Okadaic acid: A proton and carbon NMR study

doi:10.1016/S0040-4020(01)89745-3

Tetrahedron

Volume 47, Issue 35, 26 August 1991, Pages 7437-7446

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Abstract

Okadaic acid is an extremely interesting toxin responsible for diarrhetic shellfish poisoning (DSP). This interest is due not only to its fascinating structure but also to its unknown biosynthetic origin. In this paper we report on the full NMR study of this molecule including the appropriate 2D homo and heteronuclear NMR experiments neccesary to carried out its biosynthetic study.

Okadaic acid is an extremely interesting toxin responsible for diarrhetic shellfish poisoning (DSP). This interest is due not only to its fascinating structure but also to its unknown biosynthetic origin. In this paper we report on the full NMR study of this molecule, including the appropriate 2D homo and heteronuclear NMR experiments, necessary to carried out its biosynthetic study.

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The use of okadaic acid to elucidate the intracellular role(s) of protein phosphatase 2A: Lessons from the mast cell model system
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In recent years a heightened appreciation has emerged for the role(s) that phosphatases play in regulating signal transduction pathways and other cellular processes. The tumor-promoting agent okadaic acid (OA) has been an invaluable tool in efforts aimed at delineating the contributions of the most abundant mammalian serine/threonine phosphatase, protein phosphatase 2A (PP2A), to intracellular signaling and cell function. PP2A, which is ubiquitous and vital in virtually every cell system studied, continues to be the focus of much research on phosphorylation control machinery. Mast cells represent an excellent in vitro model for the study of protein phosphorylation events because they possess a number of distinct signaling pathways that lead to the production and/or release of discreet mediators in response to different stimuli. The utility of OA in analyzing PP2A function has been demonstrated in mast cells across several species. Results of these studies have contributed to the current recognition that PP2A plays a crucial role in the biology of mast cells and other cell types.
Importance of the C28-C38 hydrophobic domain of okadaic acid for potent inhibition of protein serine-threonine phosphatases 1 and 2A
2001, Bioorganic and Medicinal Chemistry Letters
Carbohydrate-modified fused pyranosylidene complexes via radical addition of epoxides to unsaturated metal carbenes
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Alkenyl and alkynyl carbene complexes of chromium and tungsten undergo a diastereoselective cyclization upon reaction with epoxides in presence of [Cp₂TiCl]₂. trans-Fused tetrahydropyranosylidene complexes are obtained from the radical addition of cyclohexene oxide to monosaccharide-derived vinylcarbene tungsten complexes. The benzyl-protected 1,2-anhydro-α-d-glucopyranose adds to styryl and alkynyl carbene complexes to give bicyclic trans-fused tetrahydro- and dihydropyranosylidene complexes as well as the acyclic addition products.
Complexation of okadaic acid: A preliminary study
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Effects of okadaic acid on the human isolated bronchus
1994, European Journal of Pharmacology
The effects of okadaic acid, a polyether derivative of a 38-carbon monocarboxylic fatty acid obtained from a culture of the marine dinoflagellate, Prorocentrum lima, were studied on the human isolated bronchus. In low concentrations (0.01 and 0.03 μM), okadaic acid had no significant effect of its own on the human isolated bronchus, but in higher concentrations (0.1–10 μM) it induced a series of contractions and relaxations. The first contraction was of low intensity (5% of maximum response to acetylcholine 3 mM) and occured early. The second contraction had a higher amplitude (30% of maximum response to acetylcholine 3mM) and reached its peak with okadaic acid 0.3 μM. At higher concentrations (1–10 μM), following a relaxation phase, a later rebound contraction occurred between 70 and 120 min and corresponded to 40% of the maximum response to acetylcholine 3 mM. In addition, okadaic acid inhibited or abolished the contractile response evoked by either KCl 60 mM or acetylcholine 3 mM with IC₅₀ of 0.04 and 0.12 μM, respectively. The second contraction evoked by 0.3 μM okadaic acid was partially inhibited in the presence of the Ca²⁺ channel blocker, nicardipine 1 μM, or after incubation of the human bronchus in a Ca²⁺-free solution and it was completely abolished in the presence of CdSO₄ 0.1 mM. The non-specific smooth muscle relaxant, papaverine (1–15 μM), inhibited the second contractile response to okadaic acid 0.3 μM in the way it inhibited the KCl 60 mM- or the acetylcholine 3 mM-induced response. In contrast, caffeine (0.1–10 mM) inhibited or almost completely abolished this okadaic acid 0.3 μM-induced contraction at concentrations at which it failed to modify significantly or induced only a partial inhibition of the contractile responses to KCl 60 mM or acetylcholine 3 mM. Okadaic acid 1 μM did not affect the intracellular levels of phosphoinositides in the human isolated bronchus. To conclude, these results show that okadaic acid induces complex contractile and relaxant effects on the human isolated bronchus. Its contractile effect is independent of the phosphoinositide pathway; it seems to involve, at least partially, entry of Ca²⁺ into the cell and mobilization of intracellular Ca²⁺ from a caffeine-dependent pool, but other mechanisms may also be acting.
Studies on the biosynthesis of the polyether marine toxin dinophysistoxin-1 (DTX-1)
1994, Tetrahedron Letters

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Okadaic acid: A proton and carbon NMR study

Abstract

J. Am. Chem. Soc.

J. Am. Chem. Soc.

J. Am. Chem. Soc.

J. Am. Chem. Soc.

Tetrahedron

J. Am. Chem. Soc.

J. Am. Chem. Soc.

Polyether Antibiotics: Carboxylic Ionophores

J. Nat. Prod.

J. Am. Chem. Soc.

J. Am. Chem. Soc.

J. Am. Chem. Soc.