Cyclopaldic Acid Research Articles

Cyclopaldic acid, a major phytotoxic metabolite of Seiridium cupressi, the pathogen of a canker disease of cypress

A phytotoxic substance was produced in vitro in a relatively high concentration (c. 40 mg/1) by Seiridium cupressi, a fungus that causes a canker disease of cypress (Cupressus sempervirens) and other Cupressaceae in Greece and in other parts of the world. Structural investigations demonstrated that the substance was identical with cyclopaldic acid, an antibiotic known to be a metabolite of some species of Penicillium, Aspergillus and Pestalotiopsis. Absorbed by severed twigs of three species of Cupressus and by cuttings of two herbaceous non‐host plants (tomato and mung bean), cyclopaldic acid at concentrations of 10‐100 ug/ml induced leaf chlorosis and necrosis. Oat seed germination and root growth of oat seedlings were also reduced to about 50% at 75 and 100 jig/ml, respectively. The compound showed antifungal activity towards species of Botrytis. Fusarium and Geotrichum when assayed at a concentration range from 10 to 100 /ug ml. We believe this to be the first report of cyclopaldic acid as a non‐selective fungal phytotoxin. However, its possible role in the pathogenesis of the cypress canker disease has not been established.

Xylaral, ein Hydroxyphthalid‐Derivat aus Fruchtkörpern von Xylaria polymorpha (Ascomycetes)

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.

Terverticillate Penicillia: Chemotaxonomy and Mycotoxin Production

A total of 4346 isolates of terverticillate Penicillium species was examined for production of my? cotoxins and other important secondary metabolites. Nearly all taxa and chemotypes (38 in all) produced one or more known mycotoxins consistently. Profiles of secondary metabolites were specific for each taxon, but several mycotoxins were produced by more than one species, suggesting a high degree of relatedness in the terverticillate penicillia. A high number of misidentified Penicillium isolates were reidentified, clarifying connections between taxa and profiles of mycotoxins and other secondary me? tabolites. Confirmed production of several mycotoxins in different taxa is reported for the first time. Penicillium chrysogenum, P. atramentosum, P. coprophilum, P. crustosum, P. expansum, P. glandicola var. glandicola and var. glaucovenetum, P. griseofulvum, P. hirsutum var. hirsutum, var. albocoremium, var. allii and var. hordei, and P. vulpinum are reported for the first time to be consistent producers of roquefortine C. Griseofulvin is reported from P. coprophilum. Tremorgen penitrem A was consistently produced by P. crustosum, P. glandicola var. glandicola and P. clavigerum. Terrestric acid is reported from P. hirsutum and its varieties, and P. crustosum. P. hirsutum var. hirsutum and P. solitum produce compactin. Penicillium mononematosum produces cyclopaldic acid and isochromantoxin. P. expansum was found to produce the mycotoxin chaetoglobosin C and P. atramentosum produces rugulovasine A. Several new varieties, chemotypes and combinations are proposed, based on profiles of secondary metabolites, morphology and physiological characters. Living ex type and authentic cultures of taxa believed to be synonyms of important species were examined and revised lists of synonyms are pre? sented.

