Trichothecenes structures

Moon, Y., Uzarski, R., Pestka, J.J. (2003). Relationship of trichothecene structure to COX-2 induction in the macrophage selective action of type B (8-keto) trichothecenes. J. Toxicol. Environ. Health A 66 1967-83. 

Mohr P, Tamm Ch, Zurcher W, Zehnder M (1984) Sambucinol and Sambucoin, Two New Metabolites of Fusarium sambucinum Possessing Modified Trichothecene Structures. Helv Chim Acta 67 406... 

Very recently 105a) sambucinol and sambucoin, two compounds possessing a modified trichothecene structure have been described. 

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. 

The isoprenoids contribute most to the list of structural similarities in the sea and on land. They range from common classes in both ecosystems, such as drimane sesquiterpenes, to rare classes in the sea, such as the trichothecenes (Chart 8.3.11). The similarity in marine and terrestrial polyether triterpenes (Chart 8.3.12) may be seen as convergence toward chemically favored structures, starting from squalene as a biosynthetic precursor. Similar conclusions may apply to polycyclic triterpenes. 

Some natural products, or their degradation products, represent a hazard for mammals not because of general toxicity but for subtle, adverse properties, such as carcinogenicity and tumor promotion. They are best known fi om marine dinoflagellates (okadaic acid and structural analogues), filamentous fungi (trichothecenes and ochratoxins), and plants (pyrrolizidine alkaloids). 

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. 

The trichothecenes, a group of sesquiterpenes having a reasonably complex tricyclic structure, represent useful targets for the synthetic application of cyclohexadienyliron complexes. Several members of... 

Trichothecenes are composed of 40 or more structurally related compounds produced by a variety of molds, including Cephalosporium, Fusarium, Myrothecium, and Trichoderma, which grow predominantly on grains. Much of the available information on human toxicity of trichothecenes was obtained from an outbreak of poisoning in Siberia in 1944, mentioned above. 

U. Berger, M. Oehme and F. Kuhn, Quantitative determination and structure elucidation of type A-and B-trichothecenes by HPLC/ion trap multiple mass spectrometry, 7. Agric. Fd. Chem., 47, 4240-4245 (1999). 

Figure 28 Structures of Fusarium trichothecenes (including trichothecene intermediates isolated as natural products). The side chains (e.g., hydroxyl, acetyl, keto) are added to the trichothecene skeleton at C-3 (FT), C-4 (R2), C-15 (R3), C-7 (R4), and C-8 (R5), which are shaded in colors. While type A trichothecene has a single bond at C-8, type B trichothecene has a keto at C-8. Three rings that constitute the trichothecene skeleton [EPT R1 = (1), R2 = (1), R3 = (1), R4 = (1), R5 = (1)] are labeled A, B, and C in bold. It should be noted that EPT is not a Fusarium trichothecene.

Fig. 9. Chemical structures of different trichothecenes. MC = Macrocyclic ISV = isovalerate OH-ISV = hydroxyisovalerate.

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. 

Competition between an alkene and an ether oxygen for participation in epoxide opening is evident in the reactions of trichothecenes (illustrated by the skeletal structure 20 equation 8). In aqueous acid, participation of the ether oxygen is favored and (21) is formed, probably due to preferred cleavage at the tertiary center under the more electrophilic conditions. Under neutral or basic conditions, the diminished role of intermolecular electrophile (water) results in unusual scission of the primary epoxide bond, with formation of (22). ... 

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