Synthesis and two-electron redox behavior of diazuleno[2,1-a:1,2-c]naphthalenes

The Diels-Alder reaction of di-2-azulenylacetylene with tetraphenylcyclopentadienone afforded 7,8,9,10-tetraphenyldiazuleno[2,1-a:1,2-c]naphthalene in one pot via autoxidation of the presumed 1,2-di-2-azulenylbenzene derivative. In contrast, a similar reaction of bis(1-methoxycarbonyl-2-azulenyl)acetylene with tetraphenylcyclopentadienone gave the 1,2-di-2-azulenylbenzene derivative. The following cyclodehydrogenation reaction of the benzene derivative with iron(III) chloride afforded diazuleno[2,1-a:1,2-c]naphthalene 6,11-bismethoxycarbonyl derivative. The redox behavior of these novel diazuleno[2,1-a:1,2-c]naphthalenes was examined by cyclic voltammetry (CV). These compounds exhibited two-step oxidation waves at +0.22 to +0.71 V upon CV, which revealed the formation of a radical cation and dication stabilized by the fused two azulene rings under the electrochemical oxidation conditions. Since the 1,2-di-2-azulenylbenzene derivative was oxidized at higher oxidation potentials (+0.83 and +1.86 V), the fusion of the two azulene rings to naphthalene increased electron-donating properties because of the formation of a closed-shell dicationic structure. Formation of the radical cation was characterized by UV-vis spectroscopy under the electrochemical oxidation conditions, although no evidence was obtained for the presumed dication under the conditions of the UV-vis spectroscopy measurement.     

Synthesis of potent beta-secretase inhibitors containing a hydroxyethylamine dipeptide isostere and their structure-activity relationship studies

Several beta-secretase inhibitors were designed based on hydroxyethylamine dipeptide isostere (HDI) structures and were synthesized by a methodology using the aza-Payne rearragement and O,N-acyl transfer reactions to study their structure-activity relationships. Among these pseudopeptides, effective compounds were developed as the first beta-secretase inhibitors containing the HDI transition state mimic with potent enzyme inhibitory activity (IC50 < 100 nM).     

W(CO)5(L)-catalyzed endo-selective cyclization of allenyl silyl enol ethers: an efficient method for the cyclopentene annulation onto alpha,beta-unsaturated ketones

[reaction: see text] Indium-mediated allenylation of alpha,beta-unsaturated ketones in the presence of tert-butyldimethylsilyl triflate and dimethyl sulfide gives 6-siloxy-1,2,5-trienes, which undergo W(CO)(5)(L)-catalyzed 5-endo cyclization to give the corresponding cyclopentene derivatives in good yield. Furthermore, this novel W(CO)(5)(L)-catalyzed cyclization of allenyl silyl enol ethers proceeds in a 6-endo manner when 5-siloxy-1,2,5-trienes are employed as a substrate. In these reactions, effective electrophilic activation of allenyl compounds for attack by silyl enol ethers is achieved using a catalytic amount of W(CO)(6).     

Convergent synthesis of the A-F ring segment of yessotoxin and adriatoxin

A convergent synthesis of the A-F ring segment of yessotoxin and adriatoxin was achieved via the intramolecular allylation of an α-chloroacetoxy ether and subsequent ring-closing metathesis.     

Substoichiometric radioactivation analysis for ytterbium

The substoichiometric separation of Yb(III) can be achieved by the extraction of a substoichiometric amount of thenoyltrifluoroacetone and an excess amount of phenanthroline in benzene. The appropriate pH range for the substoichiometric extraction is 6–8. The reproducibility of the substoichiometric extraction of Yb(III) is very good as RSD 1%. As an example, Yb in a manganese nodule is determined by the substoichiometry combined with the radioactivation analysis. The content of Yb is 17.63±0.23 g/g. The present procedure can be applied to the determination of other rare earth elements.     

Total Biosynthesis of Melleolides from Basidiomycota Fungi: Mechanistic Analysis of the Multifunctional GMC Oxidase Mld7

Mushroom terpenoids are biologically and chemically diverse fungal metabolites. Among them, melleolides are representative sesquiterpenoids with a characteristic protoilludane skeleton. In this study, we applied a recently established hot spot knock-in method to elucidate the biosynthetic pathway leading to 1α-hydroxymelleolide. The biosynthesis of the sesquiterpene core involves the cytochrome P450 catalyzing stepwise hydroxylation of the Δ⁶-protoilludene framework and a stereochemical inversion process at the C5 position catalyzed by short-chain dehydrogenase/reductase family proteins. The highlight of the biosynthesis is that the flavoprotein Mld7 catalyzes an oxidation-triggered double-bond shift accompanying dehydration and acyl-group-assisted substitution with two different nucleophiles at the C6 position to afford the Δ⁷-protoilludene derivatives, such as melleolide and armillarivin. The complex reaction mechanism was proposed by DFT calculations. Of particular importance is that product distribution is regulated by interaction with the cell membrane.     

