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The importance of ciguatoxins (CTXs) in seafood safety and their emerging occurrence in locations far away from tropical areas highlight the need for simple and low-cost methods for the sensitive and rapid detection of these potent marine toxins to protect seafood consumers. Herein, an electrochemical immunosensor for the detection of CTXs is presented. A sandwich configuration is proposed, using magnetic beads (MBs) as immobilization supports for two capture antibodies, with their combination facilitating the detection of CTX1B, CTX3C, 54-deoxyCTX1B, and 51-hydroxyCTX3C. PolyHRP-streptavidin is used for the detection of the biotinylated detector antibody. Experimental conditions are first optimized using colorimetry, and these conditions are subsequently used for electrochemical detection on electrode arrays. Limits of detection at the pg/mL level are achieved for CTX1B and 51-hydroxyCTX3C. The applicability of the immunosensor to the analysis of fish samples is demonstrated, attaining detection of CTX1B at contents as low as 0.01 μg/kg and providing results in correlation with those obtained using mouse bioassay (MBA) and cell-based assay (CBA), and confirmed by liquid chromatography coupled to high-resolution mass spectrometry (LC-ESI-HRMS). This user-friendly bioanalytical tool for the rapid detection of CTXs can be used to mitigate ciguatera risk and contribute to the protection of consumer health.

Ciguatoxins, the principal causative toxins of ciguatera seafood poisoning, are large ladder-like polycyclic ethers. We report a highly stereoselective 6-exo radical cyclization/ring-closing olefin metathesis sequence to construct the syn/trans-fused polyether system. The new method was applied to the practical synthesis of ciguatoxin CTX3C.

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Zoanthenol, isolated from Zoanthus sp., possesses an extremely complex architecture including contiguous quaternary carbons. An enantioselective synthesis of the fully functionalized ABC‐ring of zoanthenol has been achieved and is described herein. The key features of the synthesis are the enzymatic kinetic optical resolution and the Mizoroki–Heck/Simmons–Smith reaction strategy used to construct the congested asymmetric quaternary carbons.

Maduropeptin, an extremely potent antitumor agent, consists of a 1:1 complex of a carrier protein and a chromophore. We report herein a general and efficient route for the synthesis of the highly strained bicyclo[7.3.0]dodecadiyne core of the chromophore. The key feature of the synthetic strategy is the use of two Sonogashira coupling reactions in a stepwise manner to construct the conjugated dienyne substructure of the fused‐ring system, including the Zalkene at C4,C13.

Ciguatoxins, principal causative toxins of ciguatera seafood poisoning, are large ladderlike polycyclic ethers. Here, we report two convergent routes to synthesis of the multiolefinic left half of ciguatoxins based on a newly developed acyl radical strategy. Remarkably, only 13 steps from the monocyclic E-ring were required to construct the left wing.

A new convergent strategy for assembling 6/6- and 6/7-fused ether ring systems was developed. The key features in our method include Ag-promoted facile formation of chemically labile enol ether from O,S-acetal and addition of an acyl radical to unactivated enol ether to cyclize a six- or seven-membered ether ring.

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An enantioselective synthesis of an epoxybicyclo[7.3.0]dodecenediyne core system of the neocarzinostatin chromophore has been achieved via intramolecular acetylide addition and palladium-mediated coupling of iodocyclopentene 5with alkyne 6. The key cyclopentene moiety, trans-4,5-dihydroxy-2-cyclopenten-1-one 7, was conveniently prepared in both enantiomerically pure forms via enzymatic desymmetrization of meso-3,4,5-trans,trans-trihydroxycyclopentene derivatives.

