Ruthenium complex-catalyzed allylic alkylation of carbonucleophiles with allylic carbonates

Allylic carbonates except for allyl methyl carbonate reacted with carbonucleophiles such as ethyl acetoacetate in the presence of a catalytic amount of Ru(cod)(cot) [cod = cycloocta-1,5-diene, COT = cycloocta-1,3,5-triene] in N-methylpiperidine at 80°C to give the corresponding monoallylated carbonucleophiles in high yields with high regioselectivity. The regioselectivity was quite different from that in the palladium-catalyzed reactions. The allylation of carbonucleophiles using allyl methyl carbonate selectively gave the diallylated carbonucleophiles in high yields.     

Benchmark results in vector atmospheric radiative transfer

In this paper seven vector radiative transfer codes are inter-compared for the case of underlying black surface. They include three techniques based on the discrete ordinate method (DOM), two Monte-Carlo methods, the successive orders scattering method, and a modified doubling-adding technique. It was found that all codes give very similar results. Therefore, we were able to produce benchmark results for the Stokes parameters both for reflected and transmitted light in the cases of molecular, aerosol and cloudy multiply scattering media. It was assumed that the single scattering albedo is equal to one. Benchmark results have been provided by several studies before, including Coulson et al. [22], Garcia and Siewert [7], [8], Wauben and Hovenier [10], and Natraj et al. [11] among others. However, the case of the elongated phase functions such as for a cloud and with a high angular resolution is presented here for the first time. Also in difference with other studies, we make inter-comparisons using several codes for the same input dataset, which enables us to quantify the corresponding errors more accurately.     

Effect of static pressure on acoustic energy radiated by cavitation bubbles in viscous liquids under ultrasound

The effect of static pressure on acoustic emissions including shock-wave emissions from cavitation bubbles in viscous liquids under ultrasound has been studied by numerical simulations in order to investigate the effect of static pressure on dispersion of nano-particles in liquids by ultrasound. The results of the numerical simulations for bubbles of 5 μm in equilibrium radius at 20 kHz have indicated that the optimal static pressure which maximizes the energy of acoustic waves radiated by a bubble per acoustic cycle increases as the acoustic pressure amplitude increases or the viscosity of the solution decreases. It qualitatively agrees with the experimental results by Sauter et al. [Ultrason. Sonochem. 15, 517 (2008)]. In liquids with relatively high viscosity (～200 mPa s), a bubble collapses more violently than in pure water when the acoustic pressure amplitude is relatively large (～20 bar). In a mixture of bubbles of different equilibrium radius (3 and 5 μm), the acoustic energy radiated by a 5 μm bubble is much larger than that by a 3 μm bubble due to the interaction with bubbles of different equilibrium radius. The acoustic energy radiated by a 5 μm bubble is substantially increased by the interaction with 3 μm bubbles.     

Forcings with the countable chain condition and the covering number of the Marczewski ideal

We prove that the covering number of the Marczewski ideal is equal to ₁ in the extension with the iteration of Hechler forcing.     

Ruthenium-catalyzed formal [4 + 2] cycloaddition of alkynes with alkenes: formation of cyclohexenedicarboxylates via isomerization of alkynes and successive Diels-Alder reaction

Formal [4 + 2] cycloaddition of alkynes with electron-deficient alkenes, which affords 3,6-dialkyl-4-cyclohexene-1,2-dicarboxylates, was achieved using Ru(η⁶-1,3,5-cyclooctatriene)(η²-dimethyl fumarate)₂ as a catalyst. The reaction mechanism consists of two steps, isomerization of an alkyne to conjugated dienes and successive Diels-Alder reaction of the generated dienes with an electron-deficient alkene.     

Dioxygenation of human serum albumin having a prosthetic heme group in a tailor-made heme pocket

Human serum albumin (HSA) is the most abundant plasma protein in our bloodstream and serves as a transporter for small hydrophobic molecules such as fatty acids, bilirubin, and steroids. Hemin dissociated from methemoglobin is also bound within a narrow D-shaped cavity in subdomain IB of HSA. In terms of the general hydrophobicity of the alpha-helical pocket, HSA potentially has features similar to the heme-binding site of myoglobin (Mb) or hemoglobin (Hb). However, the reduced ferrous HSA-heme complex is immediately oxidized by O2, because HSA lacks the proximal histidine that enables the heme group to bind O2. In this paper, we report the introduction of a proximal histidine into the subdomain IB of HSA by site-directed mutagenesis to construct a tailor-made heme pocket (I142H/Y161L), which allows a reversible O2 binding to the prosthetic heme group. Laser flash photolysis experiments revealed that this artificial hemoprotein appears to have two different geometries of the axial-imidazole coordination, and these two species (I and II) showed rather low O2 binding affinities (P1/2O2 = 18 and 134 Torr) relative to those of Mb and Hb.     

Convenient synthesis of 2-alkylamino-6-carboxy-5,7-diarylcyclopenteno[1,2-b]pyridines via direct acylamination with imidoyl chlorides

A robust synthetic method for 2-alkylamino-6-carboxy-5,7-diarylcyclopenteno[1,2-b]pyridines via acylamination at the alpha position of the functionalized pyridine system has been developed. The key step in this method was achieved by treatment of the corresponding pyridine N-oxides with 2.5 equiv of imidoyl chlorides in the presence of triethylamine, thus producing the desired 2-acylaminopyridines in good yields (74-96%).     

Effect of structural relaxation on the physical and aerosol properties of amorphous form of FK888 (NK1 antagonist)

FK888 (NK1 antagonist) is a candidate drug for migraine and selected as a model of amorphous drug. FK888 was micronized to develop as dry powder inhalers (DPIs) taking into consideration of its water insoluble property. The glass transition temperature (Tg) and fragility (m) were 90 degrees C and 118, respectively, and it was categorized as a fragile glass based on Angell's concept. FK888 was structurally relaxed by aging below Tg, then the effect of aging on their physical and aerosol properties were investigated. The investigation on the moisture sorption-desorption isotherms of FK888 indicated that aged FK888 adsorbed less amount of water than that of unaged FK888. This unique moisture sorption-desorption behavior of the aged sample is explained by structural relaxation accompanying decrease of free volume and/or increase of density. As for the dissolution rate of unaged and aged FK888, they showed the similar value, suggesting that there would be no difference in bioavailability. In relation to the stability, FK888 DPIs prepared by unaged and aged FK888 were stored at 70 degrees C, and the respirable fraction of FK888 DPIs was evaluated by using multistage cascade impactor (USP apparatus 3). As a result, the respirable fraction of FK888 DPIs prepared by unaged sample was significantly decreased compared to the aged sample, suggesting that agglomeration may occur in the unaged sample during the storage. This phenomenon was supported by that the unaged sample showed a significant decrease in the surface area compared to that of the aged sample when stored at various conditions.