Synthesis of Anatoxin via Cyclization of Cyclooctenes

When contemplating structural modification of a potent ligand,such as anatoxin-a, two important issues must be addressed andbalanced against one another. Firstly, what site of the ligand'sskeleton will tolerate substitution and, in the process, retaineffective biological potentcy? Secondly, are suitable syntheticmethods available for achieving the chemical activation requiredto append a substituent or spacer unit at this site?

Synthesis of Anatoxin-a via Enantioselective Enolization Strategy
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In the same year JP Devlin and colleagues discovered the bicyclic secondary amine structure of anatoxin-a. They also performed experiments similar to those of Carmichael et al. on mice. They found that anotoxin-a kills mice 2–5 min after intraperitoneal injection preceded by twitching, muscle spasms, paralysis and respiratory arrest. They determined the for mice to be 250 microgam/kg body weight.

Synthesis of Anatoxin-a via Enyne Metathesis

Synthesis of Anatoxin-a via Intramolecular Cyclization of Iminium Ions
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Despite its poisonous nature, however, anatoxin and many related man-made analogues have found widespread use in medicine and for pharmacological applications.

()-Anatoxin A fumarate, Tocris 1mg - Fisher Scientific

Modified analogues are being used in order to further elucidate the receptor sub-types, and this research may lead to the development of new drugs which have none of the toxicity associated with anatoxin itself, but which act merely as acetylcholine replacement candidates.

(±)-Anatoxin A fumarate, Tocris™ ..

Cyclisation of Iminium SaltsRapoport's synthesis of anatoxin relied on the formation of a reactive iminium ion, which was generated by a Lewis acid-induced decarboxylation.

(±)-Anatoxin A fumarate: Safety and Handling.

1984, 106, 7979).A new synthetic strategy for the synthesis of an early intermediate in the Gallagher route to anatoxin employed the cyclisation of allenes using silver tetrafluoroborate (J.

T3D4124: Identification; Common Name: Anatoxin a: ..

Reaction of the β-lactam with a variety of nucleophiles, followed by selenium-mediated cyclisation and oxidation gave the skeleton of anatoxin- a bearing various sidechains.

Anatoxin-a is not to be confused with anatoxin-a(S), ..

AB - Aspergillus parasiticus is one primary source of anatoxin contamination in economically important crops. To prevent the potential health and economic impacts of anatoxin contamination, our goal is to develop practical strategies to reduce aflatoxin synthesis on susceptible crops. One focus is to identify biological and environmental factors that regulate aflatoxin synthesis and to manipulate these factors to control aflatoxin biosynthesis in the field or during crop storage. In the current study, we analyzed the effects of aspergillus volatiles on growth, development, aflatoxin biosynthesis, and promoter activity in the filamentous fungus A. parasiticus. When colonies of Aspergillus nidulans and A. parasiticus were incubated in the same growth chamber, we observed a significant reduction in aflatoxin synthesis and asexual sporulation by A. parasiticus. Analysis of the headspace gases demonstrated that A. nidulans produced much larger quantities of 2-buten-1-ol (CA) and 2-ethyl-1-hexanol (EH) than A. parasiticus. In its pure form, EH inhibited growth and increased aflatoxin accumulation in A. parasiticus at all doses tested; EH also stimulated aflatoxin transcript accumulation. In contrast, CA exerted dose-dependent up-regulatory or down-regulatory effects on aflatoxin accumulation, conidiation, and aflatoxin transcript accumulation. Experiments with reporter strains carrying nor-1 promoter deletions and mutations suggested that the differential effects of CA were mediated through separate regulatory regions in the nor-1 promoter. The potential efficacy of CA as a tool for analysis of transcriptional regulation of aflatoxin biosynthesis is discussed. We also identify a novel, rapid, and reliable method to assess nor-solorinic acid accumulation in solid culture using a Chroma Meter CR-300 apparatus.