C-1027 is one of the most potent antitumor antibiotic chromoproteins, and is a 1:1 complex of an enediyne chromophore having DNA-cleaving ability and a carrier apoprotein. The three-dimensional solution structures of the 110 residue (10.5 kDa) C-1027 apoprotein and its complex with the aromatized chromophore have been determined separately by homonuclear two-dimensional nuclear magnetic resonance methods. The apoprotein is mainly composed of three antiparallel β-sheets: four-stranded β-sheet (43–45, 52–54; 30–38; 92–94; 104–106), three-stranded β-sheet (4–6; 17–22; 61–66), and two-stranded β-sheet (70–72; 83–85). The overall structure of the apoprotein is very similar to those of other chromoprotein apoproteins, such as neocarzinostatin and kedarcidin. A hydrophobic pocket with approximate dimensions of 14 A˚ × 12 A˚ × 8 A˚ is formed by the four-stranded β-sheet and the three loops (39–42; 75–79; 97–100). The holoprotein (complex form with the aromatized chromophore) structure reveals that the aromatized chromophore is bound to the hydrophobic pocket found in the apoprotein. The benzodihydropentalene core of the chromophore is located in the center of the pocket and other substituents (β-tyrosine, benzoxazine, and aminosugar moieties) are arranged around the core. Major binding interactions between the apoprotein and the chromophore are likely the hydrophobic contacts between the core of the chromophore and the hydrophobic side-chains of the pocket-forming residues, which is supplemented by salt bridges and/or hydrogen bonds. Based on the holoprotein structure, we propose possible mechanisms for the stabilization and the release of chromophore by the apoprotein.

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The marine antibiotic korormicin, isolated from the culture filtrate of marine bacterial strain Pseudoalteromonassp. F-420, specifically inhibits the growth of marine Gram-negative bacteria without affecting terrestrial species. The absolute configuration of korormicin was determined by the combination of a CD exciton chirality method and chemical degradation. Convergent total synthesis of koromicin has been also achieved.

The rate-limiting step in the Bergman reaction was changed from cyclization to hydrogen-abstraction by benzannelation. This effect should be attributed to the faster rate of the retro-Bergman cyclization and/or the slower rate of hydrogen abstraction by the aromatic ring condensed 1,4-didehydrobenzene intermediate.

The ansamacrolide moiety of kedarcidin has been constructed with complete atropselectivity via intramolecular Sonogashira coupling.

The AB-ring fragment of ciguatoxin was synthesized in ten steps from tri- O-benzyl- d-glucal based on a highly diastereoselective ring-closing metathesis and subsequent cross metathesis.

An efficient and practical synthesis of mycarose and kedarosamine derivatives has been devised from ethyl ( S)-lactate viaa versatile ( E)-alkene intermediate. Noteworthy transformations include a highly trans-selective one-pot Julia olefination protocol and intramolecular cyclisation of a 2,3-epoxy carbamate.

Chiral recognition of 1,12-dimethylbenzo[c]phenanthrene-5,8-dicarboxylic acid (1) by native β- (β-CD) and γ-cyclodextrins (γ-CD) has been studied by means of 1H NMR spectroscopy. The binding constant (K ) for complexation of (M )-1 with β-CD (18700 4;± 4;1700 dm3 mol–1) is much larger than that for (P )-1 (2200 4;± 4;100 dm3 mol–1), ΔΔG being 5.2 kJ mol–1. γ-CD forms less stable inclusion complexes (K 4;= 4;3100 4;± 4;100 and 690 4;± 4;20 dm3 mol–1 for (M )-1 and (P )-1, respectively). The 2D ROESY spectra indicate that both CO2– groups of 1 are placed near the rim of the secondary OH group side of β-CD though the (P )-1 molecule penetrates into the host cavity somewhat more deeply than the (M )-1 molecule. The deeper penetration of the (P )-1 molecule seems to be an enthalpically unfavourable but entropically favourable process because such a complexation needs dehydration from the CO2– group(s) of 1. The enantioselectivity of β-CD toward 1 is dominated by the difference in the enthalpy changes due to the difference in the extent of penetration between the enantiomers of 1. The 2D NMR spectra clearly indicate that at least one CO2– group of 1 is located inside of the γ-CD cavity resulting in extensive dehydration from the guest molecule. Such an endothermic process reduces the K value for the 1-γ-CD complex. The difference in the structures of the complexes between the guest enantiomers might be ascribed to the chiral helix-structure of the CD taken upon complexation in water.

Coupling of the azatyrosine fragment with the cyclopentadiene monoepoxide derivative corresponding to the core moiety of the kedarcidin chromophore has been effectively achieved using CsF.

A stereoselective and concise route to the bicyclo[7.3.0]dodecadiyne core moiety ( 26) of the C-1027 chromophore ( 1) through highly efficient LiN(TMS) 2CeCl 3-mediated cyclization of alkynyl aldehyde 24has been established.

The absolute configuration of C-1027 chromophore was determined as 8 R, 9 R, 13 R, and 18 Susing the modified Mosher's, two-dimensional NMR, and molecular modeling methods.

