Macrocyclic trichothecene mycotoxins

Islam, Z., Amuzie, C.J., Harkema, J.R., Pestka, J.J. (2007). Neurotoxicity and inflammation in the nasal airways of mice exposed to the macrocyclic trichothecene mycotoxin roridin A kinetics and potentiation by bacterial lipopolysaccharide coexposure. Toxicol. Sci. 98 526-41. 

Jarvis BB, Wells KM, Lee Y-W, Bean GA, Kommedahl T, Barros CS, Barros SS (1987) Macrocyclic Trichothecene Mycotoxins in Brazilian Species of Baccharis. Phytopathol 77 980... 

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. 

Mycotoxins may include butanol, estrogenic compounds (e.g., zearalenone), heptanone, lactones, lactams (patulin), stachybotrylactones, stachybotry-lactams, 2-pentylfuran, 2-hexanone, 2-methyl-1-propanol, 3-methylfuran, 2-methylisoborneol, 3-methyl-2-butanol, and macrocyclic trichothecenes (Satratoxins F, G. and H, Roridine, Verrucarinj, and Trichoverrols). 

R Macrocyclic ester or ester-ether bridge between carbons 4 and 15. The most abundant macrocyclic trichothecenes are verrucarins, roridins, and satratoxin H. Source for this statement Jarvis BB. Macrocyclic trichothecenes. In Sharma RP, Salunkhe DK, eds. Mycotoxins and Phytoalexins. Boca Raton, Fla CRC Press 1991 361-421. 

Data sources (1) Ueno Y. Trichothecene mycotoxins Mycology, chemistry, and toxicology. Adv Nut Res. 1989 3 301-353. (2) Wannemacher RW Jr, Bunner DL, Neufeld HA. Toxicity of trichothecenes and other related mycotoxins in laboratory animals. In Smith JE, Henderson RS, eds. Mycotoxins and Animal Foods. Boca Raton, Fla CRC Press 1991 499-552. (3) Sharma RP, Kim Y-W. Trichothecenes. In Sharma RP, Salunkhe DK, eds. Mycotoxins and Phytoalexins. Boca Raton, Fla CRC Press 1991 339-359. (4) Jarvis BB. Macrocyclic trichothecenes. In Sharma RP, Salunkhe DK, eds. Mycotoxins and Phytoalexins. Boca Raton, Fla CRC Press 1991 361-421. 

Jarvis BB. Macrocyclic trichothecenes. In Sharma RP, Salunkhe DK, eds. Mycotoxins and Phytoalexins. Boca Raton, Fla CRC Press 1991 361-421. 

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). 

Several species of Fusarium infect com, wheat, barley, and rice. Under favorable conditions they elaborate a number of different types of tetracyclic sesquiterpenoid mycotoxins that are composed of the epoxytrichothecene skeleton and an olefinic bond with different side chain substitutions (fig. 9). Based on the presence of a macrocyclic ester or ester-ether bridge between C-4 and C-15, trichothecenes are generally classified as macrocyclic (type C) or nonmacrocyclic (types A and B) (table 5). Other fungal genera producing trichothecenes are Myrothecium, Trichoderma, Trichothecium, Acremonium, Verticimonosporium and Stachybotrys. The term trichothecenes is derived from trichothecin, the first compound isolated in this group [115, 147-153]. 

A potentially important application area for capillary SFC and SFC-MS is in the analysis of thermally labile molecules not readily amenable to gas chromatography, such as mycotoxins of the trichothecene group (48,49). Figure 14 shows a fast separation of four trichothecenes on a short 0.8 m x 25 pm column at 100 C with supercritical CO2 as the mobile phase. Diacetoxyscirpenol (DAS) and T-2 toxin are easily resolved while the two macrocyclic compounds, roridin A and verricarin J, are not well separated. However, even this level of separation is often sufficient given a highly selective detector such as the mass spectrometer. Application of SFC-MS to these compounds is described in detail elsewhere ( ). 

Recognised may be two additional trichothecene types. The type E trichothecenes include mycotoxins with an opened macrocyclic ring and the type F trichothecenes do not have the 12,13 epoxide ring as it is replaced by a vinyl linkage with the oxygen atom in the epoxide ring removed. 

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