Very fast death factor

The use of nitrones in the synthesis of anatoxin-a, very fast death factor. Tetrahedron 41, 3447-3453, and references therein about the regioselectivity of nitrone cyclization. 

Interestingly, the balance can be tipped toward formation of the seven-membered ring by simply placing an electron-withdrawing group on the terminal carbon of the dipolarophile (Scheme IS). Tliis leads to polarization of the alkene and to an FMO-controlled process. Incidentally, the reaction shown proved critical in a total synthesis of anatoxin a, the so-called very fast death factor . ... 

The opening of halocyclopropanes to allyl systems according to equation 124 can happen thermally or with the assistance of electrophiles and nucleophiles . Some recent examples include an efficient cyclopentenone synthesis (equation 125) ", an electrocyclic opening/cyclization sequence giving functionalized furan and pyran derivatives (equation 126), an elegant total synthesis of the very fast death factor alkaloid ( ) anatoxin and a nice application of the well known nucleophilic opening to the preparation of crystalline methylene aziridines (equation 127) . 

Cyanobacteria toxins (sometimes referred to as blue green algal toxins) are represented in this entry by Aplysiatoxins, which are toxic to the skin, and anatoxin a (CAS 64285-06-9, C10H15NO) and anatoxin a (S) (very fast death factor), which are neurotoxins. Saxitoxin, discussed earlier, and neo-saxitoxin are both neurotoxins that may also be classified as cyanobacterial toxins. A large variety of other toxins is produced by cyanobacteria, but is not as well documented. These include lyngbyatoxin (dermatotoxic) cyclic peptides predominantly microcystins, nodularins, and cylindro-spermopsin (hepatotoxins) endotoxins and other substances as yet undescribed, including additional tumor promoters. 

Anatoxin-a (very fast death factor) from the cyanobacterium Anabaena... 

Anatoxin A is the fast-acting and highly effective poison of the cyanobacterium Anabaenaflos-aquae, which is ubiquitous in freshwater. Anatoxin A, also known as Very Fast Death Factor , was isolated from Anabaenaflos-aquae in 1977 by Paul Gorham at the National Research CoimcU in Ottawa. [553,554] The structure had already been determined in 1972 by X-ray analysis of its N-acetyl derivative. [555] Later, the presence of anatoxin A was detected in a range of other toxic strains of Oscillatoria, Anabaena circinalis, Aphanizomenonflos-aquae, Cylindorsperum pp. and Raphidiopsis mediterranea. 

The structure and toxic symptoms of pinnamine resemble those of anatoxin-a (11) [19,20], a potent postsynaptic depolarizing neurotoxin known as very fast death factor (VFDF), and atropine [21], a representative suppressor of the... 

---