Trichothecenes

Trichothecenes are a family of over 200 mycotoxins causing a significant economic impact on cereal and grain crops each year. In fact, they may accumulate in infected 

THREE-MEMBERED HETEROCYCLIC RINGS AND THEIR FUSED DERIVATIVES 

D trichothecenes have an additional ring linking the C-4 and C-15 position (e.g., verrucarin A, and roridin A). 

Although this classification system has been largely used, there are other structural features that are not accounted for with this system. For example, all Fusarium trichothecenes, including lype A and Type B, have a hydroxyl or an acetyl group at C-3. Trichothecenes produced by Trichoderma, Trichothecium, Myrothecium, or Stachybotrys, including lypes A, B, C, and D, lack an oxygen function at the C-3 position. 

Two years earlier, glutinosin was isolated by the Butterwick (later Akers) Laboratories of Imperial Chemical Industries Ltd. from Myrothecium verrucaria. After this, glutinosin was identified as a mixture of verrucarins A (380) and B (381). Trichothecenes are produced by a number of different fungal genera such as 

Fusarium, Myrothecium, Stachybotrys, Cylindrocarpon, Verticinimonosporium, Phomopsis, Trichoderma, and Cephalosporium 306, 307). Selected fungi are shown in Fig. 8.2 308-311). 

Erase et al.. The Chemistry of Mycotoxins, Progress in the Chemistry of Organic Natural Products, Vol. 97, DOI 10.1007/978-3-7091-1312-7 8, 

All trichothecenes include the tricyclic 12,13-epoxytrichothec-9-ene core, 370. Based on this structure and its substitution pattern, the mycotoxins have been classified into four types, A (371), B (372), C (373), and D (374), by Ueno et al. Type A (371) can have a hydroxy group, an ester, or no functional group at C-8. Type B (372) possesses a carbonyl group at C-8, type C (373) has an epoxide function at C-7/C-8, and type D (374) mycotoxins are macrocyclic trichothecenes. Included among these four types there are some exceptions, which cannot be grouped accurately using this classification. Other classification systems for trichothecenes were proposed by Jarvis et al. (312) and Tamm et al. (313), but these will not be further discussed in this volume (Fig. 8.3). 

To date, only a few total syntheses of trichothecenes have been published, such as the non-macrocycHc trichothecenes trichodermin (375), anguidine (376), and sporol (377). Examples of the synthesis of macrocyclic trichothecenes are for roridin E (378), baccharin B5 (379), and vemicarin A (380) (Fig. 8.4). 

mompa have led to the isolation of some phenols that are probable precursors of the quinone. 

As mentioned previously (Section 4.4.2), Ireland had noted early on that increasing the number of alkyl substituents at Cl and/or C6 of the allyl silyl ketene acetal resulted in an increase in the rate of rearrangement. Although not investigated by Ireland, the obvious extension of the trend would be that rearrangement of ketene acetals bearing disubstitution at both Cl and C6 would afford vicinal 4° centers. 

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This same experimental approach can be used to determine the appHcabiUty of the aDAS—AP to a competitive assay for DAS. As shown in Eigure 6, increasing amounts of free DAS were used to define the 50% inhibition level (ID q) of DAS for binding of two aDAS—AP conjugates to immobilized DAS. This approach was also used to determine the sensitivity of an EIA, as well as the specificity of the assay, as shown in Table 2. Increasing amounts of trichothecene mycotoxins closely related to DAS were added to microtiter plate wells containing a constant amount of prereacted DAS—aDAS—AP. After 30 min, excess toxin and any free toxin—aDAS—AP were washed out, and substrate was added. Quantification of the color produced was directly related to the abihty of the added toxin to displace aDAS—AP from the immobilized DAS, which is an indication that the aDAS also has an avidity for that toxin. 

Reagent for Epoxides e.g. trichothecene-mycotoxins [1 — 6] valepotriates [7,17] Olefins, acetylene derivatives [8] 4-Hydroxycumarin, anthraquinone [8] Alkylating agents [9-12] NOz... 

Note Trichothecenes and valepotriates only react when there is an epoxy group present in the molecule their detection limits are in the range 25—200 ng substance per chromatogram zone [1]. The detection limits for acetylene derivatives are 100— 800 ng substance per chromatogram zone, but not all give a positive reaction [8]. 

