Antillatoxin
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 Three-dimensional representation of antillatoxin
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IUPAC name
(6S,9S,14R,15R)-7,9,14-Trimethyl-13-methylidene-6-propan-2-yl-15-[(2E,4E)-4,6,6-trimethylhepta-2,4-dien-2-yl]-1-oxa-4,7,10-triazacyclopentadecane-2,5,8,11-tetrone
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| Other names
ATX
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3D model (Jmol)
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PubChem CID
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| Properties | |
| C28H45N3O5 | |
| Molar mass | 503.674 |
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Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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| Infobox references | |
Antillatoxin (ATX) is a potent lipopeptide neurotoxin produced by the marine cyanobacterium Lyngbya majuscula. ATX activates voltage-gated sodium channels, which can cause cell depolarisation, NMDA-receptor overactivity, excess calcium influx and neuronal necrosis.
Antillatoxin is found in the venom of the marine cyanobacterium Lyngbya majuscula. The filamentous cyanobacterium grows on seagrass, macroalgae, and corals up to 30m deep in tropical and subtropical regions throughout the world.
The three dimensional NMR study of this toxin showed that it consists of a tripeptide glycine-N-methylvaline-alanine, a hydroxycarboxylic acid and a 9-t-butyl-6,8-dimethyl-6,8-diene attached to the C5 atom of the cyclic peptide backbone.
There are three known analogous structures of ATX which have different toxicity: antillatoxin B (8-demethyl-antillatoxin) and DH-ATX (8-demethyl-8,9-dihydro-antillatoxin), and various stereoisomers of antillatoxin A. These various structures have been found to be less toxic than antillatoxin A. Synthetic versions of antillatoxin have been produced with conformational variations of the lipophilic side chain. All of these structures drastically changed the toxins activity. Structures where the C7-C8=C9 bond angle was closer to 180o showed lower levels of toxicity in cell cultures. Structures that added a bulky side group to the C5 position also showed dramatic decreases in toxicity, including loss of activity.
The figure below shows the first total synthesis of antillatoxin by Yokokawa et al in 1998. (2E,4E)-2,4,6,6-Tetramethyl-2,4-heptadien-1-ol was transformed using a stereoselective aldol reaction, followed by the addition of a triethylsilyl protecting group. This allowed for cleavage of the chiral auxiliary of the ester. TPAP oxidation followed by Still’s olefination and protonation leads to the lactone. After transformation into the phenylselenyl derivative, alkaline cleavage, allyl esterification and coupling with the tripeptide yields the ester. Oxidation leads to the linear product, which is tranformed into antillatoxin by deprotection at the N and C terminals and macrolactimization with DPPA.
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