Isomer anatoxin

Using synthetic enantiomers, we found that anatoxin-a is highly stereospecific with the (+) isomer having 150-fold greater potency than the (-) isomer (Figure 2) 19). The semi-rigid nature of anatoxin-a undoubtedly facilitates its stereospecificity. 

Figure 2. Potency of anatoxin-a analogs to induce contracture in frog rectus abdominis muscle. The data from two experiments are combined in this figure. In one, anatoxinmethylester was found to be equipo-tent with carbamylcholine. In the other, the anatoxin isomers were assayed against ACh [after cholinesterse inhibition by diisopropylfluoro-phosphate (DFP) followed by washing of the preparation] (19). Maximal contracture was measured by depolarization with KCl at the end of each experiment.

Cyanobacteria toxins are toxins produced by certain species of blue-green algae that have become a major environmental and public health concern. The behavior of cyanotoxins during chlorination treatment has been recently reviewed by Merel et al. [129]. Chlorination DBFs have been reported only for the hepatotoxins microcystin-LR and cylindrospermopsin. Other cyanotoxins, such as nodularins, saxitoxins, and anatoxins, have yet to be investigated. Different isomers of six chlorination products of microcystin-LR have been characterized dihydroxy-microcystin, monochloro-microcystin, monochloro-hydroxy-microcystin, monochloro-dihydroxy-microcystin, dichloro-dihydroxy-microcystin, and trichloro-hydroxy-microcystin. Only two chlorination DBFs have been reported so far for cylindrospermopsin 5-chloro-cylindros-permopsin and cylindrospermopsic acid [129]. Chlorination of microcystin, cylindrospermopsin, and nodularins seems to reduce the mixture toxicity however, this aspect has not been extensively studied [129]. 

Swanson, K.L., Aracava, Y, Sardina, EJ., Rapoport, H., Aronstam, R. S., and Albuquerque, E.X. 1989. 77-Methylanatoxinol isomers, derivatives of the agonist (+)-anatoxin-a block the nicotinic acetylcholine-receptor ion channel. Mol Pharmacol 35, 22-3-2-31. 

Dar, D.E., and Zinder, O. 1998. Catecholamine secretion from bovine adrenal chromaffin cells induced by the dextrorotatory isomer of anatoxin-a. Gen Pharmacol 31, 737-740. 

Carbenes generated the more traditional way react similarly. In Trost s synthesis of (-)-anatoxin,297 the alkene unit in 366 reacted with dibromocarbene, generated from bromoform and base, to give an 85% yield of 367 and 368 as a 3.5 1 mixture of exo and endo isomers. 

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