Concise Construction of the ACDE Ring System of Calyciphylline A Type Alkaloids by a [5+2] Cycloaddition

A concise route for construction of the ACDE ring skeleton in calyciphylline A type alkaloids was developed using an intramolecular [5+2] cycloaddition reaction of an oxidopyrylium species bearing a tetrasubstituted olefin. Key to the success of this reaction was the combination of acid and base, which accelerated the construction of this skeleton containing a spiro ring and vicinal quaternary carbon centers. The resultant tricyclic ADE ring compound was converted to an ACDE ring model through C−H oxidation and an aza-Wittig reaction.     

Simultaneous Induction of Axial and Planar Chirality in Arene–Chromium Complexes by Molybdenum‐Catalyzed Enantioselective Ring‐Closing Metathesis

The molybdenum‐catalyzed asymmetric ring‐closing metathesis of the various C_s‐symmetric (π‐arene)chromium substrates provides the corresponding bridged planar‐chiral (π‐arene)chromium complexes in excellent yields with up to >99 % ee. With a bulky and unsymmetrical substituent, such as N‐indolyl or 1‐naphthyl, at the 2‐positions of the η⁶‐1,3‐diisopropenylbenzene ligands, both biaryl‐based axial chirality and π‐arene‐based planar chirality are simultaneously induced in the products. The axial chirality is retained even after the removal of the dicarbonylchromium fragment, and the chiral biaryl/heterobiaryl compounds are obtained with complete retention of the enantiopurity.     

Synthesis and Chiroptical Properties of Chiral Carbazole-Based BODIPYs

A series of carbazole-based boron dipyrromethenes (BODIPYs) 2 a – g bearing binaphthyl units have been synthesized by the Et₂AlCl-mediated reaction of the corresponding BODIPY difluorides 1 a – g with 1,1′-binaphthalene-2,2′-diol. Substituents such as halogen, nitrile, and amino groups were tolerated under the reaction conditions, and the reaction of the phenylethynyl-substituted 1 h gave (R,R)- 3 h bearing two binaphthyl units. The chiroptical properties of these dyes with different substituents were investigated by UV/Vis, CD, fluorescence, and circularly polarized luminescence (CPL) spectroscopy. The CD spectra showed Cotton effects in the absorption region of the BODIPY moieties. In addition, they showed CPL both in solution and in the solid state. Interestingly, several dyes recorded higher g_lum values in the solid state, probably due to intermolecular interactions. Because (R,R)- 3 h recorded relatively low g_lum values, the diastereomer (R,S)- 3 h was prepared. The (R,S) diastereomer showed intense CPL, which suggests a synergetic effect of the two binaphthyl groups. Finally, chiral carbazole-based BODIPY dimers have been synthesized for the first time and their chiroptical properties were investigated. They showed redshifted fluorescence and CPL, which reached the near-IR (NIR) region in the solid state.     

A high‐performance liquid chromatography assay with a triazole‐bonded column for evaluation of d‐amino acid oxidase activity

Elution profiles of kynurenic acid (KYNA) and 7‐chlorokynurenic acid (Cl‐KYNA) were examined by high‐performance liquid chromatography (HPLC) using a triazole‐bonded stationary phase column (Cosmosil® HILIC) under isocratic elution of a mobile phase consisting of CH₃CN–aqueous 10 mm ammonium formate between pH 3.0 and 6.0. The capacity factors of KYNA and Cl‐KYNA varied with both the CH₃CN content and the pH of the mobile phase. The elution order of KYNA and Cl‐KYNA was reversed between the CH₃CN‐ and H₂O‐rich mobile phases, suggesting that hydrophilic interactions and anion‐exchange interactions caused retention of KYNA and Cl‐KYNA in the CH₃CN‐ and H₂O‐rich mobile phases, respectively. The present HPLC method using a triazole‐bonded column and fluorescence detection (excitation 250 nm, emission 398 nm) was applied to monitor in vitro production of KYNA from d ‐kynurenine (d ‐KYN) by d ‐amino acid oxidase (DAO) using Cl‐KYNA as an internal standard. A single KYNA peak was clearly observed after enzymatic reaction of d ‐KYN with DAO. Production of KYNA from d ‐KYN was suppressed by the addition of commercial DAO inhibitors. The present HPLC method can be used to evaluate DAO activity and DAO inhibitory effects in candidate drugs for the treatment of schizophrenia. Copyright © 2015 John Wiley & Sons, Ltd.     

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.     

Preparation of Molecule‐Responsive Microsized Hydrogels via Photopolymerization for Smart Microchannel Microvalves

Microdevices designed for practical environmental pollution monitoring need to detect specific pollutants such as dioxins. Bisphenol A (BPA) has been widely used as a monomer for the synthesis of polycarbonate and epoxy resins. However, the recent discovery of its high potential ability to disrupt human endocrine systems has made the development of smart systems and microdevices for its detection and removal necessary. Molecule‐responsive microsized hydrogels with β‐cycrodextrin (β‐CD) as ligands are prepared by photopolymerization using a fluorescence microscope. The molecule‐responsive micro‐hydrogels show ultra‐quick shrinkage in response to target BPA. Furthermore, the flow rate of a microchannel is autonomously regulated by the molecule‐responsive shrinking of their hydrogels as smart microvalves.

     

Accurate intensity calibration for low wavenumber (−150 to 150 cm−1) Raman spectroscopy using the pure rotational spectrum of N2

We report on an accurate intensity calibration method for low wavenumber Raman spectroscopy. It uses the rotational Raman spectrum of N₂. The intensity distributions in the rotational Raman spectra of diatomic molecules are theoretically well established. They can be used as primary intensity standards for intensity calibration. The intensity ratios of the Stokes and anti‐Stokes transitions originating from the same rotational levels are not affected by thermal population. Taking the effect of rotation–vibration interactions appropriately into account, we are able to calculate these intensity ratios theoretically. The comparison between the observed and calculated ratios of the N₂ pure rotational spectrum provides an accurate relative sensitivity curve (error ~5 × 10⁻⁴) in the wavenumber region of −150 to 150 cm⁻¹. We determine the temperature of water solely from the low wavenumber Raman spectra, using a thus calibrated spectrometer. The Raman temperature shows an excellent agreement with the thermocouple temperature, with only 0.5 K difference. The present calibration technique will be highly useful in many applications of low wavenumber quantitative Raman spectroscopy. Copyright © 2015 John Wiley & Sons, Ltd.