Stereoinvertive C–C Bond Formation at the Boron-Bound Stereogenic Centers through Copper-Bipyridine-Catalyzed Intramolecular Coupling of α-Aminobenzylboronic Esters

Enantiospecific intramolecular Suzuki–Miyaura-type coupling with α-(2-halobenzoylamino)benzylboronic esters to give 3-substituted isoindolinones is achieved by using copper catalysts with 2,2′-bipyridine-based achiral ligands. Enantioenriched α-aminobenzylboron reactants bearing a hydrogen atom at the boron-bound stereogenic carbons undergo stereoinvertive coupling in the presence of a 6-phenyl-2,2′-bipyridine ligand with high enantiospecificity. α-Aminobenzylboronates bearing fully substituted boron-bound stereogenic centers also gave the 3,3-disubstituted isoindolinones with stereospecific stereochemical inversion in the presence of simple 2,2′-bipyridine as a ligand.     

One-Pot Synthesis of Enantioenriched β-Amino Secondary Amides via an Enantioselective [4+2] Cycloaddition Reaction of Vinyl Azides with N-Acyl Imines Catalyzed by a Chiral Brønsted Acid

A catalytic enantioselective synthesis of β-amino secondary amides was achieved using vinyl azides as the enamine-type nucleophile and chiral N-Tf phosphoramide as the chiral Brønsted acid catalyst through a five-step sequential transformation in one pot. The established sequential transformation involves an enantioselective [4+2] cycloaddition reaction of vinyl azides with N-acyl imines as the key stereo-determining step that is efficiently accelerated by a chiral N-Tf phosphoramide catalyst in a highly enantioselective manner in most cases. Further generation of the iminodiazonium ion intermediate through ring opening of the cycloaddition product and subsequent skeletal rearrangement involving Schmidt-type 1,2-aryl group migration followed by recyclization of the resulting nitrilium ion were also initiated by the same acid catalyst. Final acid hydrolysis of the recyclized products in the same pot gave rise to enantioenriched β-amino amides through C−C bond formation at the α-position of the secondary amides.     

Synthesis of C12-Keto Saxitoxin Derivatives with Unusual Inhibitory Activity Against Voltage-Gated Sodium Channels

A novel series of C12-keto-type saxitoxin (STX) derivatives bearing an unusual nonhydrated form of the ketone at C12 has been synthesized, and their Na_V-inhibitory activity has been evaluated in a cell-based assay as well as whole-cell patch-clamp recording. Among these compounds, 11-benzylidene STX ( 3 a ) showed potent inhibitory activity against neuroblastoma Neuro 2A in both cell-based and electrophysiological analyses, with EC₅₀ and IC₅₀ values of 8.5 and 30.7 nm , respectively. Interestingly, the compound showed potent inhibitory activity against tetrodotoxin-resistant subtype of Na_V1.5, with an IC₅₀ value of 94.1 nm . Derivatives 3 a – d and 3 f showed low recovery rates from Na_V1.2 subtype (ca 45–79 %) compared to natural dcSTX ( 2 ), strongly suggesting an irreversible mode of interaction. We propose an interaction model for the C12-keto derivatives with Na_V in which the enone moiety in the STX derivatives 3 works as Michael acceptor for the carboxylate of Asp¹⁷¹⁷.     

Bose-Einstein correlations for pions produced inp p collisions at 360 GeV/c

Zeitschrift für Physik C Particles and Fields - Correlations among identically charged pions were measured for pions produced inp p collisions at 360 GeV/c using the EHS spectrometer. The...     

Dynamic stability of a slender beam under horizontal–vertical excitations

The dynamic stability of a vertically standing cantilevered beam simultaneously excited in both horizontal and vertical directions at its base is studied theoretically. The beam is assumed to be an inextensible Euler–Bernoulli beam. The governing equation of motion is derived using Hamilton's principle and has a nonlinear elastic term and a nonlinear inertia term. A forced horizontal external term is added to the parametrically excited system. Applying Galerkin's method for the first bending mode, the forced Mathieu–Duffing equation is derived. The frequency response is obtained by the harmonic balance method, and its stability is investigated using the phase plane method. Excitation frequencies in the horizontal and vertical directions are taken as 1:2, from which we can investigate the influence of the forced response under horizontal excitation on the parametric instability region under vertical excitation. Three criteria for the instability boundary are proposed. The influences of nonlinearities and damping of the beam on the frequency response and parametric instability region are also investigated. The present analytical results for instability boundaries are compared with those of experiments carried out by one of the authors.     

