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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.

The stem and leaves of Gasteria bicolor afforded three new dihydroanthracenones namely 3,4-dihydro-2,6,9-trihydroxy-8-methyl-1(2H)-anthracenone (gasteriacenone A), 3,4-dihydro-2,4,9-trihydroxy-6-methoxy-8-methyl-1(2H)-anthracenone (gasteriacenone B) and 3,4-dihydro-4,6,9-trihydroxy-7-carbomethoxy-8-methyl-1(2H)-anthraceno ne (gasteriacenone C). Their structures were determined by spectroscopic methods including 2D NMR techniques.

Two new xanthocillin type antibiotics, darlucin A (1) and B (2), were isolated from fermentations of Sphaerellopsis filum (Darluca filum). Their structures were established by spectroscopic methods. The darlucins are the first known compounds with a 1,2-diisocyanoalkene moiety. Both compounds exhibited antibacterial, antifungal and weak cytotoxic activities.

In a search for new inhibitors of RNA-directed DNA-polymerases kuehneromycin A (1) was isolated from fermentations of a Tasmanian Kuehneromyces species. Its structure was elucidated by spectroscopic methods. Kuehneromycin A (1) is a non-competitive inhibitor of avian myeloblastosis virus (Ki 200 microM) and moloney murine leukemia virus (Ki 40 microM) reverse transcriptases. The second compound, kuehneromycin B (2) is a strong inhibitor of platelet aggregation stimulated with different inducers. In addition, both compounds exhibit cytotoxic and antimicrobial activities.

A new salicylic acid derivative, caloporoside, was isolated from fermentations of Caloporus dichrous. Its structure was elucidated by a combination of chemical and spectroscopic methods. Caloporoside exhibits weak antibacterial and antifungal activities and is a quite selective inhibitor of phospholipase C isolated from pig brain (Ki 12, 3 microM).

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.

In a search for inhibitors of RNA-directed DNA polymerases a new isolactarane sesquiterpenoid, hyphodontal (1), was isolated from fermentations of a Canadian Hyphodontia species. Its structure was elucidated by spectroscopic methods. Hyphodontal strongly inhibits the growth of several yeasts and is a non-competitive inhibitor of avian myeloblastosis virus (Ki 346 microM) and Moloney murine leukemia virus (Ki 112 microM) reverse transcriptases. In addition, cytotoxic and antifungal activities were observed.

Six novel enzyme inhibitors of RNA-directed DNA-polymerases of human immunodeficiency-, avian myeloblastosis and murine leukemia viruses were isolated from fermentations of a canadian Mniopetalum species. They were named mniopetals A, B, C, D, E and F. Their structures were elucidated by spectroscopic methods. The compounds, in addition to their inhibitory activities on reverse transcriptases, exhibit antimicrobial and cytotoxic properties.

A new hirsutane derivative, phellodonic acid (1), has been isolated from fermentations of Phellodon melaleucus strain 87113. Its structure was elucidated by spectroscopic methods. The compound exhibits antibiotic activities towards bacteria and fungi. 1 is the first bioactive metabolite from cultures of a species belonging to the family Thelephoraceae.

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.

Tyromycin A, a new inhibitor of leucine and cysteine aminopeptidases has been isolated from mycelial cultures of the basidiomycete Tyromyces lacteus (Fr.) Murr. Its structure was established as 1,16-bis-[4-methyl-2,5-dioxo-3-furyl]hexadecane (1) by spectral analysis and transformation into ester and imide derivatives.

A novel inhibitor of RNA-directed DNA-polymerases was isolated from fermentations of Clavicorona pyxidata. Its structure was elucidated by spectroscopic methods. Clavicoronic acid (1) is a noncompetitive inhibitor of avian myeloblastosis virus (Ki 130 microM) and Moloney murine leukemia virus (Ki 68 microM) reverse transcriptases. In permeabilized cells and isolated nucleic DNA- and RNA-synthesis are not affected. Clavicoronic acid markedly inhibits the multiplication of vesicular stomatitis virus in baby hamster kidney cells by interfering with this virus's RNA-directed RNA-polymerase. 1 exhibits no cytotoxic and very weak antimicrobial activities.

