A fluorimetric, column-switching HPLC and its application to an elimination study of LLU-alpha enantiomers in rat plasma

A method for the enantiomeric determination of 2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxy chroman (LLU-alpha, gamma-CEHC) in rat plasma was developed using high-performance liquid chromatography (HPLC) with a fluorimetric derivatization with 4-N, N-dimethylaminosulfonyl-7-piperazino-2,1,3-benzoxadiazole (DBD-PZ) followed by O-acetylation with acetyl chloride. The proposed HPLC system used two non-chiral columns (phenyl and octadecylsilica) and a chiral column (a modified cellulose type), which were connected via two column-switching valves. A derivatized sample prepared from rat plasma was first separated on the phenyl column, and the fraction including LLU-alpha derivative was introduced to the octadecylsilica column to quantify the concentration of the mixture of S- and R-LLU-alpha. Finally, the LLU-alpha derivative was directly injected into the chiral column to obtain the ratio of the enantiomers. The proposed HPLC system was applied to the enantiomeric determination of LLU-alpha in plasma after intravenous administration of racemic LLU-alpha. S-LLU-alpha was eliminated faster than R-LLU-alpha, and its concentration in plasma decreased to one-third at 2 min after dosing.     

Continuous Synthesis of Aryl Amines from Phenols Utilizing Integrated Packed-Bed Flow Systems

Aryl amines are important pharmaceutical intermediates among other numerous applications. Herein, an environmentally benign route and novel approach to aryl amine synthesis using dehydrative amination of phenols with amines and styrene under continuous-flow conditions was developed. Inexpensive and readily available phenols were efficiently converted into the corresponding aryl amines, with small amounts of easily removable co-products (i.e., H₂O and alkanes), in multistep continuous-flow reactors in the presence of heterogeneous Pd catalysts. The high product selectivity and functional-group tolerance of this method allowed aryl amines with diverse functional groups to be selectively obtained in high yields over a continuous operation time of one week.     

Separability criterion for quantum effects

Entanglement of quantum states is absolutely essential for modern quantum sciences and technologies. It is natural to extend the notion of entanglement to quantum observables dual to quantum states. For quantum states, various separability criteria have been proposed to determine whether a given state is entangled. In this Letter, we propose a separability criterion for specific quantum effects (binary observables) that can be regarded as a dual version of the Bell–Clauser–Horne–Shimony–Holt (Bell–CHSH) inequality for quantum states. The violation of the dual version of the Bell–CHSH inequality is confirmed by using IBM's cloud quantum computer. As a consequence, the violation of our inequality rules out the maximal tensor product state space, that satisfies information causality and local tomography. As an application, we show that an entangled observable which violates our inequality is useful for quantum teleportation.     

Einstein equations and Lagrangians on symmetry-restricted phase spaces

When Lagrangians are restricted to subspaces of the phase space satisfying certain symmetry conditions, they do not always yield the correct Einstein equations. An example was found by Hawking in the Lagrangian for spatially homogeneous universes. First we show that this problem is not limited to general relativity. Then we visualize certain terms which do not appear in Lagrangians on symmetry-restricted phase spaces but which nevertheless contribute to the Euler-Lagrange derivatives. We apply our general formula to the Schwarzschild metric, the Friedmann universes, and spatially homogeneous universes.     

Continuous Synthesis of Aryl Amines from Phenols Utilizing Integrated Packed‐Bed Flow Systems

Aryl amines are important pharmaceutical intermediates among other numerous applications. Herein, an environmentally benign route and novel approach to aryl amine synthesis using dehydrative amination of phenols with amines and styrene under continuous‐flow conditions was developed. Inexpensive and readily available phenols were efficiently converted into the corresponding aryl amines, with small amounts of easily removable co‐products (i.e., H₂O and alkanes), in multistep continuous‐flow reactors in the presence of heterogeneous Pd catalysts. The high product selectivity and functional‐group tolerance of this method allowed aryl amines with diverse functional groups to be selectively obtained in high yields over a continuous operation time of one week.     

Nickel-Catalyzed Reductive Allyl−Aryl Cross-Electrophile Coupling via Allylic C−F Bond Activation

Nickel-catalyzed reductive cross-coupling of allylic difluorides with aryl iodides was achieved via allylic C−F bond activation. Based on this protocol, a series of γ-arylated monofluoroalkenes were synthesized in moderate to high yields with high Z-selectivities. Mechanistic studies suggest that the C−I bonds of the aryl iodides and the C−F bonds of the allylic difluorides were cleaved via oxidative addition and β-fluorine elimination, respectively, where the oxidative addition of less reactive C−F bonds was avoided to permit their transformation.