Okadaic acid

Okadaic acid
Names
	IUPAC name (2R)-3-[(2S,6R,8S,11R)-2-[(E,1R)-3-[(2S,2'R,4R,4aS,6R,8aR)-4-hydroxy-2-[(1S,3S)-1-hydroxy-3-[(2S,3R,6S)-3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl]butyl]-3-methylene-spiro[4a,7,8,8a-tetrahydro-4H-pyrano[2,3-e]pyran-6,5'-tetrahydrofuran]-2'-yl]-1-methyl-prop-2-enyl]-11-hydroxy-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-hydroxy-2-methyl-propanoic acid
	Systematic IUPAC name (2R)-3-[(2S,6R,8S,11R)-2-[(E,1R)-3-[(2S,2'R,4R,4aS,6R,8aR)-4-hydroxy-2-[(1S,3S)-1-hydroxy-3-[(2S,3R,6S)-3-methyl-1,7-dioxaspiro[5.5]undecan-2-yl]butyl]-3-methylene-spiro[4a,7,8,8a-tetrahydro-4H-pyrano[2,3-e]pyran-6,5'-tetrahydrofuran]-2'-yl]-1-methyl-prop-2-enyl]-11-hydroxy-4-methyl-1,7-dioxaspiro[5.5]undec-4-en-8-yl]-2-hydroxy-2-methyl-propanoic acid
Identifiers
CAS Number	78111-17-8;
3D model (JSmol)	Interactive image;
ChEBI	CHEBI:CHEBI:7733;
ChemSpider	393845;
ECHA InfoCard	100.116.145
MeSH	Acid Okadaic Acid
PubChem CID	446512;
CompTox Dashboard (EPA)	DTXSID60880002 ;
	InChI InChI=1S/C44H68O13/c1-25-21-34(55-44(23-25)35(46)12-11-31(54-44)24-41(6,50)40(48)49)26(2)9-10-30-14-18-43(53-30)19-15-33-39(57-43)36(47)29(5)38(52-33)32(45)22-28(4)37-27(3)13-17-42(56-37)16-7-8-20-51-42/h9-10,23,26-28,30-39,45-47,50H,5,7-8,11-22,24H2,1-4,6H3,(H,48,49)/b10-9+/t26-,27-,28+,30+,31+,32+,33-,34+,35-,36-,37+,38+,39-,41-,42+,43-,44-/m1/s1;
	SMILES O=C(O)[C@@](O)(C)C[C@H]7O[C@]/1(O[C@@H](CC(=C\1)\C)[C@@H](/C=C/[C@@H]6O[C@@]3(O[C@H]2[C@H](O)/C(=C)[C@H](O[C@@H]2CC3)[C@@H](O)C[C@H](C)[C@H]5O[C@]4(OCCCC4)CC[C@H]5C)CC6)C)[C@H](O)CC7;
Properties
Chemical formula	C44H68O13
Molar mass	805.00
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Okadaic acid is a toxin that accumulates in bivalves and causes diarrhetic shellfish poisoning. The molecular formula of okadaic acid, which is a derivative of a C₃₈ fatty acid, is C₄₄H₆₈O₁₃. The IUPAC name of okadaic acid is (2R)-2-hydroxy-3-{(2S,5R,6R,8S)-5-hydroxy-[(1R,2E)-3-((2R,5R,6'S,8'R,8a'S)-8'-hydroxy-6'-{(1S,3S)-1-hydroxy-3-[(3R,6S)-3-methyl-1,7-dioxaspiro[5.5]undec-2-yl]butyl}-7'-methyleneoctahydro-3H,3'H-spiro[furan-2,2'-pyrano[3,2-b]pyran]-5-yl)-1-methylprop-2-en-1-yl]-10-methyl-1,7-dioxaspiro[5.5]undec-10-en-2-yl}-2-methylpropanoic acid.

Okadaic acid was named from the marine sponge Halichondria okadai, from which okadaic acid was isolated for the first time. It has also been isolated from another marine sponge, H. malanodocia, as a cytotoxin. The real producer of okadaic acid is a marine dinoflagellate.

Administration of okadaic acid has been shown to profoundly increase the secretion of nerve growth factor, and to also promote nerve growth factor gene transcription and the stability of mRNA in primary cultures of cortical astrocytes.^[1]

The cytotoxicities of okadaic acid as EC50 against the P388 and L1210 cell lines are 1.7 nanomolar and 17 nanomolar, respectively. Additionally, okadaic acid strongly inhibits protein serine / threonine phosphatase 1, 2A, and 2B^[2]. The inhibitory effect of okadaic acid is strongest for 2A, followed by 1, and then 2B. The dissociation constant of the inhibition on protein serine / threonine phosphatase 2A is 30 pico-molar.

Footnotes

^ Pshenichkin, S. P., B. C. Wise. (17 March 1995) Okadaic Acid Increases Nerve Growth Factor Secretion, mRNA Stability, and Gene Transcription in Primary Cultures of Cortical Astrocytes. Journal of Biological Chemistry. Vol. 270, Num. 11. pp. 5994-5999.
^ Alphonse Garcia, Xavier Cayla, Julien Guergnon, Frédéric Dessauge, Véronique Hospital, Maria Paz Rebollo, Aarne Fleischer and Angelita Rebollo (2003). "Serine/threonine protein phosphatases PP1 and PP2A are key players in apoptosis". Biochimie. 85 (8): 721–726. doi:10.1016/j.biochi.2003.09.004.{{cite journal}}: CS1 maint: multiple names: authors list (link)

References

Kazuo Tachibana, Paul J. Scheuer, Yasumasa Tsukitani, Hiroyuki Kikuchi, Donna Van Engen, Jon Clardy, Yalamanchili Gopichand, and Francis J. Schmitz (1981). "Okadaic acid, a cytotoxic polyether from two marine sponges of the genus Halichondria". Journal of the American Chemical Society. 103 (9): 2469–2471. doi:10.1021/ja00399a082.{{cite journal}}: CS1 maint: multiple names: authors list (link)
Forsyth, C. J.; Sabes, S. F.; Urbanek, R. A. (1997). "An Efficient Total Synthesis of Okadaic Acid". Journal of the American Chemical Society. 119 (35): 8381–8382. doi:10.1021/ja9715206.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[1] Pshenichkin, S. P., B. C. Wise. (17 March 1995) Okadaic Acid Increases Nerve Growth Factor Secretion, mRNA Stability, and Gene Transcription in Primary Cultures of Cortical Astrocytes. Journal of Biological Chemistry. Vol. 270, Num. 11. pp. 5994-5999.

[2] Alphonse Garcia, Xavier Cayla, Julien Guergnon, Frédéric Dessauge, Véronique Hospital, Maria Paz Rebollo, Aarne Fleischer and Angelita Rebollo (2003). "Serine/threonine protein phosphatases PP1 and PP2A are key players in apoptosis". Biochimie. 85 (8): 721–726. doi:10.1016/j.biochi.2003.09.004.{{cite journal}}: CS1 maint: multiple names: authors list (link)

[1]

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