet colour reaction with aqueous ammonia. 1 is a homologue of cyclopaldic acid (5) with a C14-side chain containing an enone moiety.

Illumination results in increased formation of metabolites 1 and 2 in the plasmodia of the slime mold Physarum polycephalum. This was determined from HPLC studies undertaken in the search for the photoactive substances involved in the "blue-light phenomenon". The isolation and structure elucidation of 1 and 2 is described.

The structures of six new drimance sesquiterpenoids, mniopetals A-F, were elucidated by a combination of chemical and spectroscopic methods. The mniopetals are inhibitors of RNA-directed DNA-polymerases.

From roots of Homalomena aromatica three new sesquiterpene alcohols, 1 beta, 4 beta, 7 alpha-trihydroxyeudesmane, homalomenol A, and homalomenol B were isolated together with oplopanone, oplodiol and bullatantriol. The structures of the new constituents were elucidated by spectroscopic investigations and chemical transformations.

Three new inhibitors of cholesterol biosynthesis have been isolated from cultures of Xerula melanotricha and their structures elucidated by spectroscopic methods. Dihydroxerulin (1) in admixture with xerulin (2) strongly inhibits the incorporation of 14C- acetate into cholesterol in HeLa cells while the incorporation of 14C-mevalonate is not affected. Xerulinic acid (3) shows similar biological activities but a higher cytotoxicity.

Asperfuran is a novel antifungal dihydrobenzofuran derivative produced by a strain of Aspergillus oryzae. Asperfuran weakly inhibited chitin synthase from Coprinus cinereus. This inhibition could be abolished by the addition of egg lecithin. In the agar diffusion assay asperfuran induced morphological changes in Mucor miehei at very low concentrations (20 ng/disc) while growth was only partly inhibited. In HeLa S3 and L1210 cells it showed weak cytotoxicity, the IC50 was 25 micrograms/ml.

Strobilurin E is a novel antibiotic of the (E)-beta-methoxyacrylate (MOA) class produced by mycelial cultures of the agaric Crepidotus fulvotomentosus. In addition to an inhibition of fungal respiration, a feature of all MOA-antibiotics, the compound exhibits very high cytostatic activities which are accompanied by reversible morphological alterations of the cells.