Ichthyotoxicity

A particularly flexible and novel entry into prostaglandins and analogs, either by RCAM (463—>464) or by the intermolecular variant ACM (462+466 -+467) from a common intermediate (462), is outlined in Scheme 93 [190]. Prostaglandin E2-1,15-lactone (465), an ichthyotoxic compound produced by a marine nudibranch for defense purposes, was produced in Fiirstner s laboratory along the RCAM-based sequence 462 463—>464-+465. Alternatively, the... 

Sea cucumbers (Holothurioidea) contain highly toxic saponins which presumably play a role in protection since the relatively unprotected bodies of these species make them particularly vulnerable to predation. When "attacked", a sea cucumber expels Cuverian glands whose projections elongate and enmesh an assailant while, at the same time, exuding ichthyotoxic saponins to discourage further attacks. Some 30 species of sea cucumbers contain saponins which are highly toxic to other marine creatures as well as fish. 

Indium-mediated allylation of an unreactive halide with an aldehyde132 was used to synthesize an advanced intermediate in the synthesis of antillatoxin,133 a marine cyanobacteria (Lyngbya majus-cula) that is one of the most ichthyotoxic compounds isolated from a marine plant to date. In the presence of a lanthanide triflate, the indium-mediated allylation of Z-2-bromocrotyl chloride and aldehyde in saturated NH4C1 under sonication yielded the desired advanced intermediate as a 1 1 mixture of diastereomers in 70% yield. Loh et al.134 then changed the halide compound to methyl (Z)-2-(bromomethyl)-2-butenoate and coupled it with aldehyde under the same conditions to yield the desired homoallylic alcohol in 80% yield with a high 93 7 syn anti selectivity (Eq. 8.55). 

Malaysia, the seeds are poisonous and used to catch fish. The plant has not been studied for its pharmacological potentials. The ichthyotoxic property could involve some naphthoquinones and/or saponins. 

With the isolation of both 9-isocyanopupukeanane (76) and its epimer (77) from P. bourguini, coupled with the results of ichthyotoxicity assays, the suggestion was made that the origin of these compounds may not be exclusively dietary i.e., partial metabolism of 76 to 77 by the nudibranch may be operative [56]. 

In the search for bioactive marine secondary metabolites, drugs or drug leads with new modes of action, many invertebrates with new modes of action have been explored and tested in a variety of assays. Many marine natural products were found to be cytotoxic to an assortment of tumor cells, Some parts of the marine natural products were also found to be ichthyotoxic so as to defend themselves. Two examples, out of many, are the latrunculins and sarcophine. ... 

Okuda RK, Scheuer PJ, Latruncidin-A, ichthyotoxic constituent of the nudi-... 

Rao KV, Davies R, The ichthyotoxic principles of Zanthoxylum clava-herculis, J Nat Prod AS-MO-Hl, 1986. 

Most marine biotoxications are caused by fishes, but turtles and mammals have been incriminated in rare instances. A tentative classification of ichthyotoxic fishes is as follows ... 

The mangrove plant Heritiera littoralis (Stercullaceae) has been utlized by natives of the Philippines as a fish poison. The hexane extract of this plant has shown toxicity to fish (Tilapia nllotlca). A novel sesquiterpene which was assigned the name heritianin has been identified as one of the compounds with ichthyotoxicity. The structure elucidation of heritianin and other compounds in the hexane extract of Heritiera littoralis is presented with bioassay data. 

Capon, R.J. Faulkna, D.J. (1985) Habasterol, an ichthyotoxic 9,11-secostaol from the sponge Dysidea herbacea. J. Org. Chem., 50,4771-3. 

Igarashi, T. Satake, M. Yasumoto, T. (1999) Structures and partial stereochemical assignments for prymnesin-1 and prymnesin-2 potent hemolytic and ichthyotoxic glycosides isolated from the red tide alga Prymnesium parvum. J. Am. Chem. Soc., 121, 8499-511. 

