Prodrugs of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine: potent interferon inducing agents in monkeys

In order to improve the oral bioavailability of 9-benzyl-8-hydroxy-2-(2-hydroxyethylthio)adenine (SM-295072), a potent interferon (IFN) inducing agent, we synthesized prodrugs of it by utilizing the hydroxy groups at the C(2)-side chain and/or the C(8)-position. The carbonate prodrug at the C(8)-position was more effective than that at the C(2)-side chain for oral absorption in rats. Among the compounds prepared, compound 6 demonstrated the most preferable prodrug properties, and the maximum plasma concentration of 6 was approximately 4-fold higher than that of SM-295072. Furthermore, compound 6 was dose-dependently absorbed in monkeys by oral administration, and exhibited a potent IFN-inducting activity that correlated well with its plasma drug concentration.     

Pd-catalyzed asymmetric allylic amination using aspartic acid derived P-chirogenic diaminophosphine oxides: DIAPHOXs

[reaction: see text] A Pd-catalyzed asymmetric allylic amination using aspartic acid derived P-chirogenic diaminophosphine oxides (DIAPHOXs) is described. Asymmetric allylic amination of both linear and cyclic substrates proceeded at room temperature to give the chiral allylic amines in 72-99% ee.     

Ir-catalyzed asymmetric allylic amination using chiral diaminophosphine oxides

An Ir-catalyzed asymmetric allylic amination using chiral diaminophosphine oxide is described. Asymmetric allylic amination of terminal allylic carbonates proceeded in the presence of 2 mol % of Ir catalyst, 2 mol % of chiral diaminophosphine oxide, 5 mol % of NaPF₆, and BSA, affording the chiral branched allylic amines in up to 95% ee.     

Systematic study of photoluminescence upon band gap excitation in perovskite-type titanates R1/2Na1/2TiO3:Pr (R=La, Gd, Lu, and Y)

Pr³⁺-doped perovskites R_1/2Na_1/2TiO₃:Pr (R=La, Gd, Lu, and Y) were synthesized, and their structures, optical absorption and luminescent properties were investigated, and the relationship between structures and optical properties are discussed. Optical band gap of R_1/2Na_1/2TiO₃ increases in the order R=La, Gd, Y, and Lu, which is primarily due to a decrease in band width accompanied by a decrease in Ti-O-Ti bond angle. Intense red emission assigned to f-f transition of Pr³⁺ from the excited ¹D₂ level to the ground ³H₄ state upon the band gap photo-excitation (UV) was observed for all compounds. The wavelength of emission peaks was red-shifted in the order R=La, Gd, Y, and Lu, which originates from the increase in crystal field splitting of Pr³⁺. This is attributed to the decrease in inter-atomic distances of Pr-O together with the inter-atomic distances (R, Na)-O, i.e., increase in covalency between Pr and O. The results indicate that the luminescent properties in R_1/2Na_1/2TiO₃:Pr are governed by the relative energy level between the ground and excited state of 4f² for Pr³⁺, and the conduction and valence band, which is primarily dependent on the structure, e.g., the tilt of TiO₆ octahedra and the Pr-Ti inter-atomic distance and the site symmetry of Pr ion.     

Enantioselective total syntheses of (+)-decursin and related natural compounds using catalytic asymmetric epoxidation of an enone

The enantioselective total syntheses of (+)-decursin (1) and related natural dihydropyranocoumarins (−)-prantschimgin (3), (+)-decursinol (4), and (+)-marmesin (5) were achieved for the first time using catalytic asymmetric epoxidation of an enone as the key step. Catalytic asymmetric epoxidation of the enone was effectively promoted by the novel multifunctional asymmetric catalyst generated from La(O-i-Pr)₃, BINOL, and Ph₃AsO in a 1:1:1 ratio to afford epoxide in 94% yield and 96% ee, which was recrystallized to give optically pure epoxide. After conversion to the common key intermediate (−)-peucedanol (7), all natural dihydropyranocoumarins were synthesized through palladium-catalyzed intramolecular C-O coupling reactions. A possible reaction mechanism of the catalytic asymmetric epoxidation of enones is also described based on X-ray analysis, laser desorption/ionization time-of-flight mass spectrometry, kinetic studies, and asymmetric amplification studies.     