Controlled Reduction of Carboxamides to Alcohols or Amines by Zinc Hydrides

New protocols for controlled reduction of carboxamides to either alcohols or amines were established using a combination of sodium hydride (NaH) and zinc halides (ZnX₂). Use of a different halide on ZnX₂ dictates the selectivity, wherein the NaH‐ZnI₂ system delivers alcohols and NaH‐ZnCl₂ gives amines. Extensive mechanistic studies by experimental and theoretical approaches imply that polymeric zinc hydride (ZnH₂)_∞ is responsible for alcohol formation, whereas dimeric zinc chloride hydride (H?Zn?Cl)₂ is the key species for the production of amines.     

Konzertierte nukleophile aromatische Substitutionen

Jüngste Entwicklungen in der experimentellen und theoretischen Chemie haben zur Identifizierung einer schnell wachsenden Klasse von nukleophilen aromatischen Substitutionsreaktionen geführt, die einem konzertierten Mechanismus (cS_NAr) folgen, und nicht dem klassischen, zweistufigen S_NAr‐Mechanismus. Während klassische S_NAr‐Reaktionen auf die substantielle Aktivierung des aromatischen Ringes durch elektronenziehende Substituenten angewiesen sind, ist eine solche Aktivierung für den konzertierten Reaktionsverlauf nicht zwingend nötig.     

Calculation of amino acid hydrophilicity indices for retention of peptides on amide, diol and silica columns in normal-phase liquid chromatography

Summary A set of hydrophilicity parameters in a normal-phase liquid chromatography of peptides is presented in order to clarify the contribution of individual amino acid residues to peptide retention and to predict retention times. The retention of 100 peptides was studied using normal-phase liquid chromatography on amide, diol and silica columns. An acetonitrile-water mixed solution containing 0.2% trifluoroacetic acid +0.2% triethylamine was used as the mobile phase in a linear gradient elution system. The contribution of each residue upon retention was calculated by linear multiple regression analysis. This paper described the contribution values as “hydrophilicity retention coefficients”. Using these hydrophilicity retention coefficients, retention times could be predicted for peptides of known amino acid content and sequence. A set of hydrophilicity retention coefficients on each column was successfully explained by contributions to the degree of retention.     

Synthesis of branched polysaccharides by polymerization of 6-O-t-butyldimethylsilyl-D-glucal through stereoregular haloglycosylation

In this letter, we report synthesis of branched polysaccharide 2 by glycosylation of glucal-type monomer 1 with two free hydroxy groups at position 3 and 4. Monomer 1 polymerized with N-halosuccinimide promoter in acetonitrile solvent at room temperature--50 degrees C. The product was isolated as a petroleum ether insoluble fraction. The structure was determined by 1H and 13C NMR spectra as well as elemental analysis to be a polysaccharide consisting of 2-halo-2-deoxy-alpha-D-mannoside units, indicating that the polymerization proceeded via stereoregular glycosylation manner. The molecular weights determined by GPC with DMF were 3,300-4,000. The degree of branching was estimated by the NMR data of the product from the reaction of 2 with 3,5-dinitrobenzoyl chloride.     

Preparation and certification of arsenate [As(V)] reference material, NMIJ CRM 7912-a

Arsenate [As(V)] solution reference material, National Metrology Institute of Japan (NMIJ) certified reference material (CRM) 7912-a, for speciation of arsenic species was developed and certified by NMIJ, the National Institute of Advanced Industrial Science and Technology. High-purity As₂O₃ reagent powder was dissolved in 0.8 M HNO₃ solution and As(III) was oxidized to As(V) with HNO₃ to prepare 100 mg kg^-1 of As(V) candidate CRM solution. The solution was bottled in 400 bottles (50 mL each). The concentration of As(V) was determined by four independent analytical techniques—inductively coupled plasma mass spectrometry, inductively coupled plasma optical emission spectrometry, graphite furnace atomic absorption spectrometry, and liquid chromatography inductively coupled plasma mass spectrometry—according to As(V) calibration solutions, which were prepared from the arsenic standard of the Japan Calibration Service system and whose species was guaranteed to be As(V) by NMIJ. The uncertainties of all the measurements and preparation procedures were evaluated. The certified value of As(V) in the CRM is (99.53 ± 1.67) mg kg^-1 (k = 2).