Hepatotoxins cyanobacterial

Perhydropyrido[l,2-r]pyrimidin-l,3-ones were applied in the total synthesis of cyanobacterial hepatotoxin 7-epicylindrospermopsin (01JA8851). 

Pelander et al. [71] studied the retardation behavior of cyanobacterial hepato-toxins in the irregular part of the PRISMA model for TLC at 16 selectivity points. The mobile phase combination and the area of the triangular plane were selected in the preassay. The retardation of all the toxins followed the relation for ftRp. The cyanobacterial hepatotoxins behaved predictably in the selected systems in the irregular part of the PRISMA model. 

Pelander et al. [81] developed a computer program for optimization of the mobile phase composition in TLC. They used the desirability function technique combined with the PRISMA model to enhance the quahty of TLC separation. They apphed the statistical models for prediction of retardation and band broadening at different mobile phase compositions they obtained using the PRISMA method the optimum mobile phase mixtures and a good separation for cyanobacterial hepatotoxins on a normal phase TLC plate and for phenolic compound on reversed-phase layers. 

Fig. 5.1 Common cyanobacterial hepatotoxins. (a) Generalized structure of microcystin, a cyclic heptapeptide. Note that X and Z are L-amino acids. For example, microcystin-LR possesses lysine and arginine residues at X and Z, respectively, (b) Cylindrospermopsin, a hepatotoxic alkaloid from Cylindrospermopsis raceborskii...

Moffitt MC, Neilan BA (2004) Characterization of the nodularin synthetase gene cluster and proposed theory of the evolution of cyanobacterial hepatotoxins. Appl Environ Microbiol... 

McElhiney J, Lawton LA (2005) Detection of the cyanobacterial hepatotoxins microcystins. Toxicol Appl Pharmacol 203 219-230... 

This procedure was successfully used as part of the total synthesis of the freshwater cyanobacterial hepatotoxins cylindrospermopsin 741 and 7-epicylindrospermopsin 742 <2001JA8851, 2002JA3939>. 

A. Pelander, I. Ojanpera, K. Lahti, K. Niinivaara and E. Vuori, Visual detection of cyanobacterial hepatotoxins by thin-layer chromatography and application to water analysis, Water Res., 10 (2000) 2643-2652. 

H. Siren, M. Jussila, H. Liu, S. Peltoniemi, K. Sivonen and M.-L. Riek-kola, Separation, purity testing, and identification of cyanobacterial hepatotoxins with capillary electrophoresis and electrospray mass spectrometry, J. Chromatogr. A, 839 (1999) 203-215. 

The hydrolytic lability of N.O-acetals varies widely. One extreme is exemplified by a synthesis of the cyanobacterial hepatotoxin Cylindrospermopsin [Scheme 8.157]345 in which hydrolysis of the oxazolidine ring in 157.1 required HCI in aqueous THF at 85 °C The penultimate step in the synthesis required hydrolysis of two N-MOM groups on the uracil ring but the positively charged guanidi-nium salt 157.3 thwarted a second protonation required for the hydrolysis hence, 12 M HCI at 95 °C was required to secure the product 157 4. 

The effects of cyanobacterial hepatotoxins and neurotoxins were examined on the embryos of fish and amphibians up to advanced stages of embryonic development. No acute toxic effects were observed after exposure to microcystins, but at the highest applied concentration of microcystin-LR (10 mg/L), morphological effects were detected. AN (400 pg/L) altered the heart rate in zebrafish, but no chronic effects were observed (Oberemm et al. 1999). The effects of cyanobacterial toxins on... 

Rapala, J., Lahiti, K., Sivonen, K., and Niemelae, S.I. 1994. Biodegradability and adsorption on lake sediments of cyanobacterial hepatotoxins and anatoxin-a. Lett Appl Microbiol 19, 423 28. 

Heresztyn, T, Nicholson, B.C. 2001. Determination of cyanobacterial hepatotoxins directly in water using a protein phosphatase inhibition assay. Water Res 13 3049-3056. 

McElhiney I, Lawton L. A. 2005. Detection of cyanobacterial hepatotoxins microcystins. Toxicology and Applied Pharmacology 263 2X9-236. 

Ojanpera, I., Pelander, A., Vuori, E., Himberg, K., Waris, M., and Niinivaara, K. 1995. Detection of cyanobacterial hepatotoxins by TLC. Journal of Planar Chromatog 8 69-72. 

Pelander, A., Ojanpera, I., and Vuori, E. 1998. Analysis of cyanobacterial hepatotoxins by overpressured layer chromatography. Joitmai of Planar Chromatography. 11 365-369. 

In 2002 the same author demonstrated the usefulness of this method in a rather demanding context including an intramolecular cycloaddition with an W-sulfinyl urea as a new type of N-sulfinyl dienophile (Scheme 60) [144]. As key steps in the total synthesis of freshwater cyanobacterial hepatotoxins, ( , )-diene 238 was transformed into N-sulfinyl urea 239 which immediately cycloadds intramolecularly yielding tricycle 240 as a single isomer in excellent yield. After reaction with phenylmagnesium bromide the intermediate allylic sulfoxide rearranges cleanly to diastereomerically pure allylic alcohol... 

Purification of Cyanobacterial Hepatotoxin Microcystins by Affinity Chroi Fumio Kondo... 

S.M.F.O. Microcystins (cyanobacterial hepatotoxins) bioaccumulation in fish and crustaceans from Sepetiba Bay (Brazil, RJ), Toxicon, 42, 289, 2003. 

Pflugmacher, S., Wiegand, C., Oberemm, A., Beattie, K.A., Krause, E., Codd, G.A. and Steinberg, C.E.W. Identification of the enzymatically formed glutathione conjugate of the cyanobacterial hepatotoxin microcystin-LR the first step of detoxification, Biochem. Biophys. Acta., 1425, 527, 1998. 

Sipia, V.O., Kankaanpaa, H.T., Flinkman, J., Lahti, K. and Meriluoto, J. Time-dependent accumulation of cyanobacterial hepatotoxins in flounder (Platichthys flesus) and mussels (Mytelis edulis), from the northern Baltic Sea, Environ. Toxicol., 16, 330, 2001b. 

Advances in analytical techniques allowed the identification of the toxins (see below) in the 1980s and subsequent routine analyses of water samples showed that cyanobacterial hepatotoxins are likely to be detected in any water body carrying a cyanobacterial bloom. 

Although cyanobacterial hepatotoxins have been studied intensively under many aspects in the last three decades, the role of the compounds in the cyanobacteria s physiology and ecology is stiU not evident. 

The question whether cyanobacterial hepatotoxins constitute a human health risk is still debated and is not easy to answer since in comparison to other waterborne diseases, e.g., cholera epidemics, the number and severity of cyanotoxin related illnesses appears less dramatic. On the other hand, microcystins and cylindrospermopsins are potent toxins with LD50S similar to or even lower than that of some of the most notorious natural toxins, like a-amanitin (Amanita phalloides), strychnine (Strychnos nux-vomica), or aconitine (Aconitum sp.). Compared to these natural toxins, exposure to cyanobacterial toxins is much harder to avoid and the cyanotoxin-related epidemics indicate that potentially a large number of people can be affected when, for example, drinking water is contaminated. Among chemicals to which humans are exposed through water, cyanobacterial toxins probably occur most frequently in a global perspective. 

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