Of okadaic acid

In addition to okadaic acid, dinophysistoxin-1 (i.e., 35-methylokadaic acid), 7-0-palmitoyl-okadaic acid, and pectenotoxin 2 are reported to be diarrhetic toxins from shellfish 34). Application of 1 xg of dinophysistoxin-1 to mouse ear caused as strong irritation as the same dose of okadaic acid. Interestingly, the potencies of these compounds in the irritant test on mouse ear correlated well with their potencies as diarrhetic shellfish poisons. Dinophysistoxin-1 induced ODC activity as strongly as okadaic acid. Recently, we found that dinophysistoxin-1 is also a new non-TPA type tumor promoter with as high activity as okadaic acid 35). 

Surprisingly few studies have been performed with purified toxins. When added externally to the water, toxins of various origins were tested on the cope-pod Tigriopus californicus. The protein phosphatase inhibitor okadaic acid (17) from red tide dinoflagellates [22] and the neuronal depolarizing agent do-moic acid (10) from diatoms [40, 41] had different effects on the herbivores (Scheme 3). Micromolar concentrations of okadaic acid (17) acted both as toxin... 

Scheme 5 Release of okadaic acid (17) from less toxic precursors by E. lima (left). Oxidative transformation of okadaic acid diol ester (16) by the diatom Thalassiosira weissflogii (right)...

The cytotoxicities of okadaic acid as EC50 against the P388 and L1210 cell lines are 1.7 nano-molar and 17 nano-molar, respectively. Additionally, okadaic acid strongly inhibits protein serine/threonine phosphatase 1,2A,... 

Urbanek RA, Sabes SF, Forsyth CJ, Efficient synthesis of okadaic acid 1. Convergent assembly of the C15-C38 domain, J Am Chem Soc 120 2523—2533, 1998. 

Properties of toxins. Dinophysistoxin-1 was isolated as a white amorphous solid m.p. 134 C ] +28 (c 0.046, chloroform) Rf in TLC 0.42 minimum lethal dose to mouse 160 ig/kg (i.p.). El mass spectrum gave a dehydrated ion peak at m/z 800, pointing to a composition C45H5gOi2 Overall features of both PMR and CMR spectra of dinophys is toxin-1 closely resembled those of okadaic acid (I ) except the presence of an additional methyl in dinophysistoxin-1. Comparison of the spectra of okadaic acid and dinophysistoxin-1 and supplemental spin-spin decoupling measurements enabled us to assign dinophysistoxin-1 to 35(5)-methyl okadaic acid (II) (5). A component tentatively named dinophysistoxin-2 was slightly more polar than dinophysistoxin-1 but its characterization was unsuccessful due to the extreme smallness of the sample size. 

Solubility and chromatographic behavior of PC-1 were very similar to those reported for SG-1 (scarltoxin) from parrotfish (14), scaritoxln from the turban shell (38), and PL toxin II (scarltoxin-llke toxin) from lima (23). The possibility of PC-1 being a derivative of okadaic acid should not be overlooked. 

Table 4. Inhibitory effects (1C , pmol/L) of six flavonoids for the release of TNF-a from BALB/3T3 cells by treatment of okadaic acid...

Additional pharmacological studies on the cytotoxic compound acanthifolicin (95), the 9,10-episulfide derivative of okadaic acid obtained from sponge Pandaros acanthifolium [103], showed it to be an inhibitor of phosphatases 1 and 2a (PP1-1 and PP-2a) with similar potencies to okadaic acid [104]. 

Work Item I determination of okadaic acid and dinophysis toxin in mussels by HPLC. 

Fluorescence may by induced using labeled mono- or polyclonal antibodies raised against the compound of interest. This technique has been used successfully to detect the presence of okadaic acid in cultures of Prorocentrum lima, and, further, to estimate quantities of the compound in individual cells.110 Immunofluoresence in combination with thin layer chromatography and ELISA techniques have also been used to detect multiple haptens in mycotoxin families.111112... 

Tetrahydropyrans bearing halides at C4 can be accessed by a modified Taddei-Ricci reaction. The reaction involves condensation of allyltrimethylsilane, aldehydes and a cyclic acetal 371 in the presence of a Lewis acid to afford all ry -tetrahydropyrans 372 as a single diastereomer. The reaction proceeds via anion mediated ring closure of oxonium ion intermediate 373 (Scheme 89). This methodology was successfully applied to the synthesis of a model compound bearing all the structural motifs present in the eastern subunit of okadaic acid <1997TL2895>. 

Cembella, A.D. 1989. Occurrence of okadaic acid, a major diarrheic shellfish toxin, in natural populations of Dinophysis spp. from the eastern coast of North America JAppl Phycol 1, 307-310. 

Sato, S., Koike, K., and Kodama, M. 1996. Seasonal variation of okadaic acid and dinophysistoxin-1 in Dinophysis spp. in association with the toxicity of scallop. In Harmful and Toxic Algal Blooms, ed. Yasumoto, T, Oshima, Y, and Fukuyo, Y. Intergovernmental Oceanographic Commission of UNESCO, 285-288. 

Fernandez, M.L., Miguez, A., Cacho, E., and Martinez, A. 1996. Detection of okadaic acid esters in the hexane extracts of Spanish mussels. Toxicon, 34(3), 381-387. 

Kumagai, M., Yanagi, T, Murata, M., Yasumoto, T, Kat, M., Lassus, P, and Rodriguez-Vazquez, A., 1986. Identification of okadaic acid as the causative toxin of diarrhetic shellfish poisoning in Europe. Agric Biol Chem 50, 2853—2857. 

Murakami, Y, Oshima, Y, and Yasumoto, T. 1982. Identification of okadaic acid as atoxic component of a marine dinoflagellate Prorocentrum lima. BullJapan Soc Sci Fish 48(1), 69-72. 

Norte, M., Padilla, A., Fernandez, XX, and Souto, M.L. 1994. Structural determination and biosynthetic origin of two ester derivatives of okadaic acid isolated from Prorocentrum lima. Tetrahedron 50(30), 9175-9180. 

Suzuki, T, Beuzenberg, V, Mackenzie, L., and Quilliam, M. A. 2004. Discovery of okadaic acid esters in the toxic dinofiagel-late Dinophysis acuta from New Zealand using liquid chromatography/tandem mass spectrometry. Rapi Commun Mass Spectrom 18, 1131-1138. 

Takai, A., Murata, M., Torigoe, K., Isobe, M., Mieskes, G., and Yasumoto, T. 1992. Inhibitory effect of okadaic acid derivatives on protein phosphatases. Biochem J 284, 539-544. 

Vale, E, and Sampayo, M.A.M. 1999. Esters of okadaic acid and dinophysistoxin-2 in Portuguese bivalves related to human poisonings. Toxicon 37(8), 1109—1121. 

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