Izac, R.R. Poet, S. Fenical, W. van Engen, D. Clardy, J. (1982) The structure of pacifigorgiol, an ichthyotoxic sesquiterpenoid from the Pacific gorgonian coral Pacifigorgia cf. adamsi. Tetrahedron Lett., 23, 3743-6. 

The ichthyotoxic diacylglycerol umbraculumin C (203) was isolated from the Mediterranean ophistobranch Umbraculum mediterraneum [206], The stereochemistry of compound 203 was determined by chemical interconversion and total synthesis [207]. 

Halistanol sulfate (532) from Halichondria cf. moorei is a tris-sodium sulfate salt, which possesses antimicrobial, hemolytic, and ichthyotoxic activity [444]. It was later isolated from two sponges of the genus Topsentia as the free sterol and found to inhibit pp60v-src protein tyrosine kinase activity [445]. The tris(2-aminoimidazolium) salt of halistanol sulfate (533) was isolated from Topsentia sp. from Japan and is also antimicrobial [446]. 

An Acanthodendrilla sp. from Japan contained ten steroidal sulfates, acanthosterol sulfates A-J (561-570). Acanthosterol sulfates I (569) and J (570) showed antifungal activity against Saccharomyces cervisiae and its mutants [463]. Clathsterol (571), was isolated from the Red Sea sponge Clathria sp. The structure was established mainly by interpretation of spectral data and a chemical transformation. Clathsterol (571) was active against HIV-1 reverse transcriptase (RT) at a concentration of 10 iM [464]. Toxadocia zumi contains three sterol sulfates (572-574) that are antimicrobial, cytotoxic, ichthyotoxic and larvicidal [465]. 

Tremetone (17) seems also to have insecticidal properties 27,30a,1> similar to those of rotenone (13)31 (and half its ichthyotoxic action). It should be noticed that the structure of tremetone is similar to rings C, D, and E of rotenone. 

Deguelin (19),32 in which rings D and E have a chromene, not a benzofuran, structure, is fully as ichthyotoxic and insecticidal as rotenone. It has been suggested33 that the toxophore in rotenoids might be the sequence =CH—CH=CH—O— in rings C and D, which is found both in (13) and in (19). The same sequence is found in... 

The red tide alga Prymnesium parvum poses a serious threat to fish farming. Prymnesin-2 (184) (CggHnsC NC ), the major toxin of the phytoflagellate, shows potent hemolytic and ichthyotoxic properties. The minimum concentration to cause hemolysis of a 1% mouse blood cell suspension and to kill fresh water fish, Tanichthys albonubes, is 3 nM [145]. 

Umbraculumin C (90), characterized by the presence of a trans-3-(methylthio)-acrylic acyl residue, is a diacylglycerol obtained from the skin of the opisthobranch mollusc Umbraculum mediterraneum [96]. Taylor and co-workers determined the absolute configuration of 90 by total synthesis [97] while Sodano et al. reached the same conclusion by derivatisation of the natural compound [98]. Compound 90 displayed ichthyotoxic activity against the mosquito fish at 0.1 pg/ml and should represent the deterrent of this organism against predators [96]. 

The Japanese sponge Discodermia calyx has yielded the new calyculin, calyculin J (1669) (1631). The highly toxic (ichthyotoxicity, hemolytic activity) prymnesin-1 (1670) and -2 (1671), possessing unprecedented structural complexity, were characterized from the red tide alga Prymnesium parvum (1632-1634). 

IgarashiT, SatakeM, YasumotoT (1996)Prymnesin-2 A Potent Ichthyotoxic and Hemolytic Glycoside Isolated from the Red Tide Alga Prymnesium parvum. J Am Chem Soc 118 479... 

As a result, a large number of secondary metabolites have been described from various species of algae. Just the two best-studied groups, the red algal genus Laurencia and the brown algal family Dictyotaceae, account for more than 500 compounds. Many of these compounds are known to be cytotoxic, ichthyotoxic, or antimicrobial. 

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