Asymmetric Friedel-Crafts-Type Reaction of 2-Vinylindoles to N-Boc Imines Using a Chiral Imidazolidine-Containing NCN-Pincer Pd Catalyst.

A chiral imidazolidine-containing NCN-pincer Pd-OTf complex (NCN-Pd cat) promoted the asymmetric nucleophilic addition of unprotected 2-vinylindoles to N-Boc imines in a Friedel-Crafts-type manner. The chiral (2-vinyl-1H-indol-3-yl)methanamine products become nice platforms for constructing multiple ring systems.

Solvent-Dependent Conformational Switching of N-Methyl-N,N'-diarylsquaramide.

N,N'-Diarylsquaramide and N,N'-dialkylsquaramide are conformationally stable linkers with extended (trans, trans) and folded (cis, cis) structures, respectively, independently of external conditions. Here, we show that N-monomethylated N,N'-diarylsquaramides generally take a (trans, cis) structure in the crystal but show a solvent-dependent conformational equilibrium in solution. In particular, the stable conformer of N-methyl-N,N'-bis(1-naphthyl)squaramide (1f) changes depending upon the solvent. Thus, aromatic N-monomethylated squaramides could find application as components of environment-responsive molecular switches.

Molecular Dynamics Studies of the Ho(III) Aqua-tris(dibenzoylmethane) Complex: Role of Water Dynamics.

The seven-coordinate Ho(III) aqua-tris(dibenzoylmethane)(DBM) complex, referred to as Ho-(DBM)3·H2O, was first reported in the late 1960s. It has a threefold symmetric structure, with Ho at the center of three dibenzoylmethane ligands and hydrogen-bonded water to ligands. It is considered that the hydrogen bonds between the water molecule and the ligands surrounding Ho play an important role in the formation of its symmetrical structure. In this work, we developed new force-field parameters for classical molecular dynamics (CMD) simulations to theoretically elucidate the structure and dynamics of Ho-(DBM)3·H2O. To develop the force field, structural optimization and molecular dynamics were performed on the basis of ab initio calculations using the plane-wave pseudopotential method. The force-field parameters for CMD were then optimized to reproduce the data obtained from ab initio calculations. Validation of the developed force field showed good agreement with the experimental crystalline structure and ab initio data. The vibrational properties of water in Ho-(DBM)3·H2O were investigated by comparison with bulk liquid water. The vibrational motion of water was found to have a characteristic mode originating from stationary rotational motion along the c-axis of Ho(III) aqua-tris(dibenzoylmethane). Contrary to expectations, the hydrogen-bond dynamics of water in Ho-(DBM)3·H2O were found to be almost equivalent to those of bulk liquid water except for librational motion. This development route for force-field parameters for CMD and the establishment of water dynamics can advance the understanding of water-coordinated metal complexes with high coordination numbers such as Ho-(DBM)3·H2O.

Borocyclic Radicals Prepared from Orthoquinone-Containing Polycyclic Aromatics by Photoirradiation.

Borocyclic radicals with highly conjugated aromatics were generated from orthoquinone-containing polycyclic aromatic compounds by trapping the photoinduced triplet state with simple boron halide under irradiation with light of appropriate wavelength. The picene-based borocyclic radical was remarkably stable when stored at 23 °C in a desiccator for over 1 year. The crystal structure of this stable radical had a stacking structure of a planar π-conjugated system, and the electrical conductivity was higher than those of ordinary organic radical systems.

Conformational Properties of Aromatic Amides Bearing Imidazole Ring and Acid-Induced Trans-Cis Amide Switching.

