Trichothecene mycotoxins structure

Trichothecene mycotoxin Toxin produced by fungal molds it inhibits protein synthesis, impairs DNA synthesis, and interferes with cell membrane structure and function. 

Trichothecene mycotoxins are produced by a number of fungal molds of the Fusarium, Myrotecium, Trichoderma, and Stachybotrys genera. They inhibit protein synthesis, impair DNA synthesis, and interfere with cell membrane structures and functions. The potential routes of exposure are inhalation, ingestion, and skin absorption. A terrorist may take advantage of any of these routes. 

FIGURE 26.1. Chemical structure of trichothecene mycotoxins from group A, T-2 toxin group B, deoxynivalenol (DON) and group D (satratoxin H). From Haschek et al. (2002). 

The trichothecene mycotoxins, whose basic skeleton is depicted by structure 12, have attracted considerable attention. Novel structures, including macrocycles linked through C-4 and C-15 (84ZN(C)212), have been elucidated. In our laboratories we have combined the screening abilities of FAB-MS... 

Trichothecene mycotoxins are a group of sesquiterpenoid mycotoxins produced by fungi from the Fusarium family. There are four types Type-B such as nivalenol differs from Type-A such as diacetoxyscirpenol by the presence of the keto-group in the C8 position. Type-C has an additional epoxide group, and Type-D are macrocyclic trichothecenes. Human and animal toxicoses by these toxins have been dne to the consnmption of contaminated grain. The structure of some of the Type-A and Type-B componnds is shown in Table 14.2. 

Many mycotoxins have been reported on the basis of various toxicological experiments. Some have been indicated as etiological agents of certain human and animal mycotoxicoses, such.as trichothecene mycotoxins. Fig. 1 shows the general structure and numbering system of trichothecene mycotoxins. 

The trichothecenes make up a family of closely related chemical compounds called sesquiterpenoids (Figure 34-1). The structures of close to 150 derivatives of the trichothecenes are described in the scientific literature.35,43 The specific side structures of the most abundant of the naturally occurring trichothecenes are shown in Table 34-1. Because of its availability and relatively high toxicity, T-2 toxin has been the most extensively studied trichothecene mycotoxin. 

Trichothecene mycotoxins are secondary metabolites of various fungal species. Structures of some trichothecene mycotoxins of interest to the US ARMY are given in Figure 1. Several methods have been reported for the analysis of these toxins (1-11, 15). Of these, mass spectrometry techniques are both sensitive and definitive when applied to toxicologic and environmental samples. With current technology, the most sensitive and qualitatively definitive analytical technique for the determination of these toxins is derivatization with an electron deficient moiety followed by analysis with negative ion chemical ionization gas chromatography-mass spectrometry (NICI-GC/HS). 

Figure 1. Structure of Some Simple Trichothecene Mycotoxins...

Recently, Bayliss et al. [132] described the synthesis of anthracene-9-carbonyl chloride and its aplications as a label for fluorescence and UV absorbance detection of hydroxy compounds. The preparation and properties of esters of short-chain alcohols, diols, trichothecene mycotoxins and sterols were investigated. Anthracene-9-carbonyl chloride was prepared from commercial anthracene-9-carboxylic acid. Derivatization was carried out in acetonitrile free from water or active hydrogen compounds. The reaction rate was dejjendent on the structure of the alcohol. The derivatization of diethylene glycol was complete at ambient temp>erature within 10 min (0.25 M reagent) or 30 min (0.1 M reagent) without a catalyst, but required 1 h for diolesteroL testosterone and the trichothecene T-2 toxin. For sterically hindered alcohols such as t-butanol and 17a-methyl-testosterone, more than 10 h, or refluxing for 1 h, was needed to complete the reaction. The derivatives had absorption maxima at 250 run. Both normal and reversed phase HPLC were applied to the separation of the derivatives. 

There are more than 170 known trichothecenes which can be classified in four categories (A, B, C, and D) according to their chemical structure (Krska et al., 2001). All trichothecene mycotoxins have a basic tetracydic sesquiterpene structure with a six-membered oxygen containing ring, an epoxide group on the 12,13 position, and an olefinic bond on the 9,10... 

GC/FTIR data have also contributed to the structure elucidation of other compounds of biological origin, such as mycotoxins, which are formed by fungal activity in food products under specific environmental conditions of moisture, temperature, and host. Trichothecene mycotoxins, secondary fungal metabolites produced by species of mold, are a natural contaminant of feedstuffs and food. Because they can be toxic to humans and animals, their detection is important. Sehat et al., utilized GC/MI-FTIR and GC/MS to analyze grains for these contaminants. 

