Metal array fabrication through self-assembly of Pt-complex-bound amino acids

A new type of Pt-complex-bound amino acid was synthesized by condensation of a cyclometalated Pt complex with the side-chain residue of N- and C-alkylated glutamic acid. Self-assembly of the Pt-bound lipophilic amino acid afforded a supramolecular gel in organic solvents, which comprised fibrous lamellar aggregates that supported a highly oriented Pt array.     

A triphenylamine double-decker: from a delocalized radical cation to a diradical dication with an excited triplet state

The redox properties and electronic structures of polycationic species were examined using a triphenylamine double-decker species. The double-decker has a strong electron-donating ability, and the spin in the radical cation is delocalized over the whole caged skeleton, despite no direct transannular π-π interaction between two TPA decks. Moreover, the diradical dication has spin-singlet character, despite the meta-phenylene linkage.     

Baeyer-villiger oxidation and oxidative cascade reactions with aqueous hydrogen peroxide catalyzed by lipophilic li[b(c(6) f(5) )(4) ] and ca[b(c(6) f(5) )(4) ](2)

Efficient and selective: Two lipophilic catalysts were used for Baeyer-Villiger (BV) oxidations to give lactones in high yields. Cascade reactions involving this BV oxidation were used to selectively obtain either unsaturated carboxylic acids or hydroxylactones in high yields from β-silyl cyclohexanones.     

The first total synthesis and reassignment of the relative stereochemistry of 16-hydroxy-16,22-dihydroapparicine

We report the first total synthesis and reassignment of the relative stereochemistry of naturally occurring 16-hydroxy-16,22-dihydroapparicine. Our novel route proceeds by a cascade reaction to efficiently construct a 1-azabicyclo[4.2.2]decane core, along with two stereocenters (C-15 and C-16). The C-16 quaternary carbon was constructed through stereospecific 1,2-addition using an indole nucleophile to an aldehyde or a methylketone. The stereospecific synthesis of two diastereomers of the target product has revealed the true relative stereochemistry of the natural compound.     

Development of an efficient liquid-phase peptide synthesis protocol using a novel fluorene-derived anchor support compound with Fmoc chemistry; AJIPHASE®

The development of a novel fluorene-type anchor support molecule and a liquid-phase peptide synthesis protocol (AJIPHASE®) is reported. With this support molecule, the synthesis of a protected peptide with a free carboxyl group could be carried out by repeated coupling/deprotection reactions and isolation by simple precipitation. Cleavage is performed under mild acidic conditions (2% TFA/CHCl₃ or hexafluoroisopropanol) to release the products in good yield and purity. There were no signs of either diketopiperazine formation or the removal of protective groups in the side-chain.     

Synthesis of unsymmetrically disubstituted ethynes by the palladium/copper(I)-cocatalyzed sila-Sonogashira–Hagihara coupling reactions of alkynylsilanes with aryl iodides,bromides, and chlorides through a direct activation of a carbon–silicon bond

In this paper, we explore the copper/palladium-cocatalyzed cross-coupling reactions of 1-aryl-2-trimethylsilylethynes with aryl iodides, bromides, and chlorides as coupling partners, to furnish unsymmetrically disubstituted ethynes in moderate to excellent yields. Various aryl iodides were subjected to reaction under the optimized conditions with 5 mol % of Pd(PPh₃)₂ and 50 mol % of CuCl. The steric properties of the aryl iodide proved more influential to the outcome of the cross-coupling reaction than electronic factors. In addition, we succeeded in synthesizing unsymmetrical diarylethynes using two different aryl iodides in one-pot. Furthermore, under the same reaction conditions with 10 mol % of PdCl₂, 40 mol % of P(4-FC₆H₄)₃, and 50 mol % of CuCl as catalyst, we succeeded in synthesizing unsymmetrical diarylethynes from various aryl bromides. Finally, we explored reactions with aryl chlorides and duly discovered that unsymmetrical diarylethynes were obtainable in moderate to good yields when 10 mol % of Pd(OAc)₂, 10 mol % of (?)-DIOP, and 10 mol % of CuCl were used. These reactions proceed through a direct activation of a carbon–silicon bond in alkynylsilanes by CuCl to generate the corresponding alkynylcopper species via transmetalation from silicon to copper. Mechanistic investigations on the reaction of alkynylsilanes with aryl bromides confirmed that the trimethylsilyl bromide generated in situ retarded both transmetalation steps between CuCl and alkynylsilane, and between palladium(II) species formed by oxidative addition and alkynylcopper species.     

