Gliotoxin compound

Six-membered rings containing three or more heteroatoms do not occur widely in Nature. The 1,2,4-dithiazine ring occurs in the epidithiodioxopiperazine system (257), which is common to a number of fungal metabolites, such as gliotoxin (258), and appears to be the site of the potent antiviral, antibacterial and antifungal activities of these compounds. However, the compounds are probably better considered as diketopiperazines rather than... 

Organic Syntheses and Organic Reactions, Jack and his students published research papers on organo-boron compounds, furan derivatives, dienes, ketene derivatives, the structure of gliotoxin, and biosynthesis of isoprene derivatives. 

Numerous attributes make G, virens an ideal fungus for mycoherbicide formulations. It is readily cultured, grows rapidly and is long-lived in dried preparations. A unique feature of G. virens is the production of chemical compounds in addition to the phytotoxin viridiol. The two main compounds are the epipolythiodiketopiperazines gliotoxin and gliovirin (15,16). 

Bisdethiobis(methylthio)gliotoxin 592 was heated in dioxane at 70°C for 2 hr in the presence of DBU, to afford a mixture of compounds 593-595 (86CPB340). Under similar conditions pyrazino[l,2-o]indole-l,4(2f/,3//)-dione 597 was obtained from gliotoxin 596. 

Several naturally occurring organosulfur compounds show pesticidal activity examples include nereistoxin (77), isolated from the marine worm Lumbriconereis heteropoda, which is insecticidal, and the antifungal antibiotic gliotoxin (78) (Figure 10), produced by the soil fungus Trichoderma viride. 

Gliotoxin (6) is present in the metabolites of many fungi, such as Trichoderma viride, Gliocladium flbriatum, Aspergillus fumigatus an several Penicillium spp. (Brian and Hemming, 1946). It is a fairly stable compound of composition, 2,3,5a,6-tetrahydro-6-hydroxy-3-hydroxymethyl-2-methyI- lOH-3,1 Oa-epidithiopyrazino-[l,2-a]-indoI-l,4-dion (Bell et al., 1958). 

The reduced form (that is, the dithiol form) of gliotoxin and acetylgliotoxin inhibited partially purified human FPTase with IC50 values of 1.1 and 4.4 /tM, respectively. The oxidized form (that is, the disulfide form) or dimethylthioethers of either of the two compounds did not significantly inhibit FPTase activity. Mechanistically, these compounds were noncompetitive with respect to Ras with a Kj value of 1.5 [134]. 

Reactions of polyunsaturated compounds, which can be formally related to dihydrooxepines, i.e. oxepinones, oxepindiones, and oxepin oxides, are noteworthy. The addition reactions of N-nucleophiles to both benzene oxide and symmetrical oxepin oxide were studied as models for the biogenesis of some natural epidithiadioxopiperazines of gliotoxin and aranotoxin families (Equation (3)) <82JOC1509>. 

In addition to the La., there are many natural indole compounds which are not alkaloids, e.g. the mel-anins, betalaines, sporidesmins and gliotoxin. 

Details of the synthesis of gliotoxin (90) and related compounds have been reported by Kishi and his co-workers. ... 

Gliotoxin (112) was the first member of a series of microbial metabolites containing the unusual disulphide bridged diketo-piperazine ring system to be isolated and characterised . More recently additional members of this class of compound such as arantoin (113) , verticillin A (114) and the closely related chaetocin (115) , and the various sporidesmins (e.g. 116) have been found. Biogenetic considerations have lent considerable assistance to their structural formulation and comparative CD... 

Trown, P. W., Billelo, T. A. Mechanism of action of Gliotoxin, Elimination of activity by sulfhydryl compounds. Antimicrobial Agents and Chemotherapy (in press 1972). 

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