Trichothecene derivatives

Many trichothecene derivatives have been tested as potential anticancer agents but have proved too toxic for clinical use. 

The instrument was operated in the selected ion monitoring (SIM) mode. This allowed groups of one to four ions to be monitored at a time. Masses to be monitored were changed prior to the retention time of each trichothecene derivative. 

One of the advantages of this GC/MS method of detection of the derivatized trichothecenes is the reduction of the effect of the interferences from the sample matrix. Many interferences are small molecular weight compounds, but the large molecular weight trichothecene derivatives can be selectively monitored at the higher mass ions. Interferences seen in the electron capture chromatographic determination of trichothecenes due to the excess HFBI left in the extract after derivatization and due to the low molecular weight compounds from the sample matrix are not apparent in NCI mass spectrometry. 

Negative ion chemical ionization mass spectrometry can be used to confirm trichothecenes and quantitate DON in naturally contaminated grains and feeds. The effects of interferences are eliminated by selectively scanning the relatively high molecular weight fragments and molecular ion of the trichothecene derivatives. Separation of a mixture of trichothecene derivatives is accomplished in 15 minutes on a packed GC column. 

Ghosal G, Chakrabarti DK, Chaudhary KCB (1976) Toxic Substances Produced by Fusarium I Trichothecene Derivatives from Two Strains of Fusarium oxysporum f. sp. carthami. J Pharm Sci 65 160... 

Breitenstein W, Tamm Ch (1977) Verrucarins and Roridins, Part 34. Verrucarin K, the First Natural Trichothecene Derivative Lacking the 12,13-Epoxy Group. Helv Chim Acta 60 1522... 

There exist just a few total syntheses of macrocyclic trichothecenes. However, all of these deal with the synthesis of verrucarol (454), a hydrolysis product of the naturally occurring verrucarin A (380). Venucarol (454) represents the sesquiterpenoid moiety of most macrocyclic trichothecene derivatives. To date, there are several syntheses of this moiety. In 1998, the most recent total synthesis was published by Tadano et al. (327). 

People working with animal feeds may become ill by inhalation or contact with toxic metabolites more usually associated with mycotoxicoses in animals. Thus Stachybotrys alternans and Dendrodochium toxicum, also known as Myrothecium roridum, grow on hay and straw under certain conditions and have caused serious diseases of horses in parts of Russia. These fungi also produce complex trichothecene derivatives, and materials contaminated by them may be dangerous to people handling them. 

The systematic investigation of biologically active substances produced by molds has led during the last few years to the discovery of a number of new trichothecene derivatives. The structures of these compounds are summarized in Figs. 3-8. 

Fig. 3. Structural types of naturally occurring trichothecene derivatives. 1.

Very recently, the isolation and structure elucidation of baccharin (47), an antileukemic trichothecene triepoxide, from Baccharis megapotamica Spreng (Asteraceae) was reported (Kupchan et al, 1976). This constitutes the first known case of a trichothecene derivative in higher plants. The full structure and stereochemistry of baccharin (47) were established by X-ray analysis. 

The first naturally occurring trichothecene derivative without the 12,13-epoxy group has recently been isolated from a strain of M. verrucaria (Breitenstein and Tamm, 1977). The structure of this compound, named verrucarin K (46), is shown in Fig. 8. 

The intermediacy of trichodiol (67) in the biosynthetic scheme has not yet been established conclusively. As stated by Machida and Nozoe (1972b), trichodiol (67) might be a metabolite of 12,13-epoxytrichothec-9-ene (5). In this connection, the recent isolation of verrucarin K (46) (Breitenstein and Tamm, 1977) is noteworthy. As stated earlier, this compound is the first naturally occurring trichothecene derivative lacking the 12,13-epoxy group. In view of this isolation, an alternative pathway may be postulated consisting of the direct cyclization of an intermediate of type 69 to the trichotheca-9,12-diene system 70 (Fig. 13). 

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