Analysis of plasma catecholamines by high-performance liquid chromatography with fluorescence detection: simple sample preparation for pre-column fluorescence derivatization

Analysis of plasma catecholamines (norepinephrine, epinephrine and dopamine) by high-performance liquid chromatography using 1,2-diphenylethylenediamine as a fluorescent reagent is described. We have developed an automatic catecholamine analyser, based on pre-column fluorescence derivatization and column switching. The analysis time for one assay was 15 min. The correlation coefficients of the linear regression equations were greater than 0.9996 in the range 10-10,000 pg/ml. The detection limit, at a signal-to-noise ratio of 3, was 2 pg/ml for dopamine. A new method of sample preparation for the pre-column fluorescence derivatization of plasma catecholamines was used. In order to protect the catecholamines from decomposition, an ion-pair complex between boric acid and the diol group in the catecholamine was formed at a weakly alkaline pH. The stabilities of plasma catecholamines were evaluated at several temperatures. After complex formation, the catecholamines were very stable at 17 degrees C for 8 h, and the coefficients of variation for norepinephrine, epinephrine and dopamine were 1.2, 4.2 and 9.3%, respectively.     

Mediated amperometric biosensor for hypoxanthine based on a hydroxymethylferrocene-modified carbon paste electrode

An amperometric enzyme electrode for the determination of hypoxanthine in fish meat is described. The hypoxanthine sensor was prepared from xanthine oxidase immobilized by covalent binding to cellulose triacetate and a carbon paste electrode containing hydroxymethylferrocene. The xanthine oxidase membrane was retained behind a dialysis membrane at a carbon paste electrode. The sensor showed a current response to hypoxanthine due to the bioelectrocatalytic oxidation of hypoxanthine, in which hydroxymethyiferrocene served as an electron-transfer mediator. The limit of detection is 6 × 10^?7 M, the relative standard deviation is 2.8% (n=28) and the response is linear up to 7 × 10^?4 M. The sensor responded rapidly to a low hypoxanthine concentration (7 × 10^?4 M), the steady-state current response being achieved in less than 1 min, and was stable for more than 30 days at 5 ° C. Results for tuna samples showed good agreement with the value determined by the conventional method.     

Size-Selective Harvesting of Extracellular Vesicles for Strategic Analyses Towards Tumor Diagnoses

Extracellular vesicles (EV), typified by exosomes or microvesicles, are expected to be effective diagnostic markers for cancers. The sizes of the vesicles range from 20 to 1000 nm, but the size-dependent variations of the contents of EVs are still poorly understood. We succeeded in the size-selective harvesting of the vesicles by utilizing the molecular weight-dependent characteristics of a variety of polyethylene glycols (PEG) as precipitating reagents and analyzed the antigens displayed on the surfaces of the vesicles and the miRNAs included in the vesicles from each size group. As a result, the relatively larger (<100 nm) particles precipitated by PEG5k clearly exhibited the greatest amount of epithelial cell adhesion molecule (EpCAM), from both breast cancer (MCF-7) and colon cancer (HCT116) cells, and a larger quantity of microRNA (miRNA) specific to breast cancer cells (miRNA155 for MCF-7) seemed to be contained in the PEG-precipitated particles. The results demonstrated that the quantities of both the tumor-specific miRNA and protein were similarly distributed among the several classes of the size-sorted EVs and that the size-selective harvesting of EVs may be informative for strategic analyses towards the diagnoses of cancers.     

The First Study on the Reactivity of Water Vapor in Metal–Organic Frameworks with Platinum Nanocrystals

We first studied the reactivity of H₂O vapor in metal–organic frameworks (MOFs) with Pt nanocrystals (NCs) through the water–gas shift (WGS) reaction. A water‐stable MOF, UiO‐66, serves as a highly effective support material for the WGS reaction compared with ZrO₂. The origin of the high catalytic performance was investigated using in situ IR spectroscopy. In addition, from a comparison of the catalytic activities of Pt on UiO‐66, where Pt NCs are located on the surface of UiO‐66 and Pt@UiO‐66, where Pt NCs are coated with UiO‐66, we found that the competitive effects of H₂O condensation and diffusion in the UiO‐66 play important roles in the catalytic activity of Pt NCs. A thinner UiO‐66 coating further enhanced the WGS reaction activity of Pt NCs by minimizing the negative effect of slow H₂O diffusion in UiO‐66.