Spray freeze-dried porous microparticles of a poorly water-soluble drug for respiratory delivery

Particles of poorly water-soluble drugs were prepared to develop a dry powder inhaler (DPI). Spray freeze-drying (SFD) technique using a four-fluid nozzle (4N), which has been developed by authors, was applied in this research. Ciclosporin and mannitol were used as a poorly water-soluble model drug and a dissolution-enhanced carrier, respectively. The organic solution of ciclosporin and aqueous solution of mannitol were separately and simultaneously atomized through the 4N, and the two solutions were collided with each other at the tip of the nozzle edge. The spray mists were immediately frozen in liquid nitrogen to form a suspension. Then, the iced droplets were freeze-dried to prepare the composite particles of the drug and carrier. tert-Butyl alcohol (t-BuOH) was used as the organic spray solvent due to its relatively high freezing point. The resultant composite particles with varying drug content were characterized depending on their morphological and physicochemical properties. The particles contained amorphous ciclosporin and δ-crystalline mannitol. The characteristic porous structure of SFD particles potentially contributed to their good aerodynamic performance. A series of particles with a similar size distribution and different drug content revealed that the incorporation of mannitol successfully improved the cohesive behavior of ciclosporin, leading to enhanced aerosol dispersion. The dissolution test method using low-volume medium was newly established to simulate the release process from particles deposited on the surface of the bronchus and pulmonary mucosa. The composite with hydrophilic mannitol dramatically improved the in vitro dissolution behavior of ciclosporin in combination with the porous structure of SFD particles.     

Molecular dynamics simulation of quasi-two-dimensional water clusters on ice nucleation protein

We performed molecular dynamics simulations of systems that consisted of the ice nucleation protein and the quasi-two-dimensional water cluster on it. The angle distributions, percolation probabilities, mean cluster sizes, cluster size distributions, and hydrogen bond relaxation times were analyzed. We concluded that the behavior of the water clusters on the ice nucleation protein was elaborately intertwined by the interaction between the ice nucleation protein and water, the interaction between the water molecules and the effect of temperature. The percolation probability and mean cluster size depended on the interactions and temperatures.     

Stereocontrolled synthesis of substituted chiral piperidines via one-pot asymmetric 6π-azaelectrocyclization: asymmetric syntheses of (-)-dendroprimine, (+)-7-epidendroprimine, (+)-5-epidendroprimine, and (+)-5,7-epidendroprimine

The asymmetric one-pot 6π-azaelectrocyclization of alkenyl vinyl stannane, ethyl (Z)-2-iodo-4-oxobutenoate, and (-)-7-isopropyl-cis-aminoindanol in the presence of a Pd(0) catalyst stereoselectively produced the tetracyclic aminoacetal compounds, resulting from the four-bond formation accompanying by controlling the stereochemistry at the two asymmetric centers. The produced cyclic aminoacetals can be regarded as synthetic precursors of substituted chiral piperidines, and the syntheses of 2,4- and 2,4,6-substituted piperidines were realized from the obtained aminoacetals by the stereoselective hydrogenation of the double bond conjugated with the C-4 ester group and alkylation at the aminoacetal moiety. In addition, the stereoselective synthesis of an indolizidine alkaloid, (-)-dendroprimine, and its three stereoisomers, (+)-7-epidendroprimine, (+)-5-epidendroprimine, and (+)-5,7-epidendroprimine, were achieved.