Aromatic amides bearing secondary amide bond exist in trans conformation both in the crystal and in solution, whereas the conformation of the N-methylated derivatives is cis in the crystal and predominantly cis in various solvents. The cis conformational preference of N-alkylated benzanilide provides access to aromatic foldamers such as oligo(N-alkyl-p-benzamide)s, which adopt dynamic helical structures. Here, the conformational properties of imidazole-substituted amide in the crystal and in solution were examined. Imidazole-substituted amides 2a and 4a existed mainly in the cis conformation in solution. The ratio of the cis conformer of N-methyl-N-(1-methyl-1H-imidazol-4-yl)benzamide (4a) was smaller than that of N,1-dimethyl-N-phenyl-1H-imidazole-2-carboxamide (2a) or N-methylbenzanilide, but the introduction of a substituent strongly affected the conformer ratio. Compounds 6a and 7a bearing an electron-withdrawing group on the imidazole ring existed predominantly in trans form. On the other hand, the introduction of an electron-withdrawing group on the phenyl ring or a bulky substituent on the amide nitrogen of 4a increased the ratio of cis conformer. Further, the major conformer of N-alkylated N-imidazolylamides was switched from cis to trans by the addition of acid. These results suggest that imidazole-substituted amides might be applicable as conformational switches in aromatic foldamers to enable environment-dependent structural change.

Development of Helical Aromatic Amide Foldamers with a Diphenylacetylene Backbone.

We designed and synthesized aromatic polyamides with a diphenylacetylene backbone, α-DPA and ß-DPA, bearing (S)-α- and (S)-ß-methyl-substituted triethyleneglycol (TEG) side chains, respectively, and examined their conformations in solution. Both polymers exhibit strong, solvent polarity-dependent circular dichroism spectra, which indicated that they take helical conformations in low-polarity solvents. The spectra were mirror images, depending on the chiral position of the side chains. Thus, the polyamide α-DPA bearing (S)-α-methyl-substituted TEG groups takes a left-handed helical conformation, while the polyamide ß-DPA with (S)-ß-methyl-substituted TEG groups takes a right-handed helical conformation. The difference in the screw sense of α-DPA and ß-DPA would be caused by the steric interaction between the main chain and the side chain, as observed in poly(p-benzamide) possessing (S)-ß-methyl-substituted TEG side chains (ß-PA) because the large cavity of the helical structure of DPA would disturb the solvophobically induced helical folding. Detailed conformational analyses of the oligoamides 6-12 with ß-methyl-substituted TEG groups were conducted. Theoretical calculations indicated that the oligoamides with ß-methyl-substituted TEG groups exist in a helical conformation with a cavity of 7 Å in diameter. The 1H NMR spectra of the oligomers revealed interactions with small anions such as chloride and acetate anions and with pyridinium cations.

Synthesis and chiroptical properties of cylindrical macrocycles comprising two calix[3]aramide moieties.

Calix[3]aramide-based cylindrical macrocycles were synthesized by the one-step amide coupling reaction of a monomer containing two meta-alkylaminobenzoic acid units linked by para-phenylene bridges. The major products included a meso-form and an enantiomeric pair, with stereochemistry derived from the direction of the amide bonds and their fixed conformation. Mirror-image ECD, VCD, and CPL spectra were observed in the enantiomeric pair and the absolute structure was determined by comparing measured and calculated ECD and VCD spectra.

Catalytic Asymmetric Synthesis of Chiral Bis(indolyl)methanes Using a Ts-PyBidine-Nickel Complex.

A chiral tosyl-substituted bis(imidazolidine)pyridine Ts-PyBidine-nickel complex was an efficient catalyst for Friedel-Crafts reaction of indoles with methylene indolinones to give bisindolylmethane compounds having differently oxidized indole units with high enantioselectivities. Alkylation of the products proceeded smoothly in a highly diastereoselective manner, providing an all-carbon quaternary carbon center without significant loss of enantiomeric excess.

Modifications in coordination structure of Mg[TFSA]2-based supporting salts for high-voltage magnesium rechargeable batteries.

