Melanocrocin, a polyene pigment from Melanogaster broomeianus (Basidiomycetes).

A new polyene pigment, melanocrocin, has been isolated either from fruit bodies or mycelial cultures of the subterranean fungus Melanogaster broomeianus. The structure of the pigment was determined by spectroscopic methods and chemical transformations. Melanocrocin is the N-acyl derivative of L-phenylalanine methyl ester with a polyolefinic carboxylic acid.

Biosynthesis of 2-aminobenzaldehyde in flowers of Robinia pseudoacacia and Philadelphus coronarius.

Feeding experiments with 13C- and fluorine-labelled precursors were performed to reveal the biosynthesis of 2-aminobenzaldehyde in flowers of Robinia pseudoacacia and Philadelphus coronarius. The results are in agreement with the transformation of anthranilic acid to indole followed by oxidative ring opening and hydrolysis of the resulting N-formyl-2-aminobenzaldehyde. This route differs from that observed in Hebeloma sacchariolens (Basidiomycetes) in which anthranilic acid is directly reduced to 2-aminobenzaldehyde.

Studies on the biosynthesis of 2-hydroxy-1,4-benzoxazin-3-one (HBOA) from 3-hydroxyindolin-2-one in Zea mays.

The ring expansion of 3-hydroxyindolin-2-one to 2-hydroxy-1,4-benzoxazin-3-one (HBOA) was investigated by labelling experiments. Action of the cytochrome P450 enzyme BX4 from maize on 3-hydroxyindolin-2-one under an 18O2 atmosphere induced production of 2-hydroxy-1,4-benzoxazin-3-one in which the ring oxygen--but not the 2-hydroxy group of HBOA--is labelled. A mechanism for this transformation is proposed.

Malassezin--A novel agonist of the arylhydrocarbon receptor from the yeast Malassezia furfur.

The yeast Malassezia furfur converts tryptophan into several indole compounds. One of these, malassezin, was identified as 2-(1H-indol-3-ylmethyl)-1H-indole-3-carbaldehyde (1). It was synthesized from N-Boc-indole-3-carbaldehyde in five steps with 12% overall yield. The compound easily cyclizes to indolo[3,2-b]carbazole (7) which is known to interact with the arylhydrocarbon receptor (AHR). Similarly, malassezin was found to induce cytochrome P450 as an agonist of AHR (EC50 = 1.57 microM) in rat hepatocytes.

Static and phasic cross-talk effects in discrete bimanual reversal movements.

The authors examined the hypothesis that the phasic and the static cross-talk effects found in bimanual movements with different target amplitudes originate at different functional levels of motor control, which implies that the effects can be dissociated experimentally. When the difference between the short and the long amplitudes assigned to the 2 hands of 12 participants was decreased, the static effect disappeared, In contrast, the phasic effect, which can be observed only at short preparation intervals, did not disappear; although it became smaller in absolute terms, in relative terms it did not. In addition, the authors compared the time course of amplitude variability and examined the correlation between left hand and right hand amplitudes. The disappearance of the phasic amplitude assimilation at increasing preparation intervals turned out to be delayed relative to the decline of the correlation between amplitudes. That finding suggests that the assimilation of mean amplitudes and the correlation between left hand and right hand amplitudes are not fully equivalent indicators of intermanual interactions, but may indicate different kinds of inter-limb coupling.

Metabolites of 2-aminophenol from fruit bodies of Lepiota americana (Agaricales).

From the acetone extract of the North American toadstool Lepiota americana 2-aminophenoxazin-3-one (1) and a novel amino-1,4-benzoquinone derivative, lepiotaquinone (2), were isolated. The structure of 2 was confirmed by its preparation from 2-aminophenol and amino-1,4-benzoquinone.

Alkaloids from marine organisms, Part 5. Biomimetic total synthesis of lamellarin L by coupling of two different arylpyruvic acid units.

Reaction of the ethyl 3-arylpyruvate 5a with the methyl 2-bromo-3-arylpyruvate 6b in the presence of the 2-arylethylamine 4 afforded the pyrrole derivative 10, which could be transformed into lamellarin L (1) in five steps. The synthesis proceeds with 38% overall yield and mimics the probable biosynthesis of these marine alkaloids.

Montadial A, a cytotoxic metabolite from Bondarzewia montana.

