Gambierol
 |
|
| Names | |
|---|---|
|
IUPAC name
(2S,4S,4aS,5aR,6aS,7aR,9aS,10aR,11aS,13R,14S,16aR,17aS,18aR,19aS,20aR,21aS,22aR)-13-[(1Z,3Z)-1,3,6-Heptatrien-1-yl]-2-(3-hydroxypropyl)-4a,5a,14,17a,18a-pentamethyl-2,3,4,4a,5a,6,6a,7a,8,9,9a,10a,11,1 1a,13,14,16a,17a,18,18a,19a,20,20a,21a,22,22a-hexacosahydrooxepino[2,3:5',6']pyrano[2',3':5,6]pyrano[3,2-b]pyrano[2,3:5,6]pyrano[2,3:5',6']pyrano[2',3':5,6]pyrano[2,3-f]oxepine-4,14-diol
|
|
| Identifiers | |
| ChemSpider | |
|
PubChem CID
|
|
| Properties | |
| C43H64O11 | |
| Molar mass | 756.97 g·mol−1 |
|
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
|
|
| Infobox references | |
Gambierol is a marine polycyclic ether toxin which is produced by the dinoflagellate Gambierdiscus toxicus. Gambierol is collected from the sea at the Rangiroa Peninsula in French Polynesia. The toxins are accumulated in fish through the food chain and can therefore cause human intoxication. The symptoms of the toxicity resample those of ciguatoxins, which are extremely potent neurotoxins that bind to voltage-sensitive sodium channels and alter their function. These ciguatoxins cause ciguatera fish poisoning. Because of the resemblance, there is a possibility that gambierol is also responsible for ciguatera fish poisoning. Because the natural source of gambierol is limited, biological studies are hampered. Therefore chemical synthesis is required.
Gambierol is a ladder-shaped polyether, composed of eight ether rings, 18 stereocenters, and two challenging pyranyl rings having methyl groups that are in a 1,3-diaxial orientation to one another. Different structural analogues were synthesized to determine which groups and side chains attached to the gambierol are essential for its toxicity. Not only the fused polycyclic ether core is essential, but also the triene side chain at C51 and the C48-C49 double bond were indispensable. In the triene side chain, the double bond between C57 and C58 was essential. The C1 and C8 hydroxy groups were not essential, but they enhance the activity. The conjugate diene in the triene side chain also enhances the toxicity.
The synthesis of gambierol consists of two tetracyclic precursor molecules, one alcohol and one acetic acid, that fuse together. The whole synthesis of gambierol is depicted in the figure below. After obtaining the octacyclic backbone, the tail is added via Stille coupling. The acetic acid (compound 1) and alcohol (compound 2) are converted to compound 3. The reaction of compound 3 with the titanium alkylidene from dibromide 1,1-dibromoethane, provides cyclic enol ether (compound 4). Oxidation of the alcohols gives majorly compound 5, but also compound 6. This are both ketones, but they have other stereochemistry. Compound 6 can be converted back in compound 5 with reactant c, thereby moving the equilibrium towards compound 5. This ketone can be converted further to produce reactive gambierol. By reductive cyclization of the D ring, the octacyclic core structure (compound 7) was made. Oxidation of compound 7 to the aldehyde was followed by formation of the diiodolefin. Stereoselective reduction, global deprotection and Stille coupling of compound 8 with dienyl stannane (compound 9) provide gambierol.
...
Wikipedia