Trichothecane

Tribenzoxepin-3-carboxylic acid, 1-methyl-NMR, 7, 552 Trichosiderin synthesis, 3, 1010 Trichosiderin pigments structure, 3, 1038 Trichothecane, 7, 400 Trichoviridine, 7, 192 Tricromyl... 

A cell-free extract obtained from T. roseum has been shown to convert trans,trans-farnesyl pyrophosphate into trichodiene (87), the bicyclic hydrocarbon precursor of the trichothecane sesquiterpenoids.42 Related studies in this area have also been reported.43,44 Chemical and spectroscopic evidence has been reported which is consistent with the structure assigned to vetisporin (88), a new antibiotic isolated from Verticimonosporium diffractum.45... 

Myrothecium verrucaria and M. roridum,383 but neither [l,8-14C2]-(l jR,6i S)-a-bisabolol nor its (l S)-isomer was incorporated into the verrucarol skeleton,384 thus indicating that bisabolene derivatives are probably not intermediates in the formation of the trichothecane skeleton. The recent report of the occurrence of trichodiol (118) and of (119) has led to speculation385 that direct cyclization of 2-cis-6-trans-farnesol might be involved in the formation of the trichothecane skeleton the conversion of an intermediate such as trichodiene (120) into (118) should involve... 

The trichothecane group of sesquiterpenoids are now well recognized metabolites from such fungal sources as Trichothecium, Myrothecium, and Fusarium. To date the main interest in this group has centred around isolation, structural... 

Trichothecenes from Pusarium, Stachybotrys, and Trichoderma, among others. Note Trichothecenes include sesquiterpenes with a trichothecane skeleton, olefinic groups at C-9 and C-10, and epoxies at C-12 and C-13. Macrocyclic trichothecenes have a carbon chain between C-4 and C-15 in an ester or ether linkage (e.g., T-2 toxin, DON, satratoxins G and H verrucarins B and J, trichoverrins A and B)). 

Rearrangement. An entry into the trichothecane nucleus from a fused ring portion to the bridged ring system is based on ionization of the allylic lactone that triggers a C-C bond migration. The product is a synthetic precursor of verrucarol. 

Full details of the neat synthesis of the ketone (126) and its methylenation to give trichodiene (127) have been published.82 Unfortunately, sixteen attempts with different reagents to carry out a similar methylenation of the diastereoisomeric ketone (128) to give bazzanene (129) failed. A number of new and very interesting trichothecane sesquiterpenoids have been isolated from Myrothecium verrucaria. These include trichodermadienediol A (130), trichoverrol A (131), and trichoverrin A (132) together with their B counterparts which are epimeric at C-7. 83 The trichoverrins are clearly biosynthetic intermediates of the more toxic macrocyclic... 

Pearson and Ong86 have extended their route to trichothecane sesquiterpenoids via organoiron complexes by the synthesis of (144) (Scheme 14). The Diels-Alder approach to the construction of the cw-fused AB ring junction of the tricho-thecanes has been much in evidence. The use of methyl coumalate (145) as a... 

Section 4 deals with the total synthesis of macrolides having more than one lactone linkage in the macrocyclic ring. Compounds included in this group range from the dimeric lactone pyrenophorin and the trichothecanes to the tetrameric lactone nonactin. 

The macrocyclic trichothecane lactonic esters are a biologically important class of compounds produced by various species of the Myrothecium group of microorganisms. This family of substances has exhibited marked biological activity... 

From a structural standpoint, these compounds consist of a trichothecane sesquiterpene diol linked through ester bonds to a diacid derived from esterification of the ( )-acid of a (Z, )-muconic acid with a 5-hydroxypentanoic acid segment (containing various substitution patterns). As the synthesis of the sesquiterpene diol unit is beyond the scope of this chapter, we have limited discussion to the methods employed for formation of the macrocyclic ring of these substances. Papers concerning the construction of the various trichothecane diol systems may be found by consulting the references cited in this section. 

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. 

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. 

Recent independent reports describe the syntheses of compounds (147) and (148), which could serve as intermediates in projected synthetic routes to verrucarol (149), a typical trichothecane sesquiterpenoid. Four mycotoxins... 

Further studies on the biosynthesis of the trichothecane sesquiterpenoids (Vol. 8, p. 74) have shown that the coupling pattern in trichothecin (156) derived from [l,2- C2]acetate is consistent with the previously established route to this compound (cf. Scheme 14) and excludes an alternative folding of the farnesyl pyrophosphate (153) precursor/ The prodigious efforts of the late Professor S. 

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