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Ciguatera fish poisoning (CFP) is a human foodborne intoxication caused by ingestion of tropical fishes contaminated with the potent polyether toxins known as ciguatoxins (CTXs). These toxins are issued from Gambierdiscus species of dinoflagellates. Herbivorous fish accumulate these toxins in their musculature and viscera 'after ingesting dinoflagellates. Epidemiological studies showed that CFP has been present in areas between 35[degrees] North and 35[degrees] South latitude, mainly, Indo-pacific and Caribbean areas, but not in waters closed to European and African continent. In the present paper, a specimen of Serlola dumerili weighing 70 kg and a smaller Seriola fasciata specimen, captured in waters belonging to Selvagens Islands (Madeira Arquipelago), were analyzed. Fishes from this genus were implicated in previous suspected ciguatera poisoning outbreaks in the Portuguese Madeira Arquipelago in the North Atlantic Ocean. Analysis was performed by two approaches, a functional method using cerebellar granule cells and by ultra-performance liquid chromatography mass spectrometry (UPLCMS) method. The study was carried out in one portion of the tail muscle of Seriola fasciata and five parts of the body of Seriola dumerili (tail muscle, head, ventral muscle, mid muscle, and liver). The functional method consisted in the modification of the inward sodium current in cerebellar granule cells and the chemical method was a high resolution chromatography, which allowed elucidating the toxin profile in the samples. In addition, UPLC-MS technique was optimized and used for detecting and quantifying CTXs for the first time. After fish extraction and clean up, the chromatograms revealed the presence of CTX-1B at 1111.6 m/z, CTX-3C at 1023.5 m/z, a CTX analogue at 1040.6 m/z, and a CTX from the Caribbean or Indic waters at 1141.6 m/z. Therefore, the results obtained in the present paper for both methods confirm, for the first time, the presence of CTX in fish from Madeira Arquipelago. 10.1021/ac100516q

The total synthesis of the unnatural enantiomer of merrilactone A is described based on a novel desymmetrization strategy. The natural and unnatural enantiomers of synthetic merrilactone A have equally promoted neurite outgrowth in primary neuronal cultures.

Mechanistic insights into the self-reactivity of C-1027 that facilitates its own decomposition are described. Evidence is provided that the formation of Gly96 radical, which promotes the oxidative protein scission and the subsequent chromophore release, is the major pathway for the self-decomposition of C-1027.

The highly convergent total synthesis of CTX3C is improved and refined to a satisfactory level in terms of overall stereoselectivity and efficiency. The molecules synthesized will accelerate development of strategies to control ciguatera and lead to the creation of voltage-sensitive sodium channels (VSSC) probes that may elucidate VSSC-ligand interactions at the molecular level.

Specific monoclonal antibodies (mAbs) have been prepared against both ends of CTX3C by immunization with protein conjugates of rationally designed synthetic haptens in place of the scarce natural toxins. The haptenic groups required a surface area larger that 400 A(super 2) to induce mAbs which can strongly bind the CTX3C.

A study was conducted to examine the ortho-vinylation reaction of phenols with ethyne. 2-Ethenyl-1,4-benzenediol was synthesized through the deprotection of the diacetate with K2CO3-methanol. Vinylation was also applied to phenols supporting electron-withdrawing groups. Results indicated that ortho and para-substituted phenols supported mono-vinylated products in high yields. Findings also showed that the ortho-substituent did not interfere with vinylation.

Research has been conducted on the chiral (E)-enediyene and (E)-epoxydiyene. The application of the carbometalation methodology to the extended propargylic chiral diol has been carried out in the synthesis of these compounds and the results are reported.

The structure of the maduropeptin chromophore, the biologically active component of the highly potent chrooprotein antitumor antibiotics, is stereoselectively prepared but has not satisfied the spectra of the natural product. The studies have shown that the correct structure is diastereomeric, which has possessed an antipodal sugar moiety.

A new route for the total synthesis of the aglycon of the maduropeptin chromophore is discussed.

The total synthesis of ciguatoxin and 51-hydroxyCTX3C, the two most toxic members of the ciguatoxin family, which is the principal cause for ciguatera seafood poisoning, is described. The synthesis, effected from the corresponding left and right wing fragments in a minimum number of steps, is based on a second generation strategy combined with a stereo- and chemoselective radical cyclization process.