Tamm, Ch., and W. Breitenstein The biosynthesis of trichothecene mycotoxins. In Biosynthesis of Mycotoxins (Steyn, P. S., ed.), p. 69. New York Academic Press. 1980. Tatsuno, T. Chemical synthesis of trichothecenes. Dev. Food Sci. 4, 47 (1983). Tatsuno, T., Y. Fujimoto, and Y. Morita Toxicological research on substances from Fusarium nivale. III. Structure of nivalenol and its monoacetate. Tetrahedron Letters 1969, 2823. 

R. A. Shank, N. A. Foroud, P. Hazendonk, F. Eudes and B. A. Blackwell, Current and Future Experimental Strategies for Structural Analysis of Trichothecene Mycotoxins - A Prospectus, Toxins, 2011, 3,1518. 

Steinmetz WE, Rohustelli P, Edens E, Heineman D. Structure and conformational dynamics of trichothecene mycotoxins. J. Nat. Prod. 2008 71 (4) 589-594. 

TRICHOTHECENE MYCOTOXINS. A family of structurally related poisonous substances produced by various species of fungi, especially Acremorium (Cephalosporium), Fusarium, Myrothe-cium, Stachybotrys, Trichderme, and Verticumonosporium. Tri-chothecene mycotoxins are toxic to humans because they inhibit cellular protein synthesis. Prominent examples are deoxynivalenol (sometimes referred to as vomitoxin because it induces vomiting), diacetoxyscirpenol, HT-2, nivalenol, and T-2. These five toxins gained some notoriety in the so-caUed yellow rain events in Southeast Asia because of allegations that they were associated with Soviet-inspired use of chemical weapons (CW). 

Contamination occurs primarily in wheat, barley, rye, and maize. Type A trichothecenes include mainly T-2 toxin, HT-2, and diacetoxyscirpenol (DAS) mycotoxins of the group B include mainly 4-deoxynivalenol (DON), commonly known as vomitoxin, and nivalenol (NIV). Toxic effects include nausea, vomiting, visual disorder, vertigo, throat irritation, and feed refusal in farm animals. The most toxic is T-2, followed by DAS and NIV, with DON being the least toxic in acute toxicity studies but the most widespread in grains worldwide and therefore the most studied. Issues related to chemical and physical data, occurrence, toxicity, absorption, distribution, and metabolism of trichothecenes are reviewed in WHO (89) and IARC (34). Physicochemical data for some selected Fusarium toxins is given by Sydenham et al. (90). The molecular structures of the main trichothecenes are shown in Fig. 9. 

Trichothecences are a class of structurally similar mycotoxins produced principally by Fusarium molds. These cyclic compounds are of interest to feed manufacturers because they can cause feed refusal or reduced feed efficiencies in some animal species (1,2,3). Several approaches have been reported for the analysis of trichothecenes in feeds and feed ingredients. Trimethylsilyl derivatives of the trichothecenes have been formed and the derivatives measured by gas chromatography using a flame ionization detector (4,3,6,7). Other workers obtained improved... 

Mirocha CJ, Panthre SV, Pawlosky RJ, Hewetson DW. Mass spectra of selected trichothecenes. In Cole RJ, ed. Modern Methods in the Analysis and Structure Elucidation of Mycotoxins. New York, NY Academic Press 1986 353-392. 

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). 

The specificity of monoclonal antibodies make it possible to develop an analytical method for a single mycotoxin, such as aflatoxin Bi in maize and groundnut meal, or aflatoxin Mj in milk and milk products. Even within chemically closely related structures such as the Fusarium trichothecenes there is very little cross-reactivity between a monoclonal raised to a single toxin such as T-2 toxin and other members of the family. Thus, a monoclonal raised against 3-acetyl-deoxynivalenol showed negligible cross-reactivity with deoxynivalenol, nivalenol, or T-2 toxin. 

As made evident in Table 2, immunoassays are also in routine use for analysis of mycotoxins, a group including the most dangerous and analytically elusive food-related toxins. In spite of the small structural differences within specific groups of mycotoxins (aflatoxins, ochratoxins, trichothecenes), assay specificity toward the other mycotoxin groups is always total. Determination of AEBi, toxin T-2, and ochratoxin A in a single extract from barley grains has been reported. Mycotoxins may be determined in crude extracts of various foodstuffs at concentration over 20 ng per kg. This detection limit can... 

Fusarium toxins, also called trichothecenes. Other mycotoxins are also encountered but to a lesser extent, and consecutively they are of less concern for public authorities cyclotropiazonic acid, sterigmatocystin, pe-nitrem A, and tenuazonic acid. The structures of these mycotoxins are shown in Figures 1-10. 

FIGURE 6.4 Chemical structure of most common grain mycotoxins. (a) Zeralenone. (b) Ochratoxin A or OTA. (c) Fumonisin. (d) Trichothecenes or T-2. (e) Deoxynivalenol or DON. (f) Ergotamine. 

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