Trichothecene complex

The trichothecenes, a group of sesquiterpenes having a reasonably complex tricyclic structure, represent useful targets for the synthetic application of cyclohexadienyliron complexes. Several members of... 

The direct coupling of the tin enolate (175 Scheme 25) with (30) gives complex (176) in good yield (87%). Fortuitously, the bond formation gives approximately a 5 1 mixture in favor of the diastereomer required for trichothecene synthesis. Further elaboration of the major isomer leads to (i)-trichodiene (167), representing an eight step diastereoselective total synthesis of the natural product from p-methyl-anisole, which compares very favorably with previous methods.32-36... 

Kalinoski et al. [32] has applied this method to the determination of tri-chothecene mycotoxins in wheat. The methods were based on chemical ionisation MS and collision-induced dissociation tandem MS and enabled the rapid identification of ppm levels of several trichothecene mycotoxins. Supercritical carbon dioxide is shown to allow identification of mycotoxins with minimum sample handling in complex natural matrices such as wheat. Tandem MS techniques are employed for unambiguous identification of compounds of varying polarity, and false positives from isobaric compounds are avoided. Capillary column SCFC-MS of a SCF extract of the same sample was also performed, and detection limits in the ppb range appear feasible. 

The trichothecene framework 114 was constructed by interesting Pd-catalysed skeletal reorganization via pinacolone rearrangement of the allylic lactone 111. The exo-7r-allylpalladium complex 112 is attacked intramolecularly by a carbon bond (pinacolone rearrangement) to give 113 [60]. 

The following application of the synthetic equivalent 110 was carried out. Complex 107 was utilized for the total syntheses of trichothecene (122), trichodiene and trichodermol, applying the reaction of cationic complex 107 with a /f-kcto ester or tin enolate [28]. The tin enolate of cyclopentanone 119 reacted with the complex 107 with high diastereoselectivity to give the diene complex 120 in high yield. After... 

Recently, few topics in analytical chemistry have occupied the scientific community more than the ability of chemical laboratories to reliably determine at the low parts-per-billion level the presence of Fusarium trichothecenes in environmental and toxicological samples. This paper provides a systematic approach for developing and implementing a quality assurance and quality control program for a complex analytical method in which human error and system failure can occur. The application of this approach to the problem of determining the presence of nine naturally... 

McCormick SP, Stanley AM, Stover AN, Alexander NJ (2011) Trichothecenes From Simple to Complex Mycotoxins. Toxins 3 802... 

Melchert, H.-U. Pabel, E (2004). Reliable identification and quantification of trichothecenes and other mycotoxins by electron impact and chemical ionization-gas chromatography-mass spectrometry, using an ion-trap system in the multiple mass spectrometry mode. Candidate reference method for complex matrices. Journal of Chromatography A, Vol. 1056, No. 1-2, (November 2004), 195-199, ISSN 0021-9673. 

There are a large number of different trichothecenes and ideally their analysis requires confirmation using GC-MS and analysis of the macrocyclic trichothecenes, which includes the verrucarins, ror-idins, and satratoxins, requires considerable experience and a specialized laboratory. However, well-established methods are available for individual trichothecenes of particular importance, such as T-2 toxin, diacetoxyscirpenol, deoxynivalenol, and neosolaniol. The large niunber of Fusarium trichothecenes are acylated derivatives of a much smaller niunber of parent alcohols, such as T-2 tetraol, scirpentriol, deoxynivalenol, and nivalenol, so another approach to their analysis is to hydrolyze the possibly complex mixture of trichothecenes to the parent alcohols and analyze these as their trimethylsilyl ethers. However, when this is done, there is often a poor correlation between total trichothecene content and observed toxicity, reflecting the large differences in the toxicity of different acyl derivatives even of the same parent alcohol. 

Two trichothecene mycotoxins (nivalenol and deoxynivalenol) and two related esters (3-acetyl- and 15-0-acetyl-4-deoxynivalenol) were extracted from wheat flour and separated on a Cjg coluitm (2 = 220nm). A complex 36-min 92/8 - 0/100 (9/10 water/acetonitrile)/acetonitrile gradient gave good resolution and peak shape [1100]. Standards containing 3 ppm of each compound were easily detected. 

As mentioned in the Introduction, the group 3 biomimetic approach (see Scheme 1) has been the most popular route to the trichothecene skeleton. Two different moieties have served as the electrophilic site for biomimetic cyclization. When the cyclization proceeds via an allylic carbonium ion (127) (Path A, Scheme 9), the desired trisubstituted olefin (126) is obtained directly. On the other hand, the Michael acceptor (128) (PathB) yields, upon cyclization, a ketone (129) which must then be transformed into the olefin (126), a process which shows good but not complete regioselectivity. Hence, Path A, which can also be entered from the enone (128), is the superior route. Further analysis of Scheme 9 reveals that the primary stereochemical challenge of the biomimetic approach is to control the relative stereochemistry at the two quaternary centers C-5 and C-6. Within the context of trichothecene synthesis, a number of useful protocols have been devised for this purpose and include photocyclization (99), selective ring contraction (134), Diels-Alder cycloaddition (117,125) conjugate addition (27,120), and interconversion of dienyl iron complexes (114). 

Koreeda and Luengo have reported the most reeent of these miscellaneous approaches which resulted in the first synthesis of the 6,11-diepitrichothecene skeleton (89). Their sequence, shown in Scheme 22, is based on an intramolecular version of the Diels-Alder reaction. Preparation of the two dienol ethers (210) and (211) was carried out from the common intermediate (209). While heating the -isomer (210) produced no cyclized materials, the Z-isomer, upon heating, produced the 6,11-diepitri-chothecene (212) in an 80% yield. It should be recalled that this trichothecene isomer could not be prepared via a group 3 type cyclization (see Scheme 14). Obviously, the extension of this approach to more complex trichothecene skeletons remains to be explored. 

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. 

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... 

People working with animal feeds may become ill by inhalation or contact with toxic metabolites more usually associated with mycotoxicoses in animals. Thus Stachybotrys alternans and Dendrodochium toxicum, also known as Myrothecium roridum, grow on hay and straw under certain conditions and have caused serious diseases of horses in parts of Russia. These fungi also produce complex trichothecene derivatives, and materials contaminated by them may be dangerous to people handling them. 

Two types of trichothecenes may be distinguished on the basis of structural characteristics the alcohols and simple esters (Table I, Figs. 3-6), and the more complex macrocyclic di- and triesters (Table II, Figs. 7 and 8). 

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