A new triterpene and its glycosides were isolated from the bark of Schefflera octophylla together with asiatic acid and asiaticoside. Based on spectroscopic data, especially 2DNMR, and chemical transformations the structures of the new compounds were determined as 3 alpha-hydroxy-urs-12-ene-23,28-dioic acid and 3 alpha-hydroxy-urs-12-ene-23,28-dioic acid 28-O-[alpha-L-rhamnopyranosyl (1----4)-O-beta-D-glucopyranosyl (1----6)]-beta-D-glucopyranoside. For the first time asiaticoside was isolated from a plant other than Centella asiatica.

Omphalone, a new antibiotic, cytotoxic, and phytotoxic pigment has been isolated from fermentations of a Canadian strain of Lentinellus omphalodes. Its structure has been established as 2-(4-methylfuran-2-yl)-1,4-benzoquinone (1) by spectroscopic investigations and conversion into leuco-acetate 2.

A novel enzyme inhibitor of RNA-directed DNA-polymerases of avian myeloblastosis and murine leukemia virus was isolated from fermentations of an tasmanian Podoscypha species. Its structure was elucidated by spectroscopic methods and oxidative degradation as (E)-4,5-dioxo-2-hexadecenoic acid (1). The enzyme inhibitor, which was named podoscyphic acid, did not inhibit DNA and RNA synthesis in permeabilized L 1210 cells nor did it affect RNA synthesis in isolated nuclei of L 1210 cells. 1 inhibits protein synthesis in whole L 1210 cells and rabbit reticulocyte lysate and shows very weak antimicrobial and cytotoxic properties. The testing of ethyl (E)-4,5-dioxo-2-hexadecenoate (2) and (E)-4-oxo-2-tetradecenoic acid (11) revealed the importance of the free gamma-oxoacrylic acid unit for the biological activities of 1.

In addition to 3-epi-betulinic acid, three triterpene glycosides were isolated from leaves of Schefflera octophylla. The structures of the glycosides have been determined as 28-O-[alpha-L-rhamnopyranosyl(1----4)-O-beta-D-glucopyranosyl(1----6)-be ta-D- glucopyranosides of 3 alpha-hydroxy-lup-20(29)-ene-23,28-dioic acid, 3 alpha,11 alpha- dihydroxy-lup20(29)-ene-23,28-dioic acid and 3-epi-betulinic acid by spectroscopic data and chemical transformations. The last two compounds were found for the first time in the plant kingdom.

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.

Strobilurin D and strobilurin F, two new cytostatic and antifungal antibiotics of the (E)-beta-methoxyacrylate class, have been isolated from mycelial cultures of the basidiomycete Cyphellopsis anomala (Pers. ex Fr.) Sing. The structures were elucidated by spectroscopic methods. The antibiotics inhibit the growth of human and animal cells and a wide variety of fungi. Like strobilurins A and B, the new metabolites are potent inhibitors of respiration.

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.

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.

Three new antibiotics, merulinic acids A, B, and C, have been isolated from fruiting bodies of Merulis tremellosus and Phlebia radiata. They are closely related derivatives of beta-resorcylic and salicylic acid, carrying monounsaturated C17-alkyl side chains in 6-position. The merulinic acids are mixtures of the delta8'-compounds with minor amounts of the corresponding delta10'-, dehydro, and dihydro derivatives, separable only by means of HPLC. delta8'-Merulinic acid A (I) was synthesized via a biomimetic cyclization of a linear precursor. The merulinic acids inhibit a variety of bacteria and are not active against fungi. RNA, DNA, and protein synthesis in Bacillus brevis and Ehrlich carcinoma ascites cells are inhibited shortly after the addition of the antibiotics. Almost complete hemolysis of human erythrocytes is caused by 25 microgram/ml of merulinic acid B and C or by 73 microgram/ml of merulinic acid A.

