Okadaic acid

Okadaic acid
IUPAC name (2R)-3-[(2S,6R,8S,11R)-2-[(E,1R)-3-[(2S,2&primeR,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
Other names 9,10-Deepithio-9,10-didehydroacanthifolicin
Identifiers
CAS number	78111-17-8
PubChem	446512
ChemSpider	393845
MeSH	Acid Okadaic Acid
ChEBI	CHEBI:CHEBI:7733
ChEMBL	CHEMBL176510
Jmol-3D images	Image 1
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
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 Key: QNDVLZJODHBUFM-WFXQOWMNSA-N InChI=1/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 Key: QNDVLZJODHBUFM-WFXQOWMNBB 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 Key: QNDVLZJODHBUFM-WFXQOWMNSA-N
Properties
Molecular formula	C44H68O13
Molar mass	805 g mol−1
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Okadaic acid is a toxin that accumulates in bivalves and causes diarrheal shellfish poisoning. The molecular formula of okadaic acid, which is a derivative of a C₃₈ fatty acid, is C₄₄H₆₈O₁₃.

History

Okadaic acid was named from the marine sponge Halichondria okadai, from which okadaic acid was isolated for the first time.^[1] It has also been isolated from another marine sponge, H. malanodocia, as a cytotoxin. The real producers of okadaic acid belong to the algae group of the dinoflagellates, namely the benthic dinoflagellate Prorocentrum and the planktonic forms of Dinophysis,^[2] as for example Dinophysis acuminata.^[3] 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.^[4]

Biochemistry

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.^[5] 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 picomolar.

References

1. ^ 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. 
2. ^ Lee, Robert Edward. Phycology, Cambridge University Press, 4th ed. 2008, ISBN 978-0521-68277-0
3. ^ "Dinophysis acuminata". www.algaebase.org. http://www.algaebase.org/search/species/detail/?species_id=52217. Retrieved 2010-05-04. 
4. ^ 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.
5. ^ 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. PMID 14585537. 

External links

• 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.