Group 2 includes some 80 sesquiterpene trichothecenes, which are particularly associated with fungi belonging to the group Fusarium. Fusarium species are widely known both as plant pathogens and contaminants of stored foods snch as maize. Trichothecenes are strong inhibitors of protein synthesis in mammalian cells. There have been many incidents of poisoning of farm animals cansed by contamination of their food by these componnds. 

However, the most interesting of the Baccharis species is most certainly B. coridifolia. This plant is well-known in Brazil as being one of that country s most toxic plants (49) and is a serious hazard to livestock who graze in pastures populated by B. coridifolia (49). Four separate collections were made of B. coridifolia (48). Three of these collections were "From several miles outside Curitaba and a fourth collection in a pasture near Santa Maria, the site of an earlier collection of 13. coridifolia (47), and several hundred miles away from Curitaba. ThTs latter collection and two of the three former collections contained appreciable quantities of roridins A and E. A third collection from near Curitaba appeared to contain no macrocyclic trichothecenes. From a 20 g sample of one of the collections of B. coridifolia... 

Our most recent work with B megapotamica has been with the isolation of large quantities of baccharinoids from a 1800 Kg collection. The workup of the crude extract (ca. 30 Kg of black tarry material) of this plant material was conducted by Dr. Fred Boettner of Polyscience, Inc. This near Herculean task required tremendous quantities of solvents, column packings and time to complete. An outline of the fractionation scheme is presented in Figure 2. Fractions F6-F11 contain a large number of baccharinoids. To date, we have characterized over twenty macrocyclic trichothecenes found in B mega-... 

Ueno, Y. (ED) "Trichothecenes - Chemical, Biological, and Toxicological Aspects" Kodensha Scientific, Tokyo, 1983. 

Soil microorganisms produce many compounds that are potentially toxic to higher plants. Examples include members of the following antibiotics (1-6), fatty and phenolic acids (7-12), amino compounds (13-15), and trichothecenes (16, 17). "Soil sickness" and "replant problems" have been reported where certain crops or their residues interfere with establishment of a subsequent crop (18, 19). Toxins resulting from microbial activity sometimes are involved, but it is often unclear whether these are synthesized de novo in microbial metabolism or are breakdown products of the litter itself (20). 

Of four basic trichothecene groups (A, B, C and D), types A and B represent the most important mycotoxins. Type A includes the T-2 toxin that can suppress the immune system and can cause damage to bone marrow. The T-2 toxin is about 14 times more toxic than the most widespread Fusarium-based type B mycotoxin, deoxynivalenol (DON), previously called vomitoxin. DON is a... 

Fusarium species Trichothecenes Zearalenone Fumonisins Moniliformin... 

Edwards S G, Pirgozliev S R, Hare M C and Jenkinson P (2001), Quantification of trichothecene-producing Fusarium species in harvested grain by competitive PCR to determine efficacies of fungicides against Fusarium head blight of winter wheat , Appl. Environ. Microbiol., 67, 1575-1580. 

Miller J D, ApSimon J W, Blackwell B A K Greenhalgh R and Taylor A (2001), Deoxynivalenol a 25 year perspective on a trichothecene of agricultural importance , in Summerell B A, Leslie J F, Backhouse D, Bryden W L and Burgess L W, Fusarium Paul E. Nelson Memorial Symposium, The American Phytopathological Society Press, St. Paul, Minnesota, 310-320. 

Nicholson P, Simpson D R, Wilson A H, Chandler E and Thomsett M (2004), Detection and differentiation of trichothecene enniatin-producing Fusarium species on small-grain cereals , Europ. J. Plant Pathol., 110, 503-514. 

WHO (1990), Selected mycotoxins ochratoxins, trichothecenes, ergot , Environ, Health Criteria 105, Geneva, Switzerland, WHO, 1-163. 

Cundliffe, E., Cannon, M., and Davies, J. (1974). Mechanism of inhibition of eukaryotic protein synthesis b trichothecene fungal toxins. Proc. Natl. Acad. Sci. USA 71, 30-34. 

This material is hazardous through inhalation, skin absorption, penetration through broken skin, ingestion, and produces local skin/eye impacts. Trichothecenes are radiomimetic and may cause bone marrow suppression, liver failure, and internal bleeding. 

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