To achieve a sustainable-energy society in the future, next-generation highly efficient energy storage technologies, particularly those based on multivalent metal negative electrodes, are urgently required to be developed. Magnesium rechargeable batteries (MRBs) are promising options owing to the many advantageous chemical and electrochemical properties of magnesium. However, the substantially low working voltage of sulfur-based positive electrodes may hinder MRBs in becoming alternatives to current Li-ion batteries. We proposed halide-free noncorrosive ionic liquid-based electrolytes incorporating Mg[TFSA]2 for high-voltage MRB applications. Upon the complexation of Mg[TFSA]2 with tetraglyme (G4) and strict control of the liquid states, the electrolytes achieved excellent anodic stability up to 4.1 V vs. Mg2+/Mg even at 100 °C. The modest electrochemical activities for magnesium deposition/dissolution in the [Mg(G4)][TFSA]2/ionic liquid electrolyte can be improved by certain modifications to the coordination state of [TFSA]-. Dialkyl sulfone was found to be effective in changing the coordination state of [TFSA]- from associated to isolated (free). This coordination change successfully promoted magnesium deposition/dissolution reactions, particularly in the coexistence of ether ligand. By contrast, the coordination of Mg2+ by strongly donating agents such as dimethyl sulfoxide and alkylimidazole led to the complexes inactive electrochemically, suggesting that interaction between Mg2+ and coordination agents predominates the fundamental electrochemical activity. We also demonstrated that an enhancement in the electrochemical activity of electrolytes contributed to improvements in the cycling ability of magnesium batteries with 2.5 V-class MgMn2O4 positive electrodes.

Morphological and Physicochemical Evaluation of Two Distinct Glibenclamide/Hypromellose Amorphous Nanoparticles Prepared by the Antisolvent Method.

The morphology and stability of amorphous nanoparticles of glibenclamide (GLB) prepared by the antisolvent method using different methods of adding hypromellose (HPMC) were evaluated. Nano-A was prepared by the injection of a dimethyl sulfoxide (DMSO) solution of GLB into the HPMC solution, whereas nano-B was obtained by the injection of a DMSO solution of GLB and HPMC into water. Cryogenic transmission electron microscopy, field-emission scanning electron microscopy, and field-emission transmission electron microscopy, including energy dispersive X-ray spectrometry, revealed that the particles of the nano-A and nano-B samples are hollow spheres and nonspherical nanoparticles, respectively. Powder X-ray diffraction and solid-state NMR measurements showed that GLB is present in an amorphous state in both nano-A and nano-B. The weight ratios of HPMC in the GLB/HPMC nanoparticles were 11 and 16% for nano-A and nano-B, respectively, as determined by solution-state NMR. The glass transition temperatures ( Tg) of nano-A and nano-B evaluated using differential scanning calorimetry were lower by about 10 °C compared to that of amorphous GLB, presumably because of a Tg confinement effect and the surface coverage and mixing of HPMC, as suggested by the inverse gas chromatography experiment. GLB crystallization during storage was suppressed more strongly in nano-B than nano-A, owing to the higher amount of HPMC and the higher miscibility between GLB and HPMC. It is suggested that the diffusion rate of the solvent during nanoprecipitation determined the nanoparticle properties. In nano-A, the precipitation of GLB first occurred at the outer interface because of the rapid diffusion of the solvent. Thus, hollow spherical particles with HPMC preferentially located near the surface were formed. On the other hand, the diffusion of the solvent in nano-B was suppressed because of the presence of HPMC, yielding small nonspherical nanoparticles with a high miscibility of GLB and HPMC.

Synthesis and Conformational Analysis of Alternately N-Alkylated Aromatic Amide Oligomers.

Alternately N-alkylated aromatic amides such as 1-3 bearing various side chains were designed and synthesized as novel helical foldamers. The CD spectra of oligomers with chiral side chains showed a positive Cotton effect, which indicates that these oligomers take helical conformations in solution. The CD intensity gradually increased with increasing chain length, and pentamer 3d showed remarkably strong CD signals in chloroform. The absorption maxima of the UV spectra were increasingly red shifted with increasing chain length, in contrast to the case of poly( p- N-alkylbenzamide)s. Structure optimization of the oligomers based on the crystal structure of 1a as the monomer unit supported the formation of helical structure with a large cavity and also suggested intramolecular hydrogen bond formation between secondary amides. The results of calculation were consistent with the observed spectroscopic features.

Conformational Properties of Aromatic Oligoamides Bearing Pyrrole Rings.

