Ichthyotoxic compounds

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... 

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). 

CAUTION As with all azides of low molecular weight, tert-butyl azidoformate is sensitive to both heat (>80°C) and shockJ l It is usually purified by distillation under reduced pressure and detonation under these conditions has been reported (distillate and distillation residue are prone to explode). All operations involving this reagent should be carried out with great caution in a fume hood and behind a safety shield Hydrogen azide is an ichthyotoxic compound. 

Higudu, R., Miyamoto, T, Yamada, K., and Komori, T. (1998) Cytotoxic and ichthyotoxic compounds from marine opisthobranchia and soft coral. Toxicon, 36,1703—1705. 

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]. 

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. 

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]. 

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]. 

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. 

From sponges of the genus Jaspis collected at Fiji (300,301), Palau (300), and Papua New Guinea (302), jaspamide (jasplakinolide, 372) was isolated the compound shows potent insecticidal, antifungal, anthelminthic, and ichthyotoxic activity. The structure was determined by X-ray analysis (300). The solution conformation of372 was reported using NMR, molecular mechanics, and dynamics calculations (303). A complexation study was carried out with 372 and the univalent metal ions Li ", Na+, and K+. Li+ binding was observed, and the complex was characterized by NMR and molecular mechanics calculations (304). Jaspamide (372) has potent in... 

During their studies on the stereochemistry of intramolecular 1,3-diyl trapping reaction as depicted in Scheme 13, Little and collaborators utilized the reductive decarboxylation in preparing the required compound 31.24 The usefulness of Barton decarboxylation was also realized by Braekman and colleagues during their studies on ichthyotoxic sesterterpenoids in providing the needed methyl ketone 32 from the carboxylic acid 33.25 Helmchen has developed an easy route to a stable... 

Bioactivity-guided fractionation of organic extracts from two Lyngbya majuscula collections led to the isolation of a new secondary metabolite, antillatoxin B 356, an unusual A -methyl homophenyl-alanine analogue of the potent neurotoxin antillatoxin 357. Compound 356 exhibited significant sodium channel-activating (ECso = 1-77 pM) and ichthyotoxic (LCso = 1 pM) properties. 

The first totai synthesis of the ichthyotoxic marine naturai product (-)-apiyoiide A was accomplished by Y. Stenstrom and co-workers. The compound has a 16-membered lactone ring, four (Z)-double bonds, as well as a stereogenic center. Numerous macroiactonization protocols were tested, but most of them gave the diolide (dimer) except for the Corey-Nicoiaou procedure. 

In 1997, Spinella et al. isolated testudinariol A (149, Figure 6.6) as a metabolite of the marine mollusc Pleurobrancus testudinarius. This compound is a structurally unique triterpene alcohol, and thought to be a defensive allomone of P. testudinarius, because 149 was ichthyotoxic against a fish Gambusia afjinis. The partially cyclized squalene skeleton present in 149 is unique and biosynthetically unusual as in the case of limatulone (148). The unique structure 149 of testudinariol A led us to achieve its synthesis in 2001.8,9... 

Bryophytes are divided into three classes, Musci, Hepaticae (liverwort) and Anthocerotae, which are known to include 14000,6000 and 300 species, respectively. Various kinds of biologically active compounds have been discovered from bryophytes. For instance there are compounds with hot or bitter taste, ichthyotoxicity, insect antifeedant, antiinflammatory, antimicrobial, antifungus and antitumor activities (1). In liverworts, there exist oil bodies, while in Musci, no oil bodies are present. This can help us to identify the liverworts. 

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