First asymmetric enantioselective total synthesis of phenanthridine alkaloid, (S)-(+)-asiaticumine and its enantiomer

In this study, the first asymmetric enantioselective total syntheses of (+)-asiaticumine A (2) and its enantiomer were accomplished through a seven-step sequence using the bond formation between the C4a and N5 positions of the phenanthridine framework based on the microwave-assisted electrocyclization of cyclohexenylbenzaldoxime methyl ether as an aza 6π-hexatriene system followed by the Sharpless asymmetric dihydroxylation as the key step. In addition, the absolute configuration of natural (+)-2 was determined to be S by Mosher’s method.     

Palladium-catalyzed Mizoroki-Heck reactions in water using thermoresponsive polymer micelles

Palladium-catalyzed Mizoroki-Heck reactions were carried out in water using thermoresponsive polymer micelles. The micelles were generated from thermoresponsive block copolymers consisting of a poly(N-isopropylacrylamide) (PNIPAAm) segment and a hydrophilic segment such as nonionic poly(ethylene glycol) (PEG) (2) and anionic poly(sodium p-styrenesulfonate) (PSSNa) (9). These copolymers exhibited lower critical solution temperature (LCST) behavior at ca. 40–50?°C and showed thermal stimuli-induced formation and dissociation of micelles. The copolymers formed micelles in aqueous solution at higher temperature, where catalytic reactions proceeded. At lower temperature, the micelles dissociated to form a clear solution, enabling efficient extraction of the products from aqueous reaction mixture. In the presence of these copolymers, palladium complexes catalyzed the coupling reactions between aryl iodides and alkene compounds inside the hydrophobic micelle cores in water under relatively milder conditions. Extraction of the products from the aqueous solution of 2 or 9 was found to be efficient enough in comparison with conventional surfactants.     

Energy‐resolved mass spectrometry for differentiation of the fluorine substitution position on the phenyl ring of fluoromethcathinones

A reliable method for structural analysis is crucial for the forensic investigation of new psychoactive substances (NPSs). Towards this end, mass spectrometry is one of the most efficient and facile methods for the identification of NPSs. However, the differentiation among 2‐, 3‐, and 4‐fluoromethcathinones (o‐, m‐, and p‐FMCs), which are ring‐fluorinated positional isomers part of the major class of NPSs referred to as synthetic cathinones, remains a challenge. This is mostly due to their similar retention properties and nearly identical full scan mass spectra, which hinder their identification. In this study, we describe a novel and practical method for differentiating the fluorine substitution position on the phenyl ring of FMCs, based on energy‐resolved mass spectrometry (ERMS) using an electron ionization‐triple quadrupole mass spectrometer. ERMS measurements showed that the three FMC positional isomers exhibited differences in relative abundances of both the fluorophenyl cation (m/z 95) and the fluorobenzoyl cation (m/z 123). The logarithmic plots of the abundance ratio of these two cations (m/z 95 to m/z 123) as a function of the collision energy (CE) followed the order of o‐FMC < p‐FMC < m‐FMC at each CE, which allowed the three isomers to be unambiguously and reliably differentiated. The theoretical dissociation energy calculations confirmed the relationship obtained by ERMS analyses, and additional ERMS measurements of methylmethcathinone positional isomers showed that the differences in abundance among the FMCs were attributed to the differences in their collision‐induced dissociation reactivities arising from the halogen‐induced resonance effects on the phenyl ring. Moreover, the method for differentiation described herein was successfully applied to the actual samples containing seized drugs. We expect that the described methodology will also contribute significantly to the reliable and accurate structural identification of NPSs in the fields of therapeutic, clinical, and forensic toxicology.     

Structure elucidation of cyasterone stereoisomers isolated from Cyathula officinalis

Chemical investigation of ecdysteroidal constituents of the roots and stems of Cyathula officinalis led to the isolation of two cyasterone stereoisomers, 2 and 3, together with the known cyasterone 1. The structures of compounds 2 and 3 were determined to be 28-epi-cyasterone and 25-epi-28-epi-cyasterone, respectively, by means of spectroscopic analysis. X-Ray structures of 1 and 2 confirmed the 24S,25S,28R configuration for 1 and 24S,25S,28S for 2.     

Benzimidazole-5-sulfonamides as novel nonpeptide luteinizing hormone releasing hormone (LHRH) antagonists: minimization of mechanism-based CYP3A4 inhibition

Herein we report the development of novel, potent and non-peptide luteinizing hormone releasing hormone (LHRH) antagonists. The optimization towards derivatives free from mechanism-based CYP3A4 inhibition is described. The identification of a main metabolite guided us towards structural modifications of the benzyl moiety, which resulted in significant improvements of the CYP3A4 profile, while maintaining potent LHRH antagonist activity.     

Supercurrent through hybrid junctions with anisotropic Cooper-pair condensates

A general formula for the supercurrent between different internal structures in a wide class of hybrid junctions is derived on the basis of the Andreev-reflection picture. The formula extends existing formulas and also enables us to analyze novel B-phase/A-phase/B-phase junctions in superfluid 3He systems. We propose a mechanism for pi states due to the (circumflex)l texture in the A phase of the junction, which could elucidate major features of the pi states with higher critical current ( H states) discovered in superfluid 3He weak links. The bistability of the pi states is also discussed.     

Enhanced Coupling of Light from Organic Electroluminescent Device Using Diffusive Particle Dispersed High Refractive Index Resin Substrate

To improve light extraction from organic electroluminescent (EL) devices, we introduced a diffusive substrate with 25 μm thickness consisting of high refractive index resin and scattering particles. It is expected that the diffusive substrate with high refractive index matrix converts the waveguided emission into external emission from both glass substrate and indium-tin-oxide/organic layer. We used the ray tracing method to optimize the scattering effect and to verify the coupling out effect of the diffusive high refractive index substrate. With the use of the ray tracing calculation, an increase in the external emission up to a factor of 2.7 was expected compared to use of a common glass substrate. Experimentally, the coupling out effect of the diffusive high refractive index substrate strongly depended on the thickness of electron transporting layer (ETL) due to the well-known interference effect. The current efficiency increased by a factor of 1.3 for an organic EL device with a 60-nm-thick ETL and by a factor of 6.8 for one with a 120-nm-thick ETL.     

A note on extensions of algebraic and formal groups I

Partially supported by Grant-in-Aid for Scientific Research #62540066