N-Alkylbenzanilides generally exist in cis conformation both in the crystalline state and in various solvents, and this cis conformational preference can be utilized to construct dynamic helical oligoamides. Here, we synthesized the pyrrole-containing amides 2-5 and their oligomers 6-8 and examined their conformations in the crystalline state and in solution. All the N-methylated amides showed cis conformational preference in solution, but the ratio of the cis isomer was decreased when the amide bond was attached at the 4-position of the pyrrole ring, probably because the destabilization of the trans conformer due to electronic repulsion between the pyrrole π electrons and the amide carbonyl lone-pair electrons is reduced due to the small torsion angle between the 5-membered N-pyrrole and the amide bond. In the crystalline state, N-methylated amides showed cis structure, except for compound 5, and cis conformational preference was observed for the pyrrole amides. The CD spectra of oligoamides 15-18 bearing chiral N-substituents were consistent with the presence of dynamic and well-defined chiral foldamers, which were structurally distinct from N-alkylated poly( p-benzamide)s 1.

Chemosynthetic homologues of Mycoplasma pneumoniae ß-glycolipid antigens for the diagnosis of mycoplasma infectious diseases.

Mycoplasma pneumoniae expresses ß-glycolipids (ß-GGLs) in cytoplasmic membranes, which possess a unique ß(1 → 6)-linked disaccharide epitope, which has high potential in biochemical and medicinal applications. In the present study, a series of ß-GGLs homologues with different acyl chains (C12, C14, C16, and C18) were prepared from a common precursor. An ELISA assay using an anti-(ß-GGLs) monoclonal antibody indicated that the synthetic homologues with long acyl chains had greater diagnostic potential in the order C18 > C16 > C14 > C12. Toward a simultaneous detection of natural glycolipids by mass spectrometry (MS), a deuterium-labeled C16 homologue (ß-GGL-C16-d3) was prepared and applied as an internal standard for a high-resolution electrospray ionization MS (ESI-MS) analysis. The ESI-MS analysis was used to identify and quantify acyl homologues (C16/C16, C16/C18, and C18/C18) of ß-GGL-C16 in cultured M. pneumoniae. A ß-GGLs homologue with a 1,2-diacetyl group (C2) was also prepared as a "water soluble" glycolipid homologue and characterized by 1H NMR spectroscopy. We envisage that each of these chemosynthetic homologues will provide promising approaches to solve medical and biological problems associated with mycoplasma infectious diseases (MIDs).

Frustrated Helicity: Joining the Diverging Ends of a Stable Aromatic Amide Helix to Form a Fluxional Macrocycle.

Macrocyclization of a stable two-turn helical aromatic pentamide, that is, an object with diverging ends that are not prone to cyclization, was made possible by the transient introduction of disruptors of helicity in the form of acid-labile dimethoxybenzyl tertiary amide substituents. After removal of the helicity disruptors, NMR, X-ray crystallography, and computational studies show that the macrocycle possesses a strained structure that tries to gain as high a helical content as possible despite being cyclic. Two points of disruption of helicity remain, in particular a cis amide bond. This point of disruption of helicity can propagate along the cycle in a fluxional manner according to defined trajectories to produce ten degenerate conformations.

Synthesis and Optical Properties of Excited-State Intramolecular Proton Transfer Active π-Conjugated Benzimidazole Compounds: Influence of Structural Rigidification by Ring Fusion.

Two excited-state intramolecular proton transfer (ESIPT) active benzimidazole derivatives (1 and 2) were synthesized by acid-catalyzed intramolecular cyclization. The steady-state fluorescence spectrum in THF revealed that ring-fused derivative 1 exhibits a dual emission, namely, the major emission was from the K* (keto) form (ESIPT emission) at 515 nm with a large Stokes shift of 11 100 cm-1 and the minor emission was from the E* (enol) form at below 400 nm. In contrast, the normal emission from the E* form was dominant and the fluorescence quantum yield was very low (Φ âˆ¼ 0.002) for nonfused derivative 2. The time-resolved fluorescence spectroscopy of 1 suggested that ESIPT effectively occurs due to the restricted conformational transition to the S1-TICT state, and the averaged radiative and nonradiative decay rate constants were estimated as ⟨kf⟩ = 0.15 ns-1 and ⟨knr⟩ = 0.60 ns-1, respectively. The fluorescence emission of 1 was influenced by the measurement conditions, such as solvent polarity and basicity, as well as the presence of Lewis base. The ESIPT process and solvatochromic behavior were nicely reproduced by the DFT/TDDFT calculation using the PCM model. In the single-crystal fluorescent spectra, the ESIPT emissions were exclusively observed for both fused and nonfused compounds as a result of hydrogen-bonding interactions.