Synthesis of the novel perovskite-type oxyfluoride PbScO2F under high pressure and high temperature

We synthesized a novel perovskite-type oxyfluoride, PbScO₂F, and investigated its crystal structure, thermal stability and dielectric properties. PbScO₂F has a cubic perovskite-type structure with Pb ions displaced from the ideal A-site positions along the 〈110〉 direction. By thermal gravity and differential thermal analyses, we found that this compound is stable up to 963 K (690 °C) under ambient atmosphere. The dielectric permittivity of PbScO₂F is approximately 80, at room temperature, which is almost the same as KTiO₂F and smaller than that of PbFeO₂F. Furthermore, an anomaly in the dielectric permittivity was observed in the vicinity of 100 K that seems to be related to the displacement of the Pb ions.     

High-pressure synthesis, structure, and characterization of a post-perovskite CaPtO3 with CaIrO3-type structure

A new ternary platinum oxide, CaPtO3 was synthesized under a pressure of 7 GPa and a temperature of 1000 degrees C. The crystal structure of CaPtO3 was determined by Rietveld analysis of the X-ray powder diffraction data. CaPtO3 has a layered CaIrO3-type structure (orthorhombic, space group: Cmcm), which is the same as that of a post-perovskite MgSiO3 in the Earth's lower mantle. The magnetic susceptibility data indicate that the Pt ion in CaPtO3 is tetravalent in the low spin state with an electron configuration of t2g(6)eg(0)(S = 0). This finding is consistent with the insulating behavior.     

Enantioselective formal synthesis of (−)-aurantioclavine using Pd-catalyzed cascade cyclization and organocatalytic asymmetric aziridination

The enantioselective formal synthesis of (?)-aurantioclavine is described. The core tricyclic skeleton was synthesized using a Pd-catalyzed Heck insertion–allylic amination cascade. The stereocenter was constructed by a highly enantioselective organocatalytic asymmetric aziridination reaction.     

Synthesis of functionalized iodoalkenes using a multicomponent reaction triggered by electrophilic iodination of alkenyldiazoacetates

Diazo compounds are frequently used as precursors of metal carbenoids and act as soft nucleophiles even without the use of metal catalysts. The resulting diazonium species may also be trapped by various nucleophiles. The introduction of an iodine functionality applicable for the coupling reaction into an alkenyl diazo compound, however, has not been reported. We developed iodoalkoxylation reactions of alkenyl diazoacetates using an electrophilic iodinating reagent and oxygen nucleophile. This catalyst-free multicomponent reaction proceeded regioselectively, furnishing trisubstituted vinyl iodides in 31%–71% yield. The synthesized iodoalkenes were converted into the corresponding olefins with various functionalities in good yield via Suzuki-Miyaura coupling reactions with arylboronic acids under palladium catalysis to demonstrate the synthetic utility of the developed reaction sequence.     

Real-time observation on surface diffusion and molecular orientations for phthalocyanine thin films at nanometer spacial resolution

The morphology, electronic structure and ordering of the phthalocyanine thin films have been investigated at nanometer scale by photoelectron emission microscopy (PEEM) excited by polarized soft X-rays from synchrotron light source. The sample investigated was micropattern of silicon phthalocyanine deposited on gold surface. The incident angle dependences of the X-ray absorption near edge structure (XANES) spectra at the silicon K-edge revealed that the molecules of 5-layered films are lying nearly flat on the surface. Clear image of the micropattern was observed by PEEM, showing that the molecules are deposited via Volmer–Weber (VW) mode at room temperature. While, the surface diffusion was observed upon heating, and the micropattern image almost disappeared at 240 °C, representing the deposition mode changes from VW-mode to Frank–van der Merwe (FM)-one. On the basis of the photon-energy dependences of the brightnesses in the PEEM images, it was found that the molecules diffusing to the fresh gold surface rather stand-up at 240 °C. The observed changes in the molecular orientations at nanometer domains are discussed on the basis of the strengths of the molecule–molecule and molecule–surface interactions.