A new meroterpenoid, montadial A (1), has been isolated from the polypore Bondarzewia montana. Its structure was elucidated by spectroscopic techniques. Montadial A exhibits cytotoxic effects and develops a striking yellow color when treated with KOH.

Synthesis of 1-(2-aminophenyl)isoquinolines and the biological activity of their cis-dichloro platinum(II) complexes.

The broad biological effects of isoquinolines prompted us to use them as chelating, nonleaving ligands in cis-platinum(II) antitumor complexes. The synthesis of several 1-(2-aminophenyl)isoquinoline derivatives with different levels of hydrogenation and varying substitution of the phenyl ring is reported. These compounds constitute a new class of ligands for the synthesis of oligocyclic platinum(II) complexes. In vitro cytotoxicity tests indicate that the most basic amine ligands afford the most effective complexes. Two of the new complexes were more potent against L1210 murine leukemia cells than the well-established antitumor compound cisplatinum.

Strobilurin N and two metabolites related to chorismic acid from the fruit bodies of Mycena crocata (Agaricales).

Strobilurin N (1), a new member of the strobilurin family of antibiotics, has been isolated from the toadstool Mycena crocata, together with dehydrochorismic acid lactone (5) and 3-[1-carboxyvinyl)oxy]benzoic acid (6), which are closely related to chorismic acid (10). Their structures were determined mainly by 1H and 13C NMR spectroscopy. Interestingly, strobilurin N is the first strobilurin without antifungal activity.

Zinc(II) complexes of tripodal peptides mimicking the zinc(II)-coordination structure of carbonic anhydrase.

Two new tripodal peptide ligands with histidine side chains have been synthesized and were shown to form stable zinc(II) complexes. Their NMR and mass spectra indicate a structure that is analogous to the active center of carbonic anhydrase. Both the ligands and the zinc complexes were titrated potentiometrically in order to obtain the pKa values for the coordinated water of the zinc complexes; due to the low solubility of the complexes only estimates could be obtained.

Noroudemansin A, a new antifungal antibiotic from Pterula species 82168 and three semisynthetic derivatives.

A new antifungal (E)-beta-methoxyacrylate noroudemansin A (1), was isolated from cultures of Pterula sp. 82168. Its biological activities were investigated and compared with oudemansin A. The structure was elucidated by spectroscopic methods. Three semisynthetic noroudemansin A derivatives were synthesized from the natural product.

Vismione H and structurally related anthranoid compounds of natural and synthetic origin as promising drugs against the human malaria parasite Plasmodium falciparum: structure-activity relationships.

Natural and synthetic anthranoid compounds were subjected to an evaluation against asexual erythrocytic stages of the human malaria parasite Plasmodium falciparum in vitro. Stimulated by the good activities of Vismia guineënsis extracts, a more detailed investigation of the active principles revealed the pre-nylated preanthraquinone vismione H (1) to be a potent antimalarial [50% growth-inhibitory concentration (IC50) 0.088 microg/ml]. On the basis of this finding a series of chemically related phlegmacins (2-5), flavomannins (6-8), and rufoolivacins (9-11) isolated from several species of Cortinarius, a genus of higher fungi, and 5 synthetic vismione-like anthranoids (12-16) were evaluated as well. Although these compounds displayed weaker antiplasmodial effects than did vismione H (1) itself, considerable levels of activity were obtained with phlegmacin B1 (2), flavomannin-6,6'-di-O-methyl ether A1 (6), trans-4-hydroxy-flavomannin-6,6'-di-O-methyl ether A (8), and rufoolivacin B (10). Initial preconditions for activity within the vismiones and related anthranoids were established.

Strobilurin M, tetrachloropyrocatechol and tetrachloropyrocatechol methyl ether: new antibiotics from a Mycena species.

The antifungal and cytostatic compound strobilurin M (1) is a new variant of the strobilurins produced by Mycena sp. 96097, a tropical basidiomycete. The same fungus was found to produce tetrachloropyrocatechol (3a) and tetrachloropyrocatechol methyl ether (3b), new natural products, which exhibit antifungal, antibacterial and cytotoxic activities.

New botrydial sesquiterpenoids from Hymenoscyphus epiphyllus.

