Macrocyclic Trichothecenes Research Articles

Airborne outbreak of trichothecene toxicosis

A heavy infestation of Stachybotrys atra in a house in suburban Chicago has caused chronic health problems for the members of the household. Extracts of the S. atra contaminated household material proved toxic to animals; from these extracts were isolated several highly toxic macrocyclic trichothecenes. After the contaminated duct work, insulation and building material had been replaced, the members of the household no longer complained of illnesses suggestive of trichothecene toxicosis.

7 alpha-hydroxytrichodermol, a new trichothecene from Myrothecium roridum.

Five plant-pathogenic isolates of Myrothecium roridum from Florida produced only simple trichothecenes rather than the usual macrocyclic trichothecenes. The major metabolite was 7 alpha-hydroxytrichodermol.

Rapid and high resolution capillary supercritical fluid chromatography (SFC) and SFC/MS of trichothecene mycotoxins.

The potential application of capillary column supercritical fluid chromatography (SFC) and SFC/mass spectrometry (SFC/MS) for the separation and analysis of mycotoxins of the trichothecene group was examined. Trichothecenes present significant analytical problems for both gas and liquid chromatography with a major difficulty for the latter being the lack of sufficiently sensitive and selective detectors. Supercritical carbon dioxide mobile phases at temperatures up to 100 degrees C were used with deactivated fused silica columns coated with crosslinked stationary phases. Separations were obtained under pressure ramped conditions using long (15 m) 50-micron i.d. columns for several trichothecenes (diacetoxyscirpenol, deoxynivalenol, and T-2 toxin) and related higher molecular weight macrocyclic (roridin and verrucarin) trichothecenes. In addition, new rapid pressure programming techniques with short (less than 2m) 25- to 50-micron i.d. capillary columns were used to obtain fast separations in as little as 1 min. SFC/MS with ammonia chemical ionization provided high selectivity and sensitive detection (with approximately 1-pg detection limits) for trichothecene mixtures. The extension to complex sample matrices is discussed and the application of selective MS/MS detection is demonstrated.

Preliminary observations on the effects of macrocyclic trichothecenes on plant growth

The biological properties of the macrocyclic trichothecenes roridin A, isororidin E, baccharinol B4, verrucarin A, verrucarin J and trichoverrin B were assayed with etiolated wheat coleoptiles ( Triticum aestivum L.), bean ( Phaseolus vulgaris L.), corn ( Zea mays L.) and tobacco ( Nicotiana tabacum L.). Metabolites were tested from 10 −3 to 10 −8 M in the coleoptile assay and from 10 −2 to 10 −4 M in intact plants. All inhibited coleoptile growth; verrucarins A and J, and trichoverrin B inhibited to 10 −7 M. All induced effects in plants that ranged from chlorosis, necrosis, malformations to stunting.

Macrocyclic trichothecene toxins produced by Stachybotrys atra strains isolated in Middle Europe.

A total of 17 strains of Stachybotrys atra isolated in Hungary and Czechoslovakia were cultured on Sabouraud agar, and the toxins produced by them were chemically analyzed by gas-liquid chromatography, high-pressure liquid chromatography, and mass spectroscopy. Furthermore, brine shrimp (Artemia salina) bioassay was used for the determination of toxicity of the compounds examined. Macrocyclic trichothecenes (satratoxins H and G, roridin E, and verrucarin J as well as two other unidentified macrocyclic trichothecenes) were found in all of the cultures tested. The identities of satratoxins H and G, roridin E, and verrucarin J were qualitatively determined by high-pressure liquid chromatography and gas-liquid chromatography. The ratio of satratoxins H and G and roridin E was found to be similar in each of the strains tested, but the amount of verrucarin J found was different in each of them. One of the unidentified macrocyclic trichothecenes was equivalent to the compound isolated by Harrach et al. (Harrach et al., Appl. Environ. Microbiol. 41:1428-1433, 1981). The other one proved to be a newly isolated macrocyclic trichothecene toxin. Stachybotryotoxicosis, one of the oldest mycotoxicoses known, and a serious problem in Middle Europe (Gy. Danko, Magy. Allatorv. Lapja 31:226-232, 1976), is believed to be caused by macrocyclic trichothecene toxins produced by Stachybotrys atra (R. M. Eppley, in Rodricks et al., ed., Mycotoxins in Human and Animal Health, p. 285-293, 1977). Forty years ago, the death of animals in the Soviet Union was associated with this fungus (C. U. Ruhliada, in Proceedings of the All-Union Sci. and Tech. Conf., p. 47-51, 1980).(ABSTRACT TRUNCATED AT 250 WORDS)

Macrocyclic trichothecenes: Cause of livestock poisoning by the Brazilian plant Baccharis coridifolia

