Palytoxin analogs from the dinoflagellate Ostreopsis siamensis

Abstract

Palytoxin (1, C129H223N3054, Figure 1) is one of the most potent and complex marine toxins.' Though first isolated from the zoanthid Palythoa toxica, its biogenetic origin was questioned because of marked seasonal and regional variations,2 but the question was never pursued. Sporadic occurrence of palytoxin in an alga,3 crabs," and a herbivorous fish5 also suggested that the toxin might be produced by a microorganism and transmitted to the marine food chain, as is the case with ciguatera, where the epiphytic dinoflagellate Gambierdiscus toxicus produces ciguatoxins and maitotoxin that are isolated from fish.6 Ostreopsis siamensis drew our attention because of its close taxonomical relationship to G. toxicus and the potency of its toxins, named ostre~cins.~ In this Communication, we report the major ostreocin as a palytoxin analog. 0. siamensis (SOA1 strain) was collected at Aka Island, Okinawa, Japan, and grown for 30 days under the same culture conditions as G. toxic~s.'~ Cells harvested by filtration were extracted three times with MeOWH20 (1 : 1) at room temperature and then with MeOH/H20/HOAc (50:50:0.2) under reflux. Purification of ostreocins from the combined extracts was carried out by solvent partition and column chromatography.8 Ostreocins were resolved into five constituents. Purification was monitored by mouse assay following characteristic W maxima. The major constituent, ostreocin D, accounted for 70% of total toxicity. From 936 L of culture, 3.8 mg of ostreocin D was recovered. (2) Moore, R. E.; Helfrich, P.; Patterson, G. M. L. Oceanus 1982, 25, 54-62. (3) Maeda, M.; Kodama, R.; Tanaka, T.; Yoshizumi, H.; Nomoto, K.; Takemoto, T.; Fujita, M. 27th Symposium on the Chemistry of Natural Products; Tanaka, O., Ed.; Symposium papers, Hiroshima, Japan, 1985; Yamawaki Publishing: Hiroshima, 1985; pp 616-623. (4) (a) Yasumoto, T.; Yasumura, D.; Ohizumi, Y.; Takahashi, M.; Alcala, A. C.; Alcala, L. C.(8) The algal extracts were suspended in CHzCl2 and extracted with MeOWH20 (1:l). The aqueous phase, after being concentrated, was extracted with 1-BuOH. The 1-BuOH extract was successively chromatographed on the following columns with solvents as indicated: Toyopearl HW60-fine, MeOWH20 (3:2), Inertsil C8, H20, H20iPrOH (4:1,3:Z); CM Toyopearl 650M. 1% HOAC. The eluates were monitored by mouse assay. Resolution of ostreocins into five constituents and final purification of ostreocin D were achieved on Develosil TMS-5 with H20/CH3CN (3: 1) containing 0.1% HOAc. Eluates were monitored with a Hitachi C-6500 J3D Chromatosystem at 235 and 263 nm. All columns were washed with 10 mM aqueous EDTA-2Na before use. 47, 1029-1033. 0002-7863/95/15 17-5389$09.00/0 on Figure 1. Planar structure of palytoxin (1) and ostreocin D (3,26bisdesmethyldeoxypalytoxin). Bold lines denote connectivities elucidated by DQF-COSY, TOCSY, HSQC, and HMBC data. W chromophores are bracketed.12 Palytoxin, Rl = RZ = Me. Ostreocin D, R1 = Rz = H; O H -H (position not located). Ostreocin D (OST-D) was a colorless amorphous solid: positive to ninhyd...

Putative palytoxin and its new analogue, ovatoxin-a, in Ostreopsis ovata collected along the ligurian coasts during the 2006 toxic outbreak

“…Structure of ostreocin-D was assigned to 42-hydroxy-3,26-didemethyl-19,44-dideoxypalytoxin, based on NMR data [9,10], and verified by negative-ion fast-atom bombardment collision-induced dissociation tandem mass spectrometry [11]. The charge-remote fragmentations were facilitated by a negative charge introduced to the terminal amino group or to a hydroxyl group at the other terminus of the molecule by reaction of pure ostreocin-D with 2-sulfobenzoic acid cyclic anhydride.…”

Toxins of Pufferfish—Distribution, Accumulation Mechanism, and Physiologic Functions

“…Therefore, the causative parrotfish was presumed to have ingested a large amount of Ostreopsis cells with seaweeds, and involvement of Ostreopsis in parrotfish toxification was strongly suspected. Ostreopsis are the benthic dinoflagellates mainly distributed in tropical and subtropical regions (Fukuyo 1981), and one of the species, O. siamensis produces PLTX analogues (Ukena et al 2001;Usami et al 1995). Then, the Ostreopsis sp.…”

Potentiality of benthic dinoflagellate cultures and screening of their bioactivities in Jeju Island, Korea

“…In particular, different types of toxins have been detected in different species of benthic dinoflagellates such as Amphidinium carterae (Haemolysins) (Nakajima et al, 1981;Yasumoto et al, 1987), Prorocentum lima (okaidic acid and dinophysistoxins) (Murakami et al, 1982), Prorocentrum rhathymum (water-soluble fast-acting toxins and hemolytic effects) (Nakajima et al, 1981;Tindall et al 1989), Coolia monotis (cooliatoxin) (Holmes et al, 1995) and Ostreopsis sp. (toxic butanol-soluble compound, palytoxin analogue) (Elbrächter and Faust, 2002;Nakajima et al, 1981;Usami et al, 1995).…”