A photoremovable ligation auxiliary for use in polypeptide synthesis

A photoremovable auxiliary for use in peptide synthesis via the native chemical ligation method is described. A 2-mercapto-1-(2-nitrophenyl)ethylamine (Mnpe-amine) moiety was attached to the N-terminus of a peptide via the periodate oxidation of a seryl peptide. The resulting peptide was then ligated to a peptide thioester, and UV (365 nm) irradiation resulted in the removal of the auxiliary from the peptide.     

A new synthetic method of 3-acyltetronic acid derivatives and its application to the synthesis of isoaspertetronin a (isogregatin A)

A new synthetic method of 3-acyltetronic acid derivatives from the corresponding 3-bromo compound via lithiation with n-BuLi followed either by acylation with acid chloride or better by first reacting with aldehyde and then subsequent oxidation with active MnO₂ is described. A revised structure $\text{10}$ for aspertetronin A(gregatin A) was presented based on the synthesis of the proposed structure $\text{8}$ and spectral comparison of a model compound $\text{12}$ with the natural product.     

Regiocontrolled Syntheses of 3- or 5-Fluorinated Pyrazoles from 2,2-Difluorovinyl Ketones(1)

2,2-Difluorovinyl ketones 1 react with monosubstituted hydrazines to afford 5-fluoropyrazoles in a regioselective manner via replacement of the fluorine by the substituted nitrogen of the hydrazines and dehydration between the carbonyl group of 1 and the NH(2) end. The reactions are successfully effected for both aliphatic and aromatic hydrazines in aqueous ethanol under neutral conditions and in THF under basic conditions with butyllithium, respectively. A similar ring-forming reaction of 1 with hydrazine monohydrate is induced by the addition of trifluoroacetic acid to give N-unsubstituted 3-fluoropyrazoles, which in turn react with alkyl and aryl halides in the presence of sodium hydride, leading to a regiocontrolled synthesis of 3-fluoropyrazoles.     

Reaction of prostacyclin methyl ester with benzenesulfenyl chloride preparation of stable prostacyclin analogs

Several phenyl sulfides including stable 5- and 7-phenylthioprostacyclins were obtained by the reaction of the vinyl ether ($\text{1}$) and prostacyclin methyl ester ($\text{5}$) with PhSCl.     

Dilatometric studies of reaction volumes for the formation of metal complexes in several solvents

A convenient technique is described to determine reaction volumes by means of direct dilatometry. Reaction volumes were determined for the following complexation reactions: formation of monoamminenickel(II) in water (–0.1±0.5 cm³-mol^–1); formation of the 1:1 nickel(II) complex with isoquinoline in methanol and ethanol (3.2±0.1 and 1.1±0.1 cm³-mol^–1, respectively); formation of the 1:1 isothiocyanatoiron(III) complex in water, Me₂SO, and DMF (8.9±0.2, 12.4±0.7, and 25.1±0.3 cm³-mol^–1, respectively); formation of the 18-crown-6 potassium complex in water (10.9±0.2 cm³-mol^–1). We discussed these values in terms of electrostriction and molecular size.     

Synthesis and pharmacological evaluation of novel arylpiperazine derivatives as nonsteroidal androgen receptor antagonists

The search for novel antiandrogens by high-throughput screening (HTS) of the Yamanouchi chemical library led to the discovery of the lead compound (5), which possesses an arylmorpholine moiety. Through the optimization of the lead compound (5), we have found a series of novel arylpiperazine derivatives. Among them, 4-[4-cyano-(3-trifluoromethyl)phenyl]-N-(4-fluorophenyl)piperazine-1-carboxamide (22; YM-92088) exhibited a potent AR antagonistic activity with an IC(50) value of 0.47 microM in the reporter assay, which is more potent than bicalutamide (4) which has an IC(50) value of 0.89 microM.     

