Trichodiene to 12,13-Epoxytrichothecene and Isotrichodermol

Trichodiene (49), the last hydrocarbon intermediate in the pathway, has been isolated from T. roseum, from Fusarium spp., and also from S. atra (Table 8). Specific labelling experiments have shown it to be a precursor of trichodiol (55) and 12,13-epoxy trichothecene (73), in addition to trichothecolone (101), in T. roseum (277) it is also a precursor of isotrichodiol (53) (219) and 3-acetylvomitoxin (104) in F. culmorum (278). However, relatively little work has been done on this stage of the pathway to simple trichothecenes in Myrothecium, Stachybotrys and Trichoderma spp. 

Much effort, using mainly Fusarium spp., has been devoted to the identification of the oxygenation, cyclisation and esterification steps which take place after the formation of trichodiene. Fermentations carried out on a large scale, or in the presence of enzyme inhibitors, such as ancymidol (225) or xanthotoxin (219), or with mutant strains (223), have yielded metabolic products [(47), (52), (53), (59) Table 8] which are proven intermediates. They are derived from trichodiene by plausible pathways involving allylic hydroxylation at positions 2a and 11a, fol- 

A cell-free enzyme system capable of epoxidizing the 12-ene of a trichodiene derivative has been obtained from F. culmorum (280). This system was also capable of effecting 3a-hydroxylation of the product, an interesting result since 3a-hydroxylation is commonly found amongst the trichothecene relatives. 

There is ample circumstantial evidence that the next step in Fusaria in the pathway to T-2 toxin and 3-acetylvomitoxin after trichodiol/ isotrichodiol is 3a-hydroxylation to trichotriol/isotrichotriol. In feeding studies with a mutant strain of F. sporotrichioides in which this step was blocked, trichotriol, 9-epitrichotriol and isotrichotriol were all converted into T-2 toxin, but trichodiol was not (231), indicating that 3a-hydro-xylation precedes the cyclisation step leading to the trichothecene nucleus. 

Arising from this important conclusion it was suggested (283) that the trichothecenes should be divided into two groups based on the structure of the pathway intermediate immediately preceding cycliza-tion, d-type (e.g. Myrothecium and Trichothecium metabolites) derived from trichodiol and t-type (e.g. most Fusarium metabolites) derived 

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