Formation of Benzimidazoisoquinolinium and Benzimidazoisoindolinum Cyclic Systems by the Reaction of 2-(2-Alkynylphenyl)benzimidazoles with Iodine and Iodine-Iodine Interaction Including Halogen Bonding in Their Crystal Structures.

The reaction of 2-(2-alkynylphenyl)benz[d]imidazoles with molecular iodine constructed 5- and 6-membered rings as novel organic salts in high yield. The constituted number of ring systems was influenced by the substituent at the triple bond: 6-membered rings were formed from compounds bearing aryl substituents, whereas 5-membered ones were obtained from compounds with hydrogen or alkyl substituents. The products were obtained with triiodide as a counteranion; however, compounds with iodide were also obtainable under certain conditions. We also revealed that they had an iodine-iodine interaction included in halogen bonding between an iodo moiety of the cation and a triiodide or iodide of the counteranion. The iodine-iodine interaction was formed with greater preference than the electrostatic interaction between the cationic atom and triiodide or iodide.

Cerasoidine, a Bis-aporphine Alkaloid Isolated from Polyalthia cerasoides during Screening for Wnt Signal Inhibitors.

A new bis-aporphine alkaloid, cerasoidine (1), was isolated from the root extract of Polyalthia cerasoides together with the known bis-aporphine bidebiline E (2) during screening for compounds with Wnt signal inhibitory activities. The structure of cerasoidine (1) was established by X-ray analysis and shown by chiral HPLC analyses and electronic circular dichroism to be a 57:43 mixture of R(-)- and S(+)-atropisomers. Bidebiline E (2) exhibited inhibition of transcriptional activity of TCF/ß-catenin with an IC50 value of 20.2 µM and was also found to inhibit Wnt signaling by decreasing nuclear ß-catenin.

Chiral Bis(imidazolidine)-Derived NCN Pincer Rh Complex for Catalytic Asymmetric Mannich Reaction of Malononitrile with N-Boc Imines.

Chiral bis(imidazolidine)-derived NCN-rhodium complexes ([PhBidine-RhX2 ] and [tBu-PhBidine-RhX2 ]) were prepared by a CH insertion method, and the structures were unequivocally determined by X-ray crystallographic analysis. The [tBu-PhBidine-Rh(OAc)2 ] complex smoothly catalyzed an asymmetric Mannich reaction of malononitrile with N-Boc imines to give products in up to 94 % ee, which are useful for the synthesis of chiral α-amino acids.

BF3-Mediated cis-Selective Cycloaddition of O-Silyloxime with Alkenes.

A C-amide-substituted O-silylated oxime, (E)-(tert-butyldimethylsiloxyimino)acetic acid N,N-dimethylamide (8b), on treatment with 2.2 equiv of BF3·OEt2, in situ generated boracyclic nitrone-type intermediate BF3·14, which underwent cycloaddition with alkenes to give 3,5-cis-isoxazolidines as the major products. The mechanism was strongly supported by isolation of the reaction intermediate 14 that was characterized by X-ray diffraction and its further reaction. This cycloaddition was successfully applied to the synthesis of syn-HPA-12 known as an inhibitor of CERT that mediates the transport of ceramide.

Conformational and Chiral Properties of Cyclic-tri(N-methyl-meta-benzamide) Bearing Amidino Groups.

Cyclic triamides bearing amidino groups at the meta position of the phenyl rings were synthesized, and their conformational properties in the crystal and in solution were examined. Compound exists as a capsule-type dimer of the enantiomers with a bowl-shaped syn conformation in the crystal state. Compound exists mainly in the syn form in solution, and chiral induction was observed upon addition of a chiral acid to a solution of.