Phlebiakauranol aldehyde and the corresponding alcohol were isolated from cultures of Punctularia atropurpurascens. The aldehyde but not the alcohol exhibited strong antifungal activity against several phytopathogens as well as antibacterial and cytotoxic activities. Two acetylated derivatives prepared from the aldehyde showed only very weak antifungal and antibacterial and moderate cytotoxic activities. We therefore assume, that the aldehyde group together with the high number of hydroxyl groups are responsible for the biological activity of the compound.

A crystalline antibiotic, which we have named crinipellin, was isolated from submerged cultures of the basidiomycete Crinipellis stipitaria, strain No. 7612. High resolution mass spectrometry yielded the formula C22H28O5. The antibiotic is most active against Gram-positive bacteria, although yeasts and filamentous fungi are affected to a lesser extent. Crinipellin exhibits high in vitro inhibitory activity against the ascitic form of EHRLICH carcinoma. The incorporation of precursors of DNA-, RNA-, and protein syntheses in EHRLICH carcinoma (and in Bacillus brevis) cells was completely inhibited at 5(10) microgram/ml. In Bacillus brevis the inhibition of the incorporation of uridine was found to be due to an interference by crinipellin with the transport of the precursor into the cells.

From submerged cultures of the marine basidiomycete Halocyphina villosa we isolated siccayne (4-(2,4-dihydroxyphenyl)-2-methyl-1-buten-3-yne) (1), a metabolite first described from fermentations of the deuteromycete Helminthosporium siccans. Siccayne is a moderately active antibiotic, which inhibits Gram-positive bacteria and some fungi at concentrations of 10 approximately 50 micrograms/ml. Its cytotoxic effect is much more pronounced on both normal and Rous-sarcoma-virus transformed chicken embryo fibroblasts as compared to cells of the Ehrlich ascites carcinoma. Siccayne apparently interferes with the uptake of nucleoside precursors into eucaryotic cells as well as with the in vitro incorporation of nucleotides into DNA and RNA.

The strobilurins are two antifungal antibiotics which were isolated from the mycelium of Strobilurus tenacellus strain No. 21602. The strobilurins A and B are highly active against yeasts and filamentous fungi. In vitro antitumor activity was tested using cells of the ascitic form of EHRLICH carcinoma. The strobilurins strongly inhibited the incorporation of radioactive leucine, uridine, and thymidine into the acid-insoluble fraction of cells (protein, RNA, and DNA). The molecular formulas as determined by high resolution mass spectrometry are C16H18O3 for strobilurin A and C17H19C1O4 for strobilurin B.

Scorodonin (1), a novel biologically active metabolite, was isolated from submerged cultures of the mushroom Marasmius scorodonius (FR.) FR. Its structure has been determined by chemical and physical methods. The antibiotic inhibits the growth of bacteria, yeasts, and filamentous fungi. In cells of the ascitic form of EHRLICH carcinoma the incorporation of thymidine and uridine into DNA and RNA is strongly inhibited by scorodonin whereas the incorporation of leucine into protein is not affected.

6-Methylpurine, 6-methyl-9-beta-D-ribofuranosylpurine and 6-hydroxymethyl-9-beta-D-ribofuranosylpurine were isolated from mycelial cultures of Collybia maculata and their antifungal, cytotoxic and antiviral activities investigated. This is the first report on the natural occurrence of these compounds.

Merulidial, a new antibiotic, was isolated from the culture fluid of the Basidiomycete Merulius tremellosus Fr., strain No. WQ 568. Merulidial inhibits a variety of bacteria and fungi. In cells of the ascitic form of EHRLICH carcinoma, DNA synthesis is inhibited at lower concentration as compared to RNA and protein synthesis. Merulidial shows mutagenicity when incubated with the his-mutant TA 100 for Salmonella typhimurium (B.N.AMES). The molecular formula as determined by high resolution mass spectrometry is C15H20O3.

