Sesquiterpenoids trichothecenes

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. 

Approaches to the simple sesquiterpenoid trichothecenes can be categorized by the type of reaction used to form the ring system. Primarily, four bond associations have been used to construct the trichothecene skeleton as depicted in Scheme 1. Groups 1 and 2 (X = O, Y or Z = OH)... 

Trichothecenes are a numerous group of sesquiterpenoids produced by various species of Fusar-ium, Myrothecium, Trichoderma, Cephalosporium, and other fungi. 

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]. 

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. 

Epoxytrichothec-9-ene (138) (cf. Vol, 4, p. 90), a metabolite of T. roseum and a proposed intermediate in the biosynthesis of trichothecene sesquiterpenoids cf. Chapter 6), has recently been synthesized (Scheme 16). The final cyclization step [(136) (137)] in the synthesis is identical to that proposed in the biosynthesis... 

The trichothecenes make up a family of closely related chemical compounds called sesquiterpenoids (Figure 34-1). The structures of close to 150 derivatives of the trichothecenes are described in the scientific literature.35,43 The specific side structures of the most abundant of the naturally occurring trichothecenes are shown in Table 34-1. Because of its availability and relatively high toxicity, T-2 toxin has been the most extensively studied trichothecene mycotoxin. 

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). 

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