Biosynthesis of Indole Diterpene Lolitrems: Radical‐Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome‐editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical‐induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.     

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.     

Simple Synthesis of a Heterocyclophane Exhibiting Anti-c-Met Activity by Acting as a Hatch Blocking Access to the Active Site**

A simple approach to the synthesis of heterocyclophane consisting of two 4,4’-bithiazoles has been developed in mild conditions. The heterocyclophane with two short chains was conveniently prepared by Hantzsch thiazoles synthesis using the reaction of 3-tert-butoxycarbonyl-3-azapentanethiocarboxamide with 1,4-dibromobutane-2,3-dione in methanol under reflux for only 15 min. Amino groups at the linkers of this heterocyclophane can be functionalized to give acylated and carbamate derivatives. Their properties as protein kinase inhibitors were investigated, and one of the heterocyclophanes exhibited specific anti-activity for c-mesenchymal epithelial transition factor (IC₅₀=603 nm ), among seven types of protein kinases investigated. The computational site identification by ligand competitive saturation method was used to determine why the one heterocyclophane exhibited strong anti-activity for c-mesenchymal epithelial transition factor.     

Amphiphilic liquid‐crystalline 4‐miktoarm star copolymers with a siloxane junction leading to cylindrically nanostructured templates for a siloxane‐based nanodot array

Well‐defined A₃B‐, A₂B₂‐, and AB₃‐type 4‐miktoarm star copolymers (M_n = 10,500–16,200, M_w/M_n = 1.16–1.18) consisting of poly(ethylene oxide) (PEO) and polymethacrylate bearing an azobenzene mesogen (PMA(Az)) as the arms and cyclotetrasiloxane as the core unit were synthesized using a combined route composed of a thiol‐ene click reaction and atom transfer radical polymerization. Microphase‐separated structures of the star copolymers in thin films with a thickness of approximately 100 nm were investigated by GISAXS and TEM. The A₃B‐type star‐(PEO)₃[PMA(Az)]₁ copolymer formed a more highly ordered PEO cylinder array with perpendicular alignment in the PMA(Az) matrix than that of the corresponding linear‐type block copolymer. The center‐to‐center distance of the PEO cylinders and the cylinder diameter were 13 and 4 nm, respectively. The highly ordered star‐(PEO)₃[PMA(Az)]₁ thin film was directly transferred to a siloxane‐based nanodot array by oxygen reactive ion etching. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1175–1188     

Hydrazine (N2H4) adsorption on Ni(1 0 0) – Density functional theory investigation

A theoretical study on the structure and adsorption mechanism of hydrazine (N₂H₄) on Ni(1 0 0) are presented. The hydrazine molecule was found to adsorb on the surface through one of its nitrogen atom in its anti-conformation. The charge transfer from hydrazine lone pair orbitals played a key role in the formation of the bonding. The mechanism involved in the bonding was found to reduce the necessity of hyper-conjugation interaction, that reduces the gauche effect found in hydrazine at the gas-phase. Upon adsorption to the surface, the reduced interaction resulted in the promotion of a more favored conformation through its anti-conformation.     

Ultraviolet and visible upconversion luminescence of Tm(0.1)Yb(5):FOV oxyfluoride nanophase vitroceramics

The ultraviolet upconversion luminescence of Tm³⁺ ions sensitized by Yb³⁺ ions in oxyfluoride nanophase vitroceramics when excited by a 975 nm diode laser was studied. An ultraviolet upconversion luminescence line positioned at 363.6 nm was found. It was attributed to the fluorescence transition of ¹D₂→³H₆ of Tm³⁺ ion. Several visible upconversion luminescence lines at 450.7 nm, (477.0 nm, 462.5 nm), 648.5 nm, (680.5 nm, 699.5 nm) and (777.2 nm, 800.7 nm) were also found, which result respectively from the fluorescence transitions of ¹D₂→³F₄, ¹G₄→³H₆, ¹G₄→³F₄, ³F₃→³H₆ and ³H₄→³H₆ of Tm³⁺ ion. The careful measurement and analysis of the variation of upconversion luminescence intensity F as a function of the 975 nm pumping laser power P prove that the upconversion luminescence of ¹D₂ state is partly a five-photon upconversion luminescence, and the upconversion luminescence of ¹G₄ state and ³H₄ state are respectively the three-photon and two-photon upconversion luminescence. The theoretical analysis suggested that the upconversion mechanism of the 363.6 nm ¹D₂→³H₆ upconversion luminescence is partly the cross energy transfer of {³H₄(Tm³⁺), ³F₄(Tm³⁺), ¹G₄(Tm³⁺)→¹D₂(Tm³⁺)} and {¹G₄(Tm³⁺)→³F₄(Tm³⁺), ³H₄(Tm³⁺)→¹D₂(Tm³⁺)} between Tm³⁺ ions. In addition, the upconversion luminescence of ¹G₄ and ³H₄ state results respectively from the sequential energy transfer {²F_5/2(Yb³⁺)→²F_7/2(Yb³⁺), ³H₄(Tm³⁺)→¹G₄(Tm³⁺)} and {²F_5/2(Yb³⁺) →²F_7/2(Yb³⁺), ³F₄(Tm³⁺)→³F₂(Tm³⁺)} from Yb³⁺ ions to Tm³⁺ ions. Supported by the National Natural Science Foundation of China (Grant No. 10674019)     

Rashba spin-orbit coupling probed by the weak antilocalization analysis in InAlAs/InGaAs/InAlAs quantum wells as a function of quantum well asymmetry

We have investigated the values of the Rashba spin-orbit coupling constant alpha in In(0.52)Al(0.48)As/In(0.53)Ga(0.47)As/In(0.52)Al(0.48)As quantum wells using the weak antilocalization (WAL) analysis as a function of the structural inversion asymmetry (SIA) of the quantum wells. We have found that the deduced alpha values have a strong correlation with the degree of SIA of the quantum wells as predicted theoretically. The good agreement between the theoretical and experimental values of alpha suggests that our WAL approach for deducing alpha values provides a useful tool in designing future spintronics devices that utilize the Rashba spin-orbit coupling.     

Spin-filter device based on the Rashba effect using a nonmagnetic resonant tunneling diode

We propose an electronic spin-filter device that uses a nonmagnetic triple barrier resonant tunneling diode (TB-RTD). This device combines the spin-split resonant tunneling levels induced by the Rashba spin-orbit interaction and the spin blockade phenomena between two regions separated by the middle barrier in the TB-RTD. Detailed calculations using the InAlAs/InGaAs material system reveal that a splitting of a peak should be observed in the I-V curve of this device as a result of the spin-filtering effect. The filtering efficiency exceeds 99.9% at the peak positions in the I-V curve.