Terverticillate Penicillia: Chemotaxonomy and Mycotoxin Production

A total of 4346 isolates of terverticillate Penicillium species was examined for production of mycotoxins and other important secondary metabolites. Nearly all taxa and chemotypes (38 in all) produced one or more known mycotoxins consistently. Profiles of secondary metabolites were specific for each taxon, but several mycotoxins were produced by more than one species, suggesting a high degree of relatedness in the terverticillate penicillia. A high number of misidentified Penicillium isolates were reidentified, clarifying connections between taxa and profiles of mycotoxins and other secondary metabolites. Confirmed production of several mycotoxins in different taxa is reported for the first time. Penicillium chrysogenum, P. atramentosum, P. coprophilum, P. crustosum, P. expansum, P. glandicola var. glandicola and var. glaucovenetum, P. griseofulvum, P. hirsutum var. hirsutum, var. albocoremium, var. allii and var. hordei, and P. vulpinum are reported for the first time to be consistent producers of roquefortine C. Griseofulvin is reported from P. coprophilum. Tremorgen penitrem A was consistently produced by P. crustosum, P. glandicola var. glandicola and P. clavigerum. Terrestric acid is reported from P. hirsutum and its varieties, and P. crustosum. P. hirsutum var. hirsutum and P. solitum produce compactin. Penicillium mononematosum produces cyclopaldic acid and isochromantoxin. P. expansum was found to produce the mycotoxin chaetoglobosin C and P. atramentosum produces rugulovasine A. Several new varieties, chemotypes and combinations are proposed, based on profiles of secondary metabolites, morphology and physiological characters. Living ex type and authentic cultures of taxa believed to be synonyms of important species were examined and revised lists of synonyms are presented.

Stoffwechselprodukte von Mikroorganismen, XXVII[1] Cyclopaldsäure und 3-O-Methyl-cyclopolsäure, zwei antibiotisch wirksame Substanzen aus Aspergillus duricaulis/Investigations on Metabolites of Microorganisms, XXVII [1] Cyelopaldic Acid and 3-O-Methyl Cyclopolic Acid, Two Antibiotically Active Substances from Aspergillus duricaulis

Abstract 3,5-Dihydroxy-4-formyl-7-methoxy-6-methyl-1(3H)-isobenzofuranone [=cyclopaldic acid] (1) and 5-hydroxy-4-hydroxymethyl-3,7-dimethoxy-6-methyl-1(3H)-isobenzofura-none [= 3-O-methyl cyclopolic acid] (2) were isolated from Aspergillus duricaulis-, those compounds were found to be antibiotically active.

Metabolic products of microorganisms

In the course of a screening for new metabolites from fungi we isolated a substance with antimicrobial activity from cultures of Aspergillus duricaulis (CBS 481.65) (Tü 679). It was antagonized by putrescine, spermidine, spermine, arginine, citrulline, lysine, ornithine, in higher concentration by aspraagine and glutamine too. The effect of ethylenediaminetetraacetate on the susceptibility of Streptomyces viridochromogenes (Tü 57) and Bacillus subtilis ATCC 6051 to this antibiotic has been studied. The substance was characterized and identified as cyclopaldic acid.

Gladiolic acid and related aromatic ortho-dialdehydes, a novel class of mitochondrial inhibitors. Inactivation of cytochrome c

Gladiolic acid (4-methoxy-5-methyl-o-phthalaldehyde-3-carboxylic acid), an antifungal metabolite produced by Penicillium gladioli (McCull. & Thom), was found to inactivate the catalytic properties of horse heart cytochrome c by reacting with functionally-critical lysine residues in the heme protein. Cyclopaldic acid, quadrilineatin, flavipin and 3-formylopianic acid, aromatic o-dialdehydes structurally related to gladiolic acid (GA), also inactivated cytochrome c. Dihydrogladiolic acid did not complex with cytochrome c. Three moles of GA reacted per mole of cytochrome c reduced the ability of the protein to function with beef heart cytochrome oxidase and pig heart NADH-cytochrome c reductase by 85% and 100%, respectively. The ferricytochrome c-GA complex weakly inhibited the interaction of ferrocytochrome c with the acidic protein of cytochrome oxidase. The reaction between GA and cytochrome c appeared to proceed further than a simple Schiff base formation and the complex was not reversed by dialysis. Gladiolic acid acted as an “apparent” inhibitor of cytochrome oxidase of sweet potato mitochondria by inactivating cytochrome c in situ . Oxidative phosphorylation associated with cytochrome oxidase activity (Site III) was strongly inhibited.

173. Studies in relation to biosynthesis. Part XXII. Palitantin and cyclopaldic acid

173. Studies in relation to biosynthesis. Part XXII. Palitantin and cyclopaldic acid