Non-Macrocyclic Trichothecenes

In 1911, Raphael et al. published the total synthesis of racemic trichodermin (375), which was the first synthesis of a member of the trichothecene family (379). Trichodermin (375) was isolated initially by Vangedal et al. from the culture fluid of a strain of Trichoderma viride in 1965 320). 

After having 394 in hand, Raphael et al. had planned to oxidize the alcohol to a ketone function however, this molecule did not undergo an intramolecular aldol condensation. For this reason, it was necessary to oxidize the alcohol 394 in two steps to keto acid 395, which was then converted into the enol lactone 396. 

In 1960, Brian et al. isolated anguidine (376) for the first time from Fusarium equiseti 

Sporol (377) is a further non-macrocyclic trichothecene, which was isolated in 1986 by Tempesta et al. from Fusarium sporotrichioides (324). The structure first thought to be sporol (377) was proven to be neosporol and a structural revision 

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Grove JF (1996) Non-macrocyclic trichothecenes, part 2. Prog Chem Org Nat Prod 69, 1-70. 

This review lists the trichothecenes recorded in the literature up to Dec. 2000, together with their sources, coupled with a summary of the pathways involved in trichothecene biosynthesis, an area in which significant advances have been made during the past decade. The review contains both macrocyclic trichothecenes ( macrocycles ), previously recorded to Dec. 1991 (7), and non-macrocyclic trichothecenes, previously recorded to Dec. 1995 (2, 3). Some omissions from these earlier lists have been included, and some errors corrected. 

A total of 217 trichothecenes, based on the sesquiterpene skeleton (1) named trichothecane (4), which replaced the earlier (5) scirpane nomen-clature have now been reported from natural sources. They are made up of 133 (61%) non-macrocyclic and 84 (39%) macrocyclic compounds. Thus, 20 new non-macrocyclic trichothecenes have been isolated since 1995 and 17 new macrocycles since 1991. 

Also included in the 133 non-macrocyclic trichothecenes are one uncharacterised compound, seven compounds detected only in the mass... 

For tabulation, the non-macrocyclic trichothecenes have been subdivided into 12,13-epoxytrichothec-9-enes (103, 77%) (Table 1), 12,13-epoxytrichothec-9-en-8-ones (23, 17%) (Table 2), trichothec-9,12-dienes (5, 4%) (Table 3), and miscellaneous (2) (Table 4). Thus, all but five of the non-macrocyclic trichothecenes have the 12,13-epoxide group. The pair of diastereoisomers in Table 4 have a 9,10-epoxide and are the only non-macrocyclic compounds not to have the 9(10)-ene implicit in the name trichothecene. 

Two non-macrocyclic trichothecenes, 8-deoxotrichothecinol A(Table 1 C19H26O5), from Holarrhena floribunda, and miotoxin G (Table 1 C29H40O9), from Baccharis coridifolia, are plant products (but see Notes to Tables 1-4). 

To date, only a few total syntheses of trichothecenes have been published, such as the non-macrocycHc trichothecenes trichodermin (375), anguidine (376), and sporol (377). Examples of the synthesis of macrocyclic trichothecenes are for roridin E (378), baccharin B5 (379), and vemicarin A (380) (Fig. 8.4). 

The first report dealing with the synthesis of a macrocyclic tri-chothecene, albeit a non-natural product, originated from Tamm s laboratory in 1978 (22). Three years later, Still and Ohmizu synthesized the first naturally occurring macrocyclic trichothecene verrucarin A (37) (133). Since 1981, the increased availability of verrucarol (82) (150), the sesquiter-penoid backbone for most of the macrocycles, has stimulated work in this area and culminated in Still s recent syntheses (135) of baccharin B5 (59) and roridin E (47), the most complex trichothecenes synthesized to date. Sandwiched between these landmark syntheses have been equally exciting studies initiated by Tamm (verrucarin A and 3a-hydroxyverrucarin A (106), Fraser-Reid and Jarvis (verrucarin J) (42) and Roush (verrucarin J and... 

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