Four new botrydial derivatives, hymendial (1), 7 alpha-hydroxydihydrobotrydial (2), 7 alpha-hydroxy-10-O-methyldihydrobotrydial (4), and 7 alpha-acetoxy-15 alpha-methoxy-10-O-methyl-dihydrobotrydial (5) were isolated together with dihydrobotrydial (3) from the culture fluid of the ascomycete Hymenoscyphus epiphyllus. In addition, cytochalasin H (6a), 18-deoxycytochalasin H (6b) and (+)-mellein (7) were produced by this fungus. Hymendial (1), possessing an alpha, beta-unsaturated dialdehyde functionality, exhibits antimicrobial and cytotoxic activities and is mutagenic in the Ames Salmonella assay.

Two potential indole-3-acetaldehyde dehydrogenases in the phytopathogenic fungus Ustilago maydis.

The phytopathogenic basidiomycetc Ustilago maydis produces indole-3-acetic acid (IndCH2COOH) and indole-3-pyruvic acid (Ind-Prv) from tryptophan. Indole-3-acetaldehyde (IndCH2CH2O) is the common intermediate in the conversion of Ind-Prv and tryptamine to IndCH2COOH. We purified an enzyme (Iad1) from U. maydis that catalyzes the NAD(+)-dependent conversion of IndCH2CH2O to IndCH2COOH and isolated corresponding cDNA and genomic clones. The identity of the cDNA clone was confirmed by expression in Escherichia coli and demonstration of enzymatic activity. In U. maydis, iad1-null mutants were generated by gene replacement. The ability to convert IndCH2CH2O to IndCH2COOH was at least 100-fold reduced in U. maydis iad1-null mutants grown in medium with glucose as carbon source. However, the iad1-null mutants were not diminished in their capacity to produce IndCH2COOH from tryptophan, indicating that IndCH2COOH formation from tryptophan apparently proceeds in the absence of IndCH2CH2O dehydrogenase activity under these conditions. Iad1 expression was strongly induced during growth on ethanol while under these conditions iad1-null mutants were unable to grow. This reveals that iad1 is primarily engaged in the conversion of ethanol to acetate. In iad1-null mutants we detected an additional NAD(+)-dependent IndCH2CH2O dehydrogenase activity that was induced during growth on L-arabinose but repressed in the presence of D-glucose. In arabinose-containing medium the conversion of tryptophan to IndCH2COOH was approximately 5-fold reduced in wild-type strains but 10-15-fold reduced in iad1-null mutant strains compared to IndCH2COOH formation in glucose-containing medium. In addition, the formation of Ind-Prv from tryptophan was abolished in wild-type and iad1-null mutant strains. During growth on arabinose, the conversion of tryptamine to IndCH2COOH was strongly favored suggesting that the glucose-repressible IndCH2CH2O dehydrogenase is required to convert IndCH2CH2O derived from tryptamine to IndCH2COOH.

(+)-10 alpha-Hydroxy-4-muurolen-3-one, a new inhibitor of leukotriene biosynthesis from a Favolaschia species. Comparison with other sesquiterpenes.

A new inhibitor of leukotriene biosynthesis, (+)-10 alpha-hydroxy-4-muurolen-3-one (1), was isolated from fermentations of Favolaschia sp. 87129. Its structure was established by spectroscopic methods. The compound exhibited no antifungal or antibacterial activities. The effects of 1 on leukotriene biosynthesis were compared with (+)-T-cadinol, (-)-3-oxo-T-cadinol, and (+)-3 alpha-hydroxy-T-cadinol, three related sesquiterpenes.

Lactarane type sesquiterpenoids as inhibitors of leukotriene biosynthesis and other, new metabolites from submerged cultures of Lentinellus cochleatus (Pers. ex Fr.) Karst.

Three known sesquiterpenoids of the lactarane and secolactarane type, deoxylactarorufin A (1), blennin A (2) and blennin C (3), have been obtained from cultures of Lentinellus cochleatus (Basidiomycetes) together with the new metabolites (Z)-2-chloro-3-(4-methoxyphenyl)-2-propen-1-ol (4) and lentinellone (5), a protoilludane derivative. The structures were determined by spectroscopic investigations. 1, 2 and 3 are potent inhibitors of leukotriene biosynthesis in rat basophilic leukemia (RBL-1) cells and human peripheral blood leukocytes (PBL).