A reagent system of 1-alkyne, SnCl4, and Bu3N alkynylates aldehydes, acetals, and enones under mild reaction conditions giving acetylenic alcohols, acetylenic ethers, and acetylenic ketones, respectively, in high yields. Alkynyltrichlorotins are shown to be the reactive species for these reactions.

Remarkable kinetic solvent isotope effect, experimental activation energy (15.1 kcal/mol) as well as MO calculations present a reaction energy diagram for cycloaromatization reaction of C-1027 chromophore, a highly strained 1,5-diyn-3-ene molecule.

Easy access to pentane-1,3,5-triol derivatives of high optical purity, trifunctional chiral synthons of fundamental importance in the synthesis of various natural products is described, as well as the stereocontrol of baker’s yeast reduction of 5-substituted 3-oxopentanoates.

Ozonization of benzyl ethers at low temperature in acetone or methanol solvent smoothly gave the corresponding benzoates in good yields.

Thiele type acylation reaction of p-tropoquinone 1, a novel nonbenzenoid quinone, in the presence of sulfuric acid, resulted in the unexpected ring contraction to a benzaldehyde derivative 2, in addition to a tropone 3. It was proved in this reaction that acetoxyl group attacked C3exclusively and that the carbon became aldehydic. In the reaction catalyzed by BF3, regioselectivity of the nucleophilic attack was reduced to 4:1 (C3:C4) yielding 9, 10, and 11, all seven-membered ring compounds. Plausible mechanisms for the all reaction pathways are proposed.

Various reactions were carried out with o-tropoquinone and its hydrate and hemiacetal in order to compare their behavior with that of o-benzoquinone and cyclic vicinal triketones. Although many reactions went parallel with the reference compounds, some abnormal reactions, such as reduction to 3-hydroxytropolone under various conditions, change in the reaction mode in Thiele type acetylation depending on the acid concentration and aromatization by BF3, were observed.

The title compound, a benzolog of o-tropoquinone, was synthesized by the DDQ oxidation of the corresponding hydroxytropolone. Effect of benzene annelation on the physical properties (UV, PMR, CMR, electron affinity) of o-tropoquinone was evaluated. The annelation causes more modification to o-tropoquinone than to o-benzoquinone. This may be due to the reduced planarity of 7-membered quinone ring in the title compound. Easy reduction by HCl and facile BF3-induced aromatization to 1,2-dihydroxynaphthalene were observed.

Cross-conjugated 5-methylene-3-heptene-1,6-diyne derivatives have been proved to be readily epoxidized by molecular oxygen.

An adduct formed from 2-trichlorostannyl-3-pentanone and phenylethynyltrichlorotin was isolated, and the structure was determined by spectroscopy and X-ray crystallography. It provides a direct evidence for the carbostannylation of alkynyl metals.

Selective monodesilylation of 1,8-bis(t-butyldiphenylsilyl)-1,3,5,7-octatetrayne and 1,6-bis(t-butyldiphenylsilyl)-1,3,5-hexatriyne with lithiated phenylacetylene gave unstable 1-(t-butyldiphenylsilyl)-1,3,5,7-octatetrayne and 1-(t-butyldiphenylsilyl)-1,3,5-hexatriyne, respectively. The terminal acetylenes on lithiation added to aldehydes and a ketone giving polyynols in high yields. The reaction was applied to the synthesis of polyyne antibiotics, caryoynencins. Polymerization of the terminal octatetrayne on an ITO-coated glass plate gave a film, which showed conductivity of 10-4S cm-1when doped with SO3.

A concise total synthesis of the 11-membered cyclic (+)-aspercyclide C is reported. Key to success was the fine-tuning of the reaction media to realize an oxidative, macrocyclic diaryl C–O bond formation in a regioselective and direct fashion.

The total synthesis of gravicycle, isolated from Grevillea robusta, has been achieved for the first time. The key step of our synthetic process is the efficient assembly of a highly functionalized biaryl ether via the copper-catalyzed O-arylation of suitably protected pyrogallol-5-carboxylate, using triarylbismuth(V) diacetate.

Lycodine is a representative Lycopodiumalkaloid, which features a bicyclo[3.3.1]nonane core and pyridine and piperidine rings. Stereoselective total synthesis of lycodine was achieved using Diels–Alder and intramolecular Mizoroki–Heck reactions.