Trichoverroids and Macrocyclic Trichothecenes

The genes controlling the initial stages of the biosynthetic pathway to the verrucarol moiety of the macrocychc trichothecenes have been studied in Myrothecium roridum (311). In so far as the pathways overlap, the pathway outlined above for simple trichothecenes is followed, and clustered genes MRTri4-6, similar to Tri4-6 and with the same function. 

The sequence of the hydroxylation and esterification steps in Myrothecium spp. fermentations between trichodermol (110) and the C-7 diastereoisomeric trichoverrins (C-6 S) (140) and isotrichoverrins (C-6 R) is unclear and has still to be tested with specifically labelled compounds. The pattern of secondary metabolites which could be intermediates, verrucarol (138), verrol (139), the trichodermadienediols (136) and the trichoverrols (137), again suggests a metabolic grid rather than a unique pathway. 

The six-carbon moiety attached to C-15 in verrol and the trichoverrins is mevalonate-derived 248), and after cyclisation to form the macrolide, the 2 -ene can undergo hydrogenation, a-epoxidation, or hydration. The ethylenic double bonds in the acetate-polymalonate-derived eight-carbon moiety attached to C-4 in the trichoverroids occur as Z or E (see Table 1), but are always 7 (E), 9 (Z) in the macrolide. 

Ring closure of the trichoverrins occurs with inversion of configuration at position 6. In most roridins and all baccharinoids C-6 is R the corresponding centre in the trichoverrins is S. Exceptionally, iso-roridin E, 13 -epiiso-roridin E and 6 -epi-13 -epiroridin A have C-6 S, but the M. verrucaria strains which produce them also produce isotrichoverrins with C-6 R (113). Trichoverrin B has been proved to be a precursor of roridin A (28 R = R = H, R = R = /3H) and verrucarin A (7 R = H, R = OH) (705). 

It is likely that the trichoverroid roridin L-2 (142) and its close relatives arise by hydrolysis and relactonisation of the corresponding, unknown, 12 -hydroxyroridin E analogues. 

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