Trichoverroids

New trichoverroids from Myrothecium verrucaria Isolated by high speed countercurrent chromatography. J. JVfl/ Prod. 55,1441-1446. 

The trichoverroids and fungal macrocycles are products of Myrothecium and Stachybotrys spp., and one species each of Acremonium, Ceratopycnidium, Cercophora, Cylindrocarpon, Phoma, Phomopsis, and Verticinimonosporium. Acremonium, Ceratopycnidium, Cercophora and Phoma are new sources reported since 1991. 

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. 

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. 

Jarvis BB, Vrudhula VM, Midiwo JO, Mazzola EP (1983) New Trichoverroids from Myrothecium verrucaria Verrol and 12,13-Deoxytrichodermadiene. J Org Chem 48 2576... 

Jarvis BB, DeSilva T, McAlpine JB, Swanson SJ, Whittem DN (1992) New Trichoverroids from Myrothecium verrucaria Isolated by High Speed Countercurrent Chromatography. J Nat Prod 55 1441... 

Jarvis BB, Wang S, Ammon HL (1996) Trichoverroid Stereoisomers. J Nat Prod 59 ... 

The last group of trichothecenes are the trichoverroids which appear in Table VIII. These seco macrocyclic trichothecenes have either partial or complete carbon chains at C-4 and C-15 characteristic of the macrocyclic compounds, but lack the requisite ring-forming bond. The first of these, trichodermadiene (72), was reported by Jarvis and co-workers in 1980 (77). In this compound a diene fragment is affixed to C-4 in a manner reminiscent of the macrocycles, but the C-15 hydroxyl group remains unesterified. Subsequently, Jarvis 78, 83, 86) discovered other such seco compounds which possess the complete carbon chains of the macrocyclic trichothecenes. Evidence has been presented suggesting that the trichoverroids are intermediates in the biosynthesis of the macrocycles 78). 

The isolation of trichodermadiene (72) marked the discovery of the newest class of trichothecene metabolites, the trichoverroids. As noted previously, these are derivatives of the simple sesquiterpenes which possess complex ester side chains, structurally related to those found in the macrocyclic trichothecenes, at C-4 or both C-4 and C-15 (see Table VIII). Evidence for their role as biosynthetic intermediates to the macrocyclic trichothecenes 42, 78) has spurred interest in their synthesis. 

Initially, the most demanding challenge for the synthetic chemist was assigning both the relative and absolute stereochemistry at C-6 and C-T (see Scheme 23) of the ester sidechain. This was first accomplished by Tulshian and Fraser-Reid 149) in 1981. Their methodology was used later to synthesize trichoverrin B (71), the first trichoverroid to be obtained by total synthesis 42). Roush and Spada reported an alternative synthesis of the chiral trichoverroid side chains 118) and have most recently completed a synthesis of trichoverrol B (69) 119). 

The synthetic work on both the trichoverroids and the macrocyclic trichothecenes demands a good source of the sesquiterpene verrucarol (82). At first, this presented a problem as the main source of verrucarol (82) was the hydrolysis of verrucarin A (37), a macrocyclic trichothecene whose supply was somewhat limited. This problem has been rectified by Tulshian... 

Two total syntheses of verrucarin J (40) have been recorded. The first by Esmond, Fraser-Reid and Jarvis (see Scheme 34) is an extension of their work in the trichoverroid area (see Scheme 24) (42). Roush and Blizzard have published a second synthesis of verrucarin J and have developed routes... 

Figure 1. Molecular Structures of Trichoverroids, Macrocyclic Trichotheienes, and Myrotoxins.

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