An efficient route to the neocarzinostatin chromophore aglycon is developed, where the present synthesis involves convergent assembly of the functionalized cyclopentenone with the acetylenic fragment, followed by stereocontrolled nine-membered ring closure. The C8-C9-olefin is introduced by using the Martin sulfurane dehydration reaction to furnish the highly reactive aglycon.

The key transformations in the synthesis of the right wings of ciguatoxins are presented. These syntheses improved the stereoselectivity and efficiency in comparison to a previous synthesis.

A supra C-1027 is created by reducing the self-decomposition pathway by means of the kinetic isotope effect. It demonstrated the novel modification of a natural product to acquire superior properties by integrating the physico-chemical properties of the small molecule and the 3D structure of the protein.

Merrilactone A isolated from Illicium merrillianum in 2000, is shown to possess neurotrophic activity in cultures of fetal rat cortical neurons. Merrilactone A is expected to hold therapeutic potential in the treatment of neuro-degeneration associated with Alzheimer's and Parkinson's diseases.

The realization of a concise and efficient strategy that has culminated in the first total synthesis of N1999-A2 and the chemical evidence of a thiol-triggered aromatization of N1999-A2 are described. The results show that the (S)-configured C11-naphthoate unit plays a dominant role in not only controlling the trans-orientation of thiol attack, which triggers aromatization, but also in the efficient recognition and base-specific cleavage of DNA.

The radical species in C-1027 antibiotic was characterized using EPR spectroscopy.

Kedarcidin is a new family of chromoprotein antitumor antibiotic incorporating a cytotoxic nine-membered enediyne chromophore. The structure of the chromophore (1) was described in 1993. A core moiety of ent-1 has been stereoselectively synthesized. The synthesis of the chlorazatyrosyl naphthoamide fragment (2) of ent-1 is described. The fragment degraded from the chromophore was found to be a beta-amino ester, rather than an alpha-amino acid derivative.

It was possible to determine the absolute configurations of ciguatoxin (CTX) and the ciguatoxin precursor CTX4A with very small amounts of toxins when a new chiral fluorescent reagent was used in combination with the CD exciton chirality method. This research has produced stereochemical information that should considerably boost synthetic efforts towards CTX. In the long term, it should be possible to undertake pharmacological, immunological and toxicological studies of ciguatera.

Chromophores may be equilibrated with p-benzyne forms and are stimulated by suitable apoprotein. This equilibrium appears to be reliant to some extant on aromatic amino acids, and the kinetic stabilization appears to be reliant on internal tyrosine and benzoxazine rings a p-benzyne biradical scheme.

Reaction of phenols with ethyne and 1-alkynes in the presence of SnCl4 and Bu3N, under refluxing conditions leads to direct ortho-vinylation and ortho-alkenylation of phenols. Exo-olefins are produced by the reaction of alkynes at the internal carbon atom. Alkenylation in meta-substituted phenols occurs at the less hindered ortho-site. Synthesis of (E)-(beta-(trimethylsilyl))phenols involves the reaction of (trimethylsilyl)acetylene with phenol. Electrophilic characteristics of alkynyltrichlorotins at the beta-carbon atoms account for the regioselective formation of exo-olefin.

The synthesis of a highly strained bicyclo(7.3.0)dodecadiyne system involves LiN(TMS)2/CeCl3-mediated cyclization procedures. These bicyclo(7.3.0)dodecenediyne systems undergo extremely facile Cope rearrangement. NMR studies of the half-life for rearrangement suggest that small structural changes such as shifting of a double bond change the rate of Cope rearrangement. Two prepared diynes have the required functionality to synthesize the antibiotic chromoprotein C-1027 and kedorcidin.

1. Desmosine and isodesmosine were detected in an invertebrate molluscan species, i.e. in an insoluble protein in the hinge ligament of a bivalve species, Sakhalin surf clam (Pseudocardium sachalinensis, in family Mactridae). The protein is rich in glycine and methionine S-oxide but devoid of hydroxyproline and hydroxylysine. 2. 3,3′-Methylenebistyrosine was also detected in the HCl hydrolysate of the hinge-ligament protein, but it was found to be an artefact produced from tyrosine and formaldehyde derived from methionine S-oxide during the HCl hydrolysis of the protein. [ABSTRACT FROM AUTHOR]