Nine macrocyclic trichothecenes, thought to cause toxic effects in herbivors, were isolated from the Brazilian shrub Baccharis coridifolia. The structures of two new components, named miophytocene A and B, are described. Structure analysis was mainly accomplished by application of two-dimensional Fourier transform NMR techniques. The trichothecenes are most likely produced by the soil fungus Myrothecium verrucaria, which was isolated from soil samples around B. coridifolia. It is concluded that the plant is able to absorb and accumulate these mycotoxins. Histopathological studies on rabbits which received roridin E and A per os revealed mainly necrosis and hemorrhages of the mucosa of the colon and in the case of roridin A also of the caecum. Lethality in mice was generally low, intoxication proceeding slowly. It has to be considered, however, that all trichothecenes tested are practically insoluble in aqueous solutions and were applied as emulsions (i.p. and per os application). No trichothecenes or other toxic substances were detected from the Brazilian species Baccharis dracunculifolia, although slight toxic effects have been reported in cattle.

Myrotoxins: a new class of macrocyclic trichothecenes

An isolate of Myrothecium roridum which is a pathogen on tomatoes in Texas produces a new class of C27 macrocyclic trichothecenes which contains a nonconjugated diene system that includes a vinyl ether group.

Production and characterization of antibody against deoxyverrucarol.

Immunization of rabbits with deoxyverrucarol (DOVE) conjugated to bovine serum albumin resulted in antibodies bound with either tritiated DOVE or diacetoxyscirpenol (DAS), but not with T-2 toxin. The affinity of antibodies with DOVE was found to be much higher than with DAS. When [3H] DOVE was used as a marking ligand in the competitive radioimmunoassay, the concentrations causing 50% inhibition of binding radioactivities by unlabeled DOVE, verrucarol, verrucarin A, and 4-monoacetoxyscirpenol were found to be 0.32, 1,070, 9,500, and 10,000 ng per assay, respectively. T-2 toxin, 15-monoacetoxyscirpenol, and deoxynivalenol gave less than 20% inhibition at 10 micrograms per assay. However, when [3H] DAS was used as the marking ligand, the concentrations causing 50% inhibition by DOVE, DAS, and verrucarol were found to be in the 50 to 60 ng per assay range. The antibodies are thus highly specific to DOVE rather than a common trichothecene backbone. The possible use of this antiserum for assay of macrocyclic trichothecenes is discussed.

Further Syntheses of Optically Active Verrucarinic Acid, 43rd Communication of Verrucarins and Roridins

AbstractTwo new syntheses of verrucarinic acid (2S, 3R‐dihydroxy‐3‐methylpentanoic acid) and its derivatives, suitably protected for the further conversion to macrocyclic trichothecenes, are described. The first one makes use of a diastereoselective alkylation of a (−)‐(S)‐malic acid ester and the regioselective reductin of one carboxyl function toa methyl group. The second approach involves a stereoselective addition of an allylsilane to a chiral glyoxylate.

Toxicological features of T-2 toxin and related trichothecenes

Toxicological characteristics of T-2 toxin and related trichothecenes, mycotoxins produced by Fusarium, Trichoderma, Verrucaria, and others, were investigated in regard to LD50 values, dermal toxicity, hematological changes, and tumorigenicity. The LD50 values (mg/kg) of T-2 toxin in adult male mice were po 10.5, ip 5.2, sc 2.1, and iv 4.2, and those of nivalenol were ip 4.1 and iv 6.3. These data showed that the lethal toxicity of T-2 toxin and nivalenol was about 10 times higher than deoxynivalenol. Newborn and immature animals were much more susceptible than adults. Inhalation experiments with T-2 toxin revealed that 33 ppb T-2 toxin for 160-min and 140 ppb T-2 toxin for 30-min exposure were enough to cause death in mice within several days. The dermal toxicity of T-2 toxin and macrocyclic trichothecenes (verrucarin A and roridin A) was significantly higher than the other trichothecenes, and the induction of edema and other dermal toxicities is caused by direct attack of the trichothecenes on the capillary vessels. No tumorigenicity of fusarenon-X to dermal tissues was shown in mice. Pretreatments of mice with SH-compounds, prednisolon, phenobarbital, and 3-methylcholanthrene did not change the LD50 value of T-2 toxin.

Miotoxin-A: A Novel Macrocyclic Trichothecene from the Brazilian Plant Baccharis coridifolia / Miotoxin-A, Trichothecene, Compositae. Poisonous Plants, NMR -and X -Ray Structure Analysis

The isolation of Miotoxin-A*, a novel macrocyclic trichothecene from Baccharis coridifolia DC. (Compositae) is described. The structure has been determined to be 4-hydroxy-roridin E by means of NMR-spectroscopy and X-ray structure analysis

Antileukemic compounds derived by chemical modification of macrocyclic trichothecenes. 2. Derivatives of roridins A and H and verrucarins A and J.

