The Total Synthesis of Gambierol

Johnson, Henry W. B.; Majumder, Utpal; Rainier, Jon D.

doi:10.1021/ja043396d

Cited by 100 publications

(63 citation statements)

References 27 publications

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“…Gambierol was synthesized as previously described (Johnson et al, 2005. Synthetic gambierol was identical spectroscopically (NMR 13C and 1H, MS, IR) to natural gambierol.…”

Section: Compound Synthesismentioning

confidence: 99%

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Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels

Cuypers

Abdel–Mottaleb

Kopljar

et al. 2008

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“…Gambierol was synthesized as previously described (Johnson et al, 2005. Synthetic gambierol was identical spectroscopically (NMR 13C and 1H, MS, IR) to natural gambierol.…”

Section: Compound Synthesismentioning

confidence: 99%

“…Synthetic gambierol was identical spectroscopically (NMR 13C and 1H, MS, IR) to natural gambierol. For all the relevant spectral data see Johnson et al (2005). The sample was dissolved in dimethyl sulfoxide (DMSO) and diluted with ND96.…”

Section: Compound Synthesismentioning

confidence: 99%

Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels

Cuypers

Abdel–Mottaleb

Kopljar

et al. 2008

Toxicon

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“…The chemical synthesis of gambierol has facilitated the investigations into the pathologic and pharmacological characterization of this compound (Fuwa et al, 2002(Fuwa et al, , 2004Johnson et al, 2005;Furuta et al, 2010). Gambierol is a potent toxin with a minimal lethal dose ranging from 50 to 80 mg/kg (i.p.)…”

Section: Introductionmentioning

confidence: 99%

Gambierol Inhibition of Voltage-Gated Potassium Channels Augments Spontaneous Ca²⁺Oscillations in Cerebrocortical Neurons

Cao

Cui

Busse

et al. 2014

J Pharmacol Exp Ther

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Gambierol is a marine polycyclic ether toxin produced by the marine dinoflagellate Gambierdiscus toxicus and is a member of the ciguatoxin toxin family. Gambierol has been demonstrated to be either a low-efficacy partial agonist/antagonist of voltage-gated sodium channels or a potent blocker of voltage-gated potassium channels (K v s). Here we examined the influence of gambierol on intact cerebrocortical neurons. We found that gambierol produced both a concentration-dependent augmentation of spontaneous Ca 21 oscillations, and an inhibition of K v channel function with similar potencies. In addition, an array of selective as well as universal K v channel inhibitors mimicked gambierol in augmenting spontaneous Ca 21 oscillations in cerebrocortical neurons. These data are consistent with a gambierol blockade of K v channels underlying the observed increase in spontaneous Ca 21 oscillation frequency. We also found that gambierol produced a robust stimulation of phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2). Gambierol-stimulated ERK1/2 activation was dependent on both inotropic , a phospholipase C inhibitor, both suppressed gambierol-induced ERK1/2 activation, further confirming the role of type I mGluR-mediated signaling in the observed ERK1/2 activation. Finally, we found that gambierol produced a concentration-dependent stimulation of neurite outgrowth that was mimicked by 4-aminopyridine, a universal potassium channel inhibitor. Considered together, these data demonstrate that gambierol alters both Ca 21 signaling and neurite outgrowth in cerebrocortical neurons as a consequence of blockade of K v channels.

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“…[135] Rainier und Mitarbeiter machten vor kurzem bei ihrer Totalsynthese des Polyethertoxins Gambierol (135, Schema 25) Gebrauch von dieser Tandemsequenz aus Methylenierung und Ringschlussmetathese. [136] Die konvergente Strategie sah es vor, zunächst separate ABC-und FGH-Ring-Fragmente zu synthetisieren und diese anschließend durch eine intermolekulare Veresterung zu vereinen. Ringschlussmetathesen von Enolethern halfen beim Aufbau der Untereinheiten durch Bildung der Ringe B, C und F. [137] Die Ringschlussmetathese zum F-Ring war besonders bemerkenswert, wenn man berücksichtigt, dass dabei eine sterisch befrachtete tetrasubstituierte AlkenEinheit aufgebaut wurde.…”

Section: Aufsätze Dung Und Ihrem Benachbarten Partner Folgen (118!119)unclassified

“…. [136] Metathesereaktionen Angewandte Chemie rings vollständig auf das neu gebildete Pyransystem übertragen wird. [140] Interessanterweise induzierte der Katalysator 2 der ersten Generation die gewünschte Reaktion nicht, obwohl er bei analogen Metathesen mit weniger gehinderten Substraten erfolgreich war.…”

Section: Aufsätze Dung Und Ihrem Benachbarten Partner Folgen (118!119)unclassified

Metathesereaktionen in der Totalsynthese

2005

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Mit Ausnahme der palladiumkatalysierten Kreuzkupplungsreaktionen hatte im vergangenen Vierteljahrhundert keine Reaktionsklasse einen derart weitreichenden Einfluss auf die Kohlenstoff‐Kohlenstoff‐Verknüpfung und die Totalsynthese wie die Metathesereaktionen von Olefinen, Eninen, und Alkinen. In diesem Aufsatz präsentieren wir Glanzlichter aus einer Reihe ausgewählter Totalsynthesen, in denen diese eleganten und effizienten Reaktionen entscheidend zum Erfolg beigetragen haben. Schon an ihrer kurzen, aber beeindruckenden Geschichte kann man ablesen, dass die Bedeutung dieser Reaktionen für die chemische Synthese weiter zunehmen wird.

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The Total Synthesis of Gambierol

Abstract: This communication describes the total synthesis of the marine polyether toxin, gambierol. This work couples our iterative C-glycoside/enol ether-olefin metathesis strategy to the subunits with a unique olefin metathesis/carbonyl olefination reaction to bring the subunits together.

Cited by 100 publications

References 27 publications

Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels

Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels

Gambierol Inhibition of Voltage-Gated Potassium Channels Augments Spontaneous Ca²⁺Oscillations in Cerebrocortical Neurons

Metathesereaktionen in der Totalsynthese

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The Total Synthesis of Gambierol

Abstract: This communication describes the total synthesis of the marine polyether toxin, gambierol. This work couples our iterative C-glycoside/enol ether-olefin metathesis strategy to the subunits with a unique olefin metathesis/carbonyl olefination reaction to bring the subunits together.

Cited by 100 publications

References 27 publications

Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels

Gambierol, a toxin produced by the dinoflagellate Gambierdiscus toxicus, is a potent blocker of voltage-gated potassium channels

Gambierol Inhibition of Voltage-Gated Potassium Channels Augments Spontaneous Ca2+Oscillations in Cerebrocortical Neurons

Metathesereaktionen in der Totalsynthese

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Gambierol Inhibition of Voltage-Gated Potassium Channels Augments Spontaneous Ca²⁺Oscillations in Cerebrocortical Neurons