First total synthesis of (±)-oxerine

Total synthesis of (±)-oxerine (1), a monoterpene alkaloid, starting from 3-bromopyridine (7) is described. The key reaction in this sequence is the samarium iodide (SmI₂)-mediated intramolecular cyclization of γ-ethynyl bromide (4).     

2-Acyloxypyrazines. Convenient acylating agents for amines

2-Acyloxypyrazines were found to be useful acylating reagents for amines. The preference of the acylation was for primary amines rather than secondary ones and also for aliphatic amines rather than aromatic ones.     

Magnetic properties of anhydrous and hydrous modifications of potassium-chloranil salt

The temperature dependence of magnetic susceptibility was studied on the anhydrous and hydrous modifications of the potassium-chloranil salt. While the anhydrous salt exhibits a phase transition at 210–270 K from the low spin state to the high spin state, the hydrous modification shows no such phase transition, and remains in a low spin state over the whole temperature range, 70–300 K.     

Structure-activity relationships of rat neuromedin U for smooth muscle contraction.

Rat neuromedin U (r-NMU) and its fragment peptide amides were synthesized by solid-phase methodology. Using a chicken crop smooth muscle contraction assay, the potency of r-NMU and its fragments relative to porcine neuromedin U-8 (p-NMU-8) was r-NMU: 10.25 +/- 2.88, r-NMU (6-23): 8.01 +/- 1.04, r-NMU (10-23): 2.76 +/- 0.46, r-NMU (13-23): 2.81 +/- 0.52, and r-NMU (16-23): 0.88 +/- 0.19, respectively. Two heptapeptides, r-NMU (17-23) and r-NMU (16-22), had a relative potency of 0.61 and 0.03 respectively, and elicited maximal contraction at a dose of 10 microM to a similar degree to p-NMU-8. The other shorter C-terminal fragments did not elicit the maximal contraction or any activity. In a rat uterus contraction assay, r-NMU (13-23), but not r-NMU (16-23), at a dose of 4 nM retained as high a stimulatory activity as r-NMU itself. r-NMU (17-22) was the smallest peptide fragment to elicit the maximal sustained contraction at 10 microM. These results indicate that the amino acid sequence Phe-Leu-Phe-Arg-Pro-Arg, corresponding to positions 17 to 22 of r-NMU, may be essential for contractile activity. N-terminal peptide segments Tyr-Gln-Gly-Pro corresponding to positions 6 to 9, and Ser-Gly-Gly corresponding to positions 13 to 15, appear to be of special importance for potent activity.     

Construction of an electrochemical DNA chip for simultaneous genotyping of single nucleotide polymorphisms

An electrochemical DNA chip was constructed for simultaneous genotyping of single nucleotide polymorphisms (SNPs) using genomic DNA extracted from blood samples. This chip consisted of electrodes located on a single piece of substrate and allele-specific oligonucleotide probes on the electrodes. As a first application, the 4 SNPs (MxA[-88], MxA[-123], MBL[X/Y], and MBL[A/B]), which have association with the efficacy of interferon therapy for HCV patient, were genotyped on the new DNA chip. Following hybridization of PCR products containing the 4 types of fragments, washing, bisbenzimide H33258 (Hoechst 33258) reaction and electrochemical analyses, 59 blood samples were genotyped by the chip method simultaneously. All procedures were completed within 2 h and the results were 100% concordant with those by the direct sequence method. The electrochemical DNA chip is expected to be a practical tool for SNPs genotyping.     

Synthesis and bioactivity of propranolol analogues with a rigid skeleton. I

The synthesis of two kinds of propranolol analogues, A and B, with a rigid skeleton was investigated. The compounds were designed to help identify the conformation involved in beta-adrenergic receptor-propranolol interaction. The key intermediate, 2-hydroxy.2,3-dihydronaphtho[1,8-bc]pyran (5), was obtained starting from acenaphthenone (1). On sequential dehydration, hydroboration, and oxidation, 5 gave 2,3-dihydronaphtho[1,8-bc]pyran-3-one (8), which was converted to compound A. Compound 5 was also derived to 2-formyl-2,3-dihydronaphtho[1,8-bc]pyran (13) via the 2-vinyl compound (12). Condensation of nitromethane with 13 followed by reduction and alkylation produced the desired compound B. The beta-blocking activities of A and B were examined.     

