Tenuazonic acid

Griffin G F and Chu F S (1983), Toxicity of the alternaria metabolites altemariol, altemariolmethyl ether, altemuene, and tenuazonic acid in the chicken embryo assay , Appl. Environ. Microbiol., 46, 1420-1421. 

Euonymus europaeus. Vinca minor Altemaria spp. altersetin, alternariol, alternariol monomethylether, tenuazonic acid 198, 203, 246... 

Janardhanan, K. K., and Hussain, A. (1983). Studies on isolation, purification and identification of tenuazonic acid, a phytotoxin produced by Alternaria alternata (Fr.) Keissler causing leaf blight of Datura innoxia Mill. Mycopathologia 83,135-140. 

In this section, tetramic acids with an acyl group substituent at C-3 are discussed. The simplest of the naturally occurring 3-acyl tetramic acids, tenuazonic acid (6), was first isolated from the culture filtrate of Alter-naria tenuis [18] and, subsequently, from other fungal species (A. alternate, A. longipes, Pyricularia oryzae) [19,20]. Species of Altemaria are known to produce more than 70 secondary metabolites, many of which, particularly those from the Altemaria altemata complex, are mycotoxins [19]. The absolute stereochemistry of 6 (55,65) was deduced from the formation of L-isoleucine on ozonolysis followed by acid hydrolysis [21]. 

The biosynthesis of tenuazonic acid was studied using [l-14C]-labeled acetate. N-acetoacetyl-L-isoleucine (7) was detected by radioactive trapping, indicating that amide formation, rather than carbon-carbon bond formation is probably the first step. None of the simple tetramic acid (8)... 

Tenuazonic acid has a broad toxicity spectrum and is regarded as a mycotoxin [28]. It was first detected as a growth inhibitor of tumour cells (human adenocarcinoma), and was later shown to have weak antibacterial and, at high dose levels (100-500 p,g/ml), antiviral activity towards poliovirus MEF-1, enterovirus (ECHO-9), respiratory viruses (parainfluenza-3), vaccinia and Herpes simplex (HF). It has been shown to be an inhibitor of peptide bond formation in preventing substrate binding to acceptor site of peptidyltransferase in human ribosomes [29]. 

Ancorinosides A-D inhibited MTl-MMP, with median inhibitory concentrations of 440, 500, 370, and 180 p,g/mL respectively, and are an order of magnitude less potent than the known synthetic MMP inhibitor FN-439 (130)] 151,152]. A limited SAR study of the natural products and the aglycon of ancorinoside B indicated that it is the tetramic acid moiety that is responsible for the inhibitory activity of the ancorinosides. Indeed, tenuazonic acid (131), a natural product isolated from the fungus Altemaria tenuis [153] that has the tetramic acid unit as its only functionality, exhibited inhibitory activity against MTl-MMP and MMP2 comparable to FN-439 [151]. 

Tenuazonic Acid. Tenuazonic acid [62] Is a fungal metabolite that has a broad phytotoxicity spectrum (soybean, rice. Datura Innoxia. and lettuce) (235-2371. Toxicity to plants has been attributed to reduced protein synthesis via ribosome Inhibition (211. 21S). 

Altemaria (tenuazonic acid, alternariol) A. altemata apoptosis mutagen onyalai disease... 

Although most of the compounds produced hy Alternaria are generally nontoxic, altemariol monomethyl ether has been shown to be mutagenic in bacteria (Ames tests) [166]. Tenuazonic acid (TA) is a protein synthesis inhibitor and is capable of chelating metal ions and forming nitrosamines. TA is also produced... 

Scott (2001) summarized the available literature on the natural occurrence of Alternaria toxins in fruits. The most frequently detected toxins were alternariol, alternariol methyl ether, and tenuazonic acid in apples, mandarin, melon, and alternariol and its methyl ether in red currant, raspberry, strawberry, gooseberry, and blackberry. Stinson et al. (1980) were able to detect Alternaria toxins after the authors isolated Alternaria strains from blueberries, broke the skin, and inoculated the berries after steam disinfection. In contrast, Tournas and Stack (2001) did not detect Alternaria toxins after infection of blueberries with A. alternata. As discussed earlier in this chapter, fruits become more susceptible to mold invasion during ripening, and this may be a crucial point for inoculation experiments. 

Tenuazonic acid Alternaria spp. Infected cotton plants... 

Tenuazonic Acid.— Tenuazonic acid (208) is generated in the fungus Alternaria tenuis from L-isoleucine and acetate. Recent experiments show that butyric acid is a specific precursor it is presumably implicated via acetoacetic acid. The likely mode of linking of acetoacetate and L-isoleucine was indicated by the isolation of (211) from the cultures. 

In experiments analogous to those discussed for dolichotheline above, A. tenuis was found to be able to substitute added L-valine and L-leucine for l-isoleucine and elaborate the tenuazonic acid analogues (209) and (210) respectively. 

Tenuazonic Acid Azetidine-2-carboxylic Acid P-Lactam Antibiotics... 

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