Toxicity principles

Several species of the moray eel (Gymnothorax) have caused toxic reactions, especially ki Japan. The toxic principle appears to be protekiaceous and is found predominately ki the blood but it may occur ki the flesh as well. Its exact stmcture remains somewhat uncertain. 

Coniine, C H N. is the toxic principle of the poison hemlock drunk by Socrates. When subjected to Hofmann elimination, coniine yields 5-(iV,N-dimethylamino)-l-octene. If coniine is a secondary amine, what is its structure ... 

Ailanthus altissima (tree of heaven) grows in pure stands, hence, secretion of a toxic principle is implied. Mergen (98) prepared aqueous extracts of the foliage and found growth inhibition produced in 45 of 46 species of test plants. 

Algal blooms in fresh water ponds occasionally poison livestock and waterfowl. Axenic cultures of Anabaena flos-aquae NRC 44-1 were shown to produce the toxic principle (5) which can be present in the algae and in the water of mature cultures (6). The discovery of the toxin was fortuitous in the sense that AChR agonists do not have a (known) constructive function in the algae evolution of the synthetic pathway was likely a by-product of metabolic pathways in the algae. The compound became evident only through its toxic effects on other organisms. 

Distribution. The first indication of the occurrence of palytoxin in fish was presented in 1969 (16). The filefish Altera scripta belonging to family Monacathidae was traditionally known in Okinawa, Japan, to contain a toxic substance in the gut and, thus, to kill pigs when fed to them. The presence of fragments of Palythoa sp. in the guts and the resemblance in solubility between the fish toxin and palytoxin led the authors to a conclusion that the toxic principle in the filefish viscera was palytoxin. Incidence of human intoxication due to eating the filefish was not confirm. ... 

From this brief review of marine vertebrate venoms, it is obvious that very few biochemical investigations have been done. The technology to study marine vertebrate venom components is available. There are simply not enough scientists interested enough to enter the field. The first task is to isolate the toxic principles and identify the amino acid sequences. Pharmacological investigation should be done on the purified toxic principle and not on the crude venom, which is a mixture of many proteins and nonproteins. 

Alteromonas species producing sodium channel blockers, 80r,82 Anabaena flos-aquae neurotoxins, 88 toxic principle, 108 Analyses, definition, 43 Anatoxin(s) isolation, 88 types, 88,91 Anatoxin a... 

Extensive metabolic work continues with the pyrrolizidine alkaloids many of which are known toxic principles of plants responsible for conditions such as irreversible hemorrhagic liver necrosis, megalocytosis, and cancer. Considerable interest remains in the metabolism of pyrrolizidine alkaloids and their A-oxides to metabolic pyrroles thought to participate in molecular events associated with the above-mentioned toxicities. The chemistry and pharmacological properties of the pyrrolizidine alkaloids is authoritatively discussed by Wrobel in Volume 26 of this treatise. 

Biological effects of plant proteins on human health have attracted wide attention in the recent past because of the presence of various anti nutrients such as trypsin inhibitors, hemagglutinins, and toxic principles U). Adequate cooking and/or processing inactivates these materials and can improve the quality... 

Di 2 fluoroethyl phosphorofluoridate (XVIII) was prepared with the idea of combining the toxic principles of the fluoro-aoetates and of the phosphorofluoridates. It was readily obtained by the action of phosphorus oxydichlorofluoride on... 

The toxic principle of D. cymosum has been isolated by Marais and proved to be potassium fluoroacetate.2 It is evident that this is indeed the heart poison referred to by Steyn in his vivid account given above. 

Structurally rather complicated target molecules can be synthesized with the aid of thi-olate 1,6-addition reactions to acceptor-substituted dienes as well. For example, a richly functionalized proline derivative with a 2,4-pentadienal side chain was converted into the corresponding 6-phenylthio-3-hexen-2-one derivative by 1,6-addition of phenylthiolate, treatment of the adduct with methyl lithium and oxidation (equation 46)127. The product was transformed into acromelic acid A, the toxic principle of clitocybe acromelalga ichimura. Similarly, the 1,6-addition reaction of cesium triphenylmethylthiolate to methyl 2,4-pentadienoate served for the construction of the disulfide bridge of the macrobicyclic antitumor depsipeptide FR-901,228128. 

Stijve, T. (1981). High performance thin-layer chromatographic determination of the toxic principles of some poisonous mushrooms, Mitt. Geb. Lebensmittelunters. Hyg., 72, 2432-2436. 

A crude toxic principle, which we now know to be only about 0.2% pure, was obtained by Yoshizumi Tahara (9,10) in 1909. He named this tetrodotoxin. In 1950 Aikira Yokoo (11) obtained pure crystalline tetrodotoxin. The purification was further developed by Tsuda and co-workers (12) so that the production of the necessary amounts of tetrodotoxin for structural and chemical studies could be achieved. From 1000 kg (1 ton) of pufferfish ovaries they obtained 8-10 g of tetrodotoxin. 

Another example of the use of the [5-1-2] cycloaddition as a strategy-level reaction is provided in the total synthesis of (-i-)-aphanamol I (138) [41], isolated in 1984 as a minor toxic principle of Aphanamhcis grandifolia. This target presents an array of synthetic challenges that are addressed quite effectively using the allenyl [5-1-2] cycloaddition. In this case, the allenyl unit ultimately functions as a ketene equivalent in the... 

The fruit of a shrub which grows in Sierra Leone is very toxic and has been used as a rat poison. The toxic principle has been identified as Z-18-fluoro-9-octadecenoic acid. Suggest a synthesis for this material from 8-fluorooctanol, l-chloro-7-iodo-heptane, acetylene, and any other necessary organic or inorganic reagents. 

As in the case of propachlor mercapturic acid sulfoxide, the biological significance of xenobiotic mercapturic acids that contain oxidized sulfur is not known. Casida et al. (39) have reported that sulfoxidation of some thiocarbamate herbicides is a beneficial step in the detoxication process. However, cysteine conjugates can exhibit adverse biological activities. Smith (40) has reviewed work on the metabolism of the toxic principle in kale and has shown that C-S lyase action on S-methylcysteine sulfoxide produces the toxic principle. Virtanen ( ) has reviewed the processes in other plants that lead to the production of compounds with biological activity from -substituted cysteine sulfoxides. 

Pinnatoxin A (5) (Figure 7.1) was isolated by Uemura and co-workers in 1995, which is one of the major toxic principles responsible for outbreaks of Pinna... 

Ryania speciosa (Flacourtiaceae) and several related species are unique in that their insecticidal activity was discovered as a part of a search for new insecticides (89). The toxic principle is a diterpene esterified to pyrrole-2-carboxylic acid. This insecticide proved to be somewhat selective in its activity (89). 

Few of these have been found so far, the first not until 1944, in a poisonous South African plant, Gifblaar . The toxic principle of this was identified44 as fluoroacetic acid. A recent summary45 indicates that some 10 fluorinated natural products have now been isolated (in small amounts) largely from other plant sources, their formation being rationalized from the metabolism of fluoroacetate. The exception is nucleocidin (1), an antibiotic from a microbial source (Streptomyces calvus), originating in an Indian soil sample, and which has a ribose moiety carrying fluorine at C4. 

The Toxic Principle of Poison Ivy and Related Plants C. R. Dawson, Rec. Chem. Prog., 1954,15, 39-53. 

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