Various 8 beta-hydroxy, 16-hydroxy, and 9 beta,10 beta-epoxy derivatives of roridins A and H and verrucarins A and J have been prepared and tested in vivo against P388 mouse leukemia. The 9 beta,10 beta-epoxy derivatives and 16-hydroxy derivatives consistently exhibit very high activity. The 8 beta-hydroxy-9 beta,10 beta-epoxy and 16-hydroxy-9 beta,10 beta-epoxy derivatives of verrucarin A and roridin A exhibit extraordinary activity against P388. The 8 beta-hydroxy-9 beta,10 beta-epoxy and 16-hydroxy-9 beta,10 beta-epoxy derivatives of verrucarin A and roridin A exhibit extraordinary against P388.

ChemInform Abstract: MACROCYCLIC AND OTHER NOVEL TRICHOTHECENES: THEIR STRUCTURE, SYNTHESIS, AND BIOLOGICAL SIGNIFICANCE

Chemischer InformationsdienstVolume 14, Issue 20 Reviews ChemInform Abstract: MACROCYCLIC AND OTHER NOVEL TRICHOTHECENES: THEIR STRUCTURE, SYNTHESIS, AND BIOLOGICAL SIGNIFICANCE B. B. JARVIS, B. B. JARVISSearch for more papers by this authorE. P. MAZZOLA, E. P. MAZZOLASearch for more papers by this author B. B. JARVIS, B. B. JARVISSearch for more papers by this authorE. P. MAZZOLA, E. P. MAZZOLASearch for more papers by this author First published: May 17, 1983 https://doi.org/10.1002/chin.198320335Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume14, Issue20May 17, 1983 RelatedInformation

Syntheses of Optically Active Verrucarinic Acid. 40th Communication on Verrucarins and Roridins

AbstractThree syntheses of (2S, 3R)‐2,5‐dihydroxy‐3‐methylpentanoic acid (verrucarinic acid) and its derivatives suitably protected for the further transformation to macrocyclic trichothecenes are described. These involve an enantioselective ester hydrolysis by pig liver esterase, a Sharpless epoxidation and an asymmetric hydroboration.

Macrocyclic and other novel trichothecenes: their structure, synthesis, and biological significance

Macrocyclic and other novel trichothecenes: their structure, synthesis, and biological significance

Identification of “Water-Soluble” Toxins Produced by a Stachybotrys atra Strain from Finland

Toxins of a Stachybotrys atra strain from Finland proved to be soluble in a simulated gastrointestinal system. They were purified and characterized as satratoxin H, satratoxin G, and an unknown macrocyclic trichothecene with a molecular ion of 528.

Macrocyclic trichothecene toxins produced by a strain of Stachybotrys atra from Hungary.

A strain of Stachybotrys atra isolated from a field case of stachybotryotoxicosis in Hungary was cultured in Hungary. All of the compounds toxic to brine shrimp were separated from the culture extract by solvent partition, column chromatography, and preparative thin-layer chromatography. Two of the toxic compounds were identified as verrucarin J and satratoxin H by comparison with pure standards resolved by high-pressure liquid chromatography and characterized by mass spectrometry. Two other toxic components were identified as roriden E and satratoxin G on the basis of their mass spectra. The fifth toxic compound was identified as a macrocyclic trichothecene based on the following findings: a positive 4-(p-nitrobenzyl)pyridine color reaction, hydrolysis resulting in verrucarol verified by combined gas chromatography-mass spectrometry, and a characteristic trichothecene proton-nuclear magnetic resonance spectrum. This macrocyclic trichothecene has a molecular ion (528) identical to satratoxin H, and its mass spectrum is similar; however, its Rf value on Silica Gel G differs.

Partial Synthesis of 3′‐Hydroxy‐2′‐deoxy‐2″,3″,4″,5″‐tetrahydroverrucarin A. Verrucarins and roridins, 38th Communication [1

AbstractThe macrocyclic trichothecene triester 3′‐hydroxy‐2′‐deoxy‐2",3",4",5"‐tetrahydroverrucarin A (37), has been synthesized starting from the sesquiterpene alcohol verrucarol (3), adipic acid and a derivative of mevalonic acid (14). The latter has been prepared from 4‐(tetrahydro‐2‐pyranyloxy)‐2‐butanone (9).

Antileukemic compounds derived from the chemical modification of macrocyclic trichothecenes. 1. Derivatives of verrucarin A.

Verrucarin A (2) was epoxidized to give the beta-9,10-epoxide 7 (major product) and alpha-9,10-epoxide 9 (minor product). The beta-epoxide 7 and its acetate 8 exhibit high in vivo antileukemic activity against P-388 mouse leukemia, whereas 2 and 9 are inactive. Epoxidation of verrucarin B (3) and roridin A (1) to their respective beta-9,10-epoxides (11 and 12, respectively) also yields compounds with substantially increased activity. Allylic alcohols derived from 2, alpha-C8 (20), beta-C8 (14), and C16 (15), were synthesized and tested; only 15 exhibited substantial in vivo activity.