Temperature effect on peak width and column efficiency in subcritical water chromatography

Subcritical water has been recently employed as the mobile phase to eliminate the use of organic solvents in reversed-phase liquid chromatography. Although the influence of temperature on retention in subcritical water chromatography has been reported, the temperature effect on peak width and column efficiency has not yet been quantitatively studied. In this work, several polar and chlorinated compounds are separated using pure subcritical water on Zorbax RX-C8, PRP-1 (polystyrene-divinylbenzene), Hypersil ODS, and ZirChrom-polybutadiene columns. Isothermal separations are performed at temperatures ranging from 60 degrees C to 160 degrees C. The retention time and peak width of analytes are reduced with increasing temperature. However, the column efficiency is either improved or almost unchanged with the increasing temperature in the low-temperature range (lower than the 100 degrees C to 120 degrees C range), but it is decreased when temperature is further raised in the high-temperature range (higher than the 100 degrees C to 120 degrees C range). Therefore, a maximum in column efficiency is obtained at temperatures within the 100 degrees C to 120 degrees C range in most cases.     

Application of calorimeters for 5 MeV EB and bremsstrahlung dosimetry

Graphite and water calorimeters, which were developed for use a 10 MeV electron beams (EB) at Riso National Laboratory, were used for process validation and routine dosimeter calibration at a 5 MeV EB. Water calorimeters were used for reference measurements for 5 MeV EB, the response was found to be directly proportional to the beam current and the variation among three water calorimeters was less than ± 2 % in the range of 10 to 40 kGy. CTA, PMMA, RCD dosimeters were calibrated by irradiating the dosimeters and water calorimeters simultaneously. The water calorimeters was proved to be an useful tool at 5 MeV EB. Graphite calorimeters gave reproducible readings within 3.3 % relative errors (95% confidence level) for X-ray measurement.     

Binding methyl orange and hydrophobic fluorescent probes by poly(2-dimethylaminoethyl methacrylate) and copolymers of 2-dimethylaminoethyl methacrylate and N-vinyl-2-pyrrolidone: pH dependence of the binding and fluorescence intensity

The pH dependence of the interaction of poly(2-dimethylaminoethyl methacrylate) and copolymers of 2-dimethylaminoethyl methacrylate and N-vinyl-2-pyrrolidone with methyl orange, 2-p-toluidinylnaphthalene-6-sulfonate (TNS), and 1,6-diphenyl-1,3,5-hexatriene (DHT) was studied by equilibrium dialysis and fluorescence measurements at pH's 7–10. The first binding constant accompanying the binding of methyl orange and TNS by the polymers, in particular the homopolymer, shows a maximum around pH 8 and maximal fluorescence intensity of TNS is obtained around pH 8.5 in the presence of the polymers. To elucidate these observations the pH-induced conformational changes of the homopolymer were examined by potentiometric titration and viscosity measurements and the thermodynamic parameters that accompany the binding were calculated. The polymer was found to change from an extended coil at lower pH to a compact coil at higher pH. The electrostatic attraction between the sulfonate group of the small molecule and the protonated nitrogen atoms on the polymer is increased at lower pH and the hydrophobic interaction between the hydrophobic moieties of the polymer and the small molecule is enhanced at higher pH. The results obtained for the dye binding and fluorescence intensity were discussed in terms of the electrostatic and hydrophobic interactions.     

Thermal decomposition of basic copper carbonate,CuCO3 · Cu(OH)2 · H2O,in carbon dioxide atmosphere (0–50 atm)

The thermal decomposition of basic copper carbonate, CuCO₃ · Cu(OH)₂ · H₂O, was studied by high-pressure DTA under high-pressure carbon dioxide (0–50 atm).The DTA-TG measurement in air showed that the peak temperature was influenced more by heating rate than by sample weight.Decomposition via dehydration and decarbonation was rapidly finished in a single step, and no intermediate was found. The decomposition temperature was strongly influenced by the partial pressure of carbon dioxide. The decomposition temperature increased in the range 0 atm < _Pco2 < 7 atm, but was nearly constant above P_co2 = 7 atm. Explaining these phenomena was approached by various considerations.