Roridines

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... 

Figure 1. Structures of roridins and baccharinoids (B1-B20) isolated from B. megapotamica.

Our findings suggest that some Baccharis species form an association with Myrothecium species which produce roridins. These roridins are taken up by the plant and, in the case of B. coridifolia stored, but in the case of B. megapotamTca the roridins are oxidized (metabolized) (45) to the baccharinoids. 

T-2 toxin HT-2 toxin Neosofaniol (NESO) Diacetoxyscirpenof (DAS) T-2 tetraof (T-4of) deoxynivalenol (DON) nivalenof (NIV) fusarenon-X roridins verrucarins stachyhotryotoxins... 

Experimentally, the macrocyclic trichothecenes satra-toxin G, isosatratoxin F, and roridin A have been shown to cause nasal and pulmonary toxicity when administered intranasally or intratracheally to mice. Intranasal exposure of satratoxin G and roridin A induced apoptosis of olfactory sensory neurons resulting in atrophy of the olfactory epithelium and olfactory nerve layer of the olfactory bulb in the frontal brain (Islam et al, 2006, 2007). Alveolar-type II cells and alveolar macrophages were injured following intratracheal instillation of isosatratoxin F or Stachybotrys spores with marked changes in surfactant synthesis and secretion (Rand et al, 2002). 

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. 

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). 

Frequently, organisms will produce several members (factors) within a family of compounds. Product-ion MS/MS spectra can often be used to propose new structures within these series of natural product factors. For example, LC-MS/MS can provide both the molecular weight and product-ion MS/MS spectra of the unknowns. Database searches using these spectra may produce a match to a known natural product in the sample, which can be conlirmed as previously described. In addition, the correlation of product ions and neutral losses from the MS/MS spectra with the structure of these known compounds can often be used to propose structures for the other related factors in the sample. An example of this correlation was shown by Janota et al. [84], who used this approach to propose several structures within the roridin family. 

The roridin family constitutes another subclass of the trichothecane macrolides. Two examples of this group are roridin E (148) and baccharin Bj (150). The latter is isolated from the plant Baccharis megapotamica and is a potent antileukemic agent. Structurally, this class of compounds is quite similar to the verrucarins discussed above, with the exception of the replacement of the hydroxypentanoic acid-muconic ester linkage by an ether bond and some additional carbon substitution. 

The pigments of the Fusaria have been described in Chapter 7. Many of the characteristic phytotoxic metabolites are the sesquiterpenoid trichothecenes (8.38) (see Chapter 5). The more highly hydroxylated members have considerable mammalian toxicity as well as phytotoxicity. Trichothecenes have been identified as metabolites of species from ten of the twelve sections of the genus Fusarium as classified by Booth. The trichothecenes occur with various combinations of oxygen substituents at positions 3, 4, 7, 8 and 15. Several trichothecenes contain macrocyclic esters linking C-4 and C-15. These are known as the roridins and verrucarins. 

Trichothecenes are characteristic metabolites of Fusarium species and have been isolated from species belonging to ten of the twelve sections of the genus Fusarium as classified by Booth. The majority contain a 12,13-epoxide and a C-9 C-10 double bond and occur with various combinations of additional oxygen substituents at positions C-3, C-4, C-7, C-8 and C-15. Many of the hydroxyl groups are esterified and there are several macrocyclic esters known as the verrucarins and roridins in which the esters link C-4 and C-15. 

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