Aleurodiscal, an antifungal antibiotic has been isolated from mycelial cultures of Aleurodiscus mirabilis (Berk. & Curt.) Höhn. It causes abnormal apical branchings of Mucor miehei hyphae at very low concentrations. The structure and absolute configuration of the antibiotic has been determined by a single crystal X-ray analysis and hydrolysis to D-(+)-xylose. Aleurodiscal is a hydroxysesterterpene aldehyde beta-D-xyloside with a novel carbon skeleton.

From mycelial cultures of Oudemansiella mucida a crystalline optically active antibiotic, oudemansin (2), has been isolated; its structure is closely related to strobilurin A (1). The relative configuration of oudemansin have been determined by X-ray analysis. The antibiotic exhibits strong antifungal properties and inhibits respiration in fungi, cells of the ascitic form of EHRLICH carcinoma, and rat liver mitochondria.

A new antimicrobial and cytotoxic sesquiterpenoid, lentinellic acid, has been isolated from submerged cultures of Lentinellus ursinus and L. omphalodes. The structure of the antibiotic was elucidated by spectroscopic methods and a single crystal X-ray analysis. 1 may be formed biogenetically by condensation of a protoilludane aldehyde 4 with a malonate unit.

Two new antifungal (E)-beta-methoxyacrylates, strobilurin C and oudemansin B, were isolated from cultures of Xerula longipes and Xerula melanotricha. Their structures were elucidated by spectroscopic methods. Both antibiotics inhibit the growth of a wide variety of saprophytic and phytopathogenic fungi at very low concentrations. Like strobilurins A, B, and oudemansin A the new metabolites are potent inhibitors of respiration.

Two antimicrobial and cytotoxic metabolites were isolated from fermentation broth of Marasmius alliaceus. The structures of the two crystalline antibiotics, alliacols A (6) and B (1) were elucidated by spectroscopic methods and chemical correlation with alliacolide (3). The alliacols show weak antibacterial and antifungal activity. Both antibiotics strongly inhibit DNA synthesis in cells of the ascitic form of Ehrlich carcinoma at concentrations of 2 approximately 5 microgram/ml. Both alliacols A and B react with cysteine to form adducts with strongly reduced biological activities.

Pilatin, a new marasmane derivative, was isolated from fermentations of the cyphelloid fungus Flagelloscypha pilatii. Its structure was determined by chemical and physical methods. Pilatin inhibits the growth of bacteria and fungi at concentrations of 5-50 micrograms/ml. The compound is highly cytotoxic. The incorporation of thymidine and uridine into DNA and RNA in Ehrlich carcinoma ascitic cells is strongly inhibited by pilatin. Like marasmic acid pilatin causes frameshift mutations in Salmonella typhimurium TA98.

The mutagenic activity in the Ames' Salmonella assay, the antimicrobial activities against bacteria, fungi, and algae, the cytotoxic activities against Ehrlich ascitic tumor cells and L1210 cells, and the phytotoxic activities against Lepidium sativum and Setaria italica, of the unsaturated dialdehyde merulidial and six acetylated, hydroxylated, and cyclopropane ring isomerized derivatives of merulidial, are compared. Some possible structure-activity relationships are discussed.

From submerged cultures of Lachnella villosa, Lachnella sp. 541, and Peniophora laeta we isolated marasmic acid (1), a metabolite first described from surface cultures of Marasmius conigenus. The sesquiterpenoid exhibits potent antimicrobial and cytotoxic properties. In cells of the ascitic form of Ehrlich carcinoma RNA and DNA syntheses are preferentially inhibited. Marasmic acid inhibits RNA synthesis in isolated nuclei, but does not interfere with the transport of nucleoside precursors into the cells. RNA polymerase II and capping enzyme (mRNA guanylyltransferase), two enzymes of nucleic acid metabolism, are markedly affected after preincubation with marasmic acid. We assume that marasmic acid acts on nucleic acid syntheses by direct inhibition of some of the enzymes involved. This mode of action would also explain its mutagenic properties. The preparation and testing of two derivatives, 2 and 3, revealed that the alpha,beta-unsaturated aldehyde is essential for the antimicrobial and cytotoxic activity of marasmic acid.