The electronic structures of charge-transfer complexes: Application of the semiempirical SCF-MO-Cl method

A method is developed to calculate the electronic structure of a molecular complex composed of a -electron donor and a n-electron acceptor. The complex is treated as a single conjugated system of -electrons, and its -electron states are calculated by the semi-empirical SCF-MO-CI method within the n-electron approximation, by including all terms. The method is applied to the TONE complexes of polycyclic aromatic hydrocarbons. It is shown that the absorption spectra of these complexes are well predicted by this method. Discussions are given on the mixing of the charge-transfer configurations and the locally-excited configurations.

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Zusammenfassung Es wird eine Methode entwickelt, um die Elektronenstruktur eines Molekülkomplexes aus einem -Donor and einem n-Akzeptor zu berechnen, and zwar wird er als einheitliches n-Elektronensystem nach einem SCF-Verfahren unter Einschluß aller /3-Terme behandelt. Das Verfahren wird auf TCNE-Komplexe von polycyclischen aromatischen Kohlenwasserstoffen angewendet, wobei sich die Absorptionsspektren recht gut ergeben. Diskutiert wird schließlich noch die Kombination von CI- mit lokal-angeregten Konfigurationen.

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Résumé Développement d'une méthode pour calculer la structure électronique d'un complexe moléculaire entre un donneur et un accepteur d'électrons. Le complexe est traité comme un système conjugué unique dont les états électroniques sont calculés dans l'approximation par la méthode semi-empirique SCF MO CI, en tenant compte de tons les termes. La méthode est appliquée aux complexes des hydrocarbures aromatiques polycycliques avec TCNE. Cette méthode prévoit bien les spectres d'absorption de ces complexes. Discussion du melange des configurations à transfert de charge avec les configurations localement excitées.

     

In vitro enzymatic degradation of nanoparticles prepared from hydrophobically-modified poly(gamma-glutamic acid)

Amphiphilic poly(gamma-glutamic acid) (gamma-PGA) was prepared by the introduction of L-phenylalanine ethylester (L-PAE) as a side chain. This gamma-PGA-graft-L-PAE formed monodispersed nanoparticles in water. The particle size of the gamma-PGA nanoparticles could be controlled by the degree of L-PAE grafting. The hydrolytic degradation and enzymatic degradation by gamma-glutamyl transpeptidase (gamma-GTP) of these gamma-PGA nanoparticles was studied by gel permeation chromatography (GPC) and scanning electron microscopy (SEM). The hydrolysis ratio of gamma-PGA was found to decrease upon increasing the hydrophilicity of the gamma-PGA. The degradation of the gamma-PGA backbone by gamma-GTP resulted in a dramatic change in nanoparticle morphology. With increasing time, the gamma-PGA nanoparticles reduced in size and finally disappeared completely.Time-course of the changes in the morphology of the gamma-PGA nanoparticles following incubation with gamma-glutamyl transpeptidase.     

Oxygen island formation on Pt(111) studied by dynamic Monte Carlo simulation

The formation of oxygen islands on the Pt(111) surface has been studied as a function of temperature by low energy electron diffraction (LEED) experiments and dynamic Monte Carlo (DMC) simulations. By raising the temperature, the (2 x 2) LEED spot intensity increases gradually and decays after a peak at around 255 K (T(p)) with full width of half maximum of 160 K. This behavior is interpreted by DMC simulations with the kinematical LEED analysis. In the DMC simulation, an oxygen atom hops to the neighboring site via the activation barrier of the saddle point. The potential energies at initial, saddle, and final points are changed at each hopping event depending on the surrounding oxygen atoms. By comparing the observed T(p) with the simulated one, the interaction energy E of oxygen atoms on Pt(111) was determined to be 25+/-3 meV at 2a(0). The DMC simulations visualize how the oxygen islands are formed and collapse on Pt(111) with increase of the temperature and well reproduce the surface configurations observed by scanning tunneling microscopy.     

New synthetic method of 1,2-diaryl-1,2-dicarba-closo-dodecaboranes employing aromatic nucleophilic substitution (SNAr) reaction

Aromatic nucleophilic substitution (S_NAr) reaction of 1-phenyl-o-carborane with 4-nitrofluorobenzene in the presence of NaH or KO^tBu proceeded smoothly to give 1-(4-nitrophenyl)-2-phenyl-o-carborane; similar reaction affords various 1,2-diaryl-o-carboranes, which are useful precursors for macromolecular construction and drug design.