Mycotoxins ergotism

There are significant differences between cereal species in their susceptibility to mycotoxin-producing fungi and/or my cotoxin contamination levels. For example, wheat is generally more frequently contaminated with DON than rye (Tanaka et al., 1988 Lepschy et al., 1989 Doll et al., 2002), but rye usually has higher levels of ergot contamination than wheat. 

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

Mycotoxins, selected ochratoxins, trichothecenes, ergot (No. 105,1990) Nephrotoxicity associated with exposure to chemicals, principles and methods for the assessment of (No. 119,1991) Neurotoxicity associated with exposure to chemicals, principles and methods for the assessment of (No. 60,1986) Neurotoxicity risk assessment for human health, principles and approaches (No. 223,2001)... 

WHO. Selected Mycotoxins Ochratoxins, Trichothecenes, Ergot (Environmental Health Criteria 105). Geneva, 1990. 

Mycotoxins of most interest are those found in human food or in the feed of domestic animals. They include the ergot alkaloids produced by Claviceps sp aflatoxins and related compounds produced by Aspergillus sp and the tricothecenes produced by several genera of fungi imperfecti, primarily Fusarium sp. 

The mycotoxins with the greatest potential risk to human and animal health as food and feed contaminants are AFs, trichothecenes, fiimonisins, zearalenone, ochratoxin A, and ergot alkaloids.109 Other mycotoxins such as cyclopiazonic acid, sterigmatocystin, gliotoxin, citrinin, penitrems, patulin, fusarin C, penicillic acid, and PR... 

M. K. Matossian, Poisons of the Past Molds, Epidemics and History, New Haven, Conn., Yale University Press, 1989 Selected mycotoxins, ochratoxins, trichothecenes, ergot . 

Matossian, Poisons of the Past Selected mycotoxins, ochratoxins, trichothecenes, ergot . 

It is difficult to conceive that even poisons can be harnessed as medically-useful drugs, yet this is the case with the ergot alkaloids. These mycotoxins (i.e., toxins produced by molds) were responsible for fatal poisoning of humans and animals (ergotism) throughout the ages after consumption of bread made from grain contaminated with species of... 

International Agency for Research on Cancer 1993. Summaries and evaluations. Ochratoxin A (Group 2B). http //www.inchem.org/documents/iarc/vol56/13-ochra.html October 17, 2004. International, Programme on Chemical, Safety 1990. Selected mycotoxins Ochratoxins, trichothe-cenes, ergot, http //www.inchem.org/documents/ehc/ehc/ehcl05.htm March 5, 2004. 

The amino acid tryptophan is a precursor of several fungal metabolites that affect the central nervous system. We have already met it as a constituent of the ergot alkaloids. Roquefortine (9.25) is a metabolite of Penicillium roqueforti and P. camemberti, which are found on some cheeses. Roquefortine is one of a series of mycotoxins that affect the central nervous system and induce tremors. The more complex penitrems are tremorogenic neurotoxins that are produced by the P. crustosum series. They are biosynthesized from a tryptophan and a triterpene unit. 

Ergot alkaloids are mycotoxins produced (mainly) by Claviceps species which have deleterious effects on the central nervous system of mammalia on the other hand, they have a long biotechnological tradition with manifold applications in therapy of human central nervous system (CNS) disorders (for reviews, see Keller and Tudzynski, 2001 Tudzynski et al., 2001). Chemically they are 3,4-substituted indole derivatives having a tetracyclic ergoline ring structure (Fig. 2). 

Examples of mycotoxins include the ergot alkaloids produced when the ergot fungus grows on rye (responsible for outbreaks of a disease called ergotism, or St Anthony s Fire), trichothecanes produced by Fusarium species (associated with alimentary toxic aleukia fatalities in the Second World War) and the aflatoxins. 

In the 1980s Muratake and Natsume (202) in a number of reports presented a new, interesting approach to the synthesis of substituted indole derivatives that focused on their use as intermediates in the preparation of a variety of clavine alkaloids and mycotoxins. The method elaborated by the authors consisted of constructing the specifically substituted benzene portion of the indole nucleus, with 1-methoxycarbonylpyrrole being the starting material. The functionalized 4-alkylindole thus obtained was transformed to a tricyclic indole derivative which appeared to be a common intermediate for the synthesis of several ergot alkaloids, as exemplified by the synthesis of ( )-dihydrosetoclavine (203-205) (Scheme 42). Recently, the application of this method was extended by the authors (206) to the syntheses of a series of marine alkaloids, the hapalindoles. Most of these alkaloids have a tetracyclic framework made up of 3,4-substituted tryptamine and two isoprene units. 

Similar structural features are also demonstrated by penitrems A to F (Fig. 18), which form a small family of tremorgenic mycotoxins produced by the ergot fungus Penicillium crustosum. The structure of these alkaloids was elucidated by Steyn and co-workers (238-241), and an approach to the total synthesis of penitrem D was also presented (242). 

Penitrem D (226) (Scheme 41) is one member of the penitrem family, which is a small family of structurally complex tremorgenic mycotoxins, and was isolated from the ergot fungus Penicillium crustosum by Steyn and coworkers in 1981 [90]. 

---