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This work reports an operationally convenient ∼20 g scale synthesis of (S)-2-amino-5,5,5-trifluoropentanoic acid and its Fmoc-derivative via dynamic kinetic resolution of the corresponding racemate.

Here we report the first large‐scale synthesis of Fmoc‐(S)‐2‐amino‐6,6,6‐trifluorohexanoic acid via asymmetric alkylation of chiral Ni(II)‐complex of glycine Schiff base with CF3(CH2)3I. The synthesis was performed on over 100 g scale and can be recommended as the most advanced procedure for reliable preparation of large amounts of enantiomerically pure Fmoc‐(S)‐2‐amino‐6,6,6‐trifluorohexanoic acid for protein engineering and drug design. Chiral auxiliary used in this protocol can be >90 % recovered and reused.

An advanced process for large scale (500 g) preparation of a (3Z,5Z)-2,7-dihydro-1H-azepine-derived chiral tridentate ligand (Hamari ligand), widely used for asymmetric synthesis of tailor-made α-amino acids via the corresponding glycine Schiff base Ni(II) complex, is disclosed. The process includes amidation, bis-alkylation, and precipitation/purification of the target compound by TFA as a counterion.

Unusual amino acids are of crucial importance to the synthesis of bioactive peptides and new chemical entities. Innovative methodology is always needed for the preparation of enantiomerically pure amino acids that does not rely on tedious resolution procedures. The proline-derived ligands (R)- and (S)-N-(2-benzoyl-4-chlorophenyl)-1-(3,4-dichlorobenzyl)pyrrolidine-2-carboxamide are outstanding, versatile, and recyclable reagents for the synthesis of tailor-made α- and β-amino acids. Here we report initial studies of the scale-up synthesis of the HCl salt of these reagents on the 100 g scale. The results demonstrate an increased efficiency and environmental friendliness of the bench-scale procedure and provides a firm foundation for the manufacture on multikilogram and larger scales.

Here we report the first large‐scale synthesis of Fmoc‐(S)‐2‐amino‐6,6,6‐trifluorohexanoic acid via asymmetric alkylation of chiral Ni(II)‐complex of glycine Schiff base with CF3(CH2)3I. The synthesis was performed on over 100 g scale and can be recommended as the most advanced procedure for reliable preparation of large amounts of enantiomerically pure Fmoc‐(S)‐2‐amino‐6,6,6‐trifluorohexanoic acid for protein engineering and drug design. Chiral auxiliary used in this protocol can be >90 % recovered and reused.

In this work we report a convenient asymmetric synthesis of Fmoc-(S)-6,6,6-trifluoro-norleucine via alkylation reaction of chiral glycine equivalent. The target amino acid of 99% enantiomeric purity was prepared with 82.4% total yield (three steps).

A stationary phase with a dipole interaction was synthesized by immobilizing the 2,4-dibromophenoxy (DBP) group onto a hydrophilic base resin. The chromatographic properties for halogenated benzenes were evaluated on the DBP-resin by reversed phase mode. The separation efficiency of the DBP-resin for p-xylene and 1,4-dihalogenated benzenes was better than that of the column packed with octadecylsilane (ODS). The results suggested that the retention of the solutes on the DBP-resin depends on the Debye interaction in addition to with the dispersion force caused by the DBP group.

The possibility of using exhaled breath as a substitute for blood/plasma in areas of therapeutic drug monitoring was investigated. Theophylline was used as a model chemical of non-volatile drugs and the adsorbents suitable for drug capture from exhaled breath were studied. Two macro-porous adsorbents with different monomer compositions were prepared by suspension copolymerization. The capture properties of the synthesized adsorbents and two conventional gas adsorbents packed in a cartridge were evaluated by both aerosol generation and rat expiration. The efficiency of drug capture did not improve by decreasing the pore size and by increasing the specific surface area. A hydrophilic region was found to be necessary for holding the aerosol particles on the adsorbent surface, but a hydrophobic region is also necessary for the adsorption of theophylline. The materials were applied to the intravenous bolus experiment of rats. The amount of theophylline collected from exhaled breath was in the range of 0–0.02 ng min−1, and it varied similarly to the concentration in blood, which was in the range of 0–37 μg mL−1.

Various volatile organic compounds (VOCs) in breath exhaled by patients with lung cancer, healthy controls, and patients with lung cancer who underwent surgery for resection of cancer were analyzed by gas condenser-equipped gas chromatography-mass spectrometry (GC/MS) for development of an exhaled breath monitoring prototype system involving metal oxide gas sensors, a gas condenser, and gas chromatography columns. The gas condenser-GC/MS analysis identified concentrations of 56 VOCs in the breath exhaled by the test population of 136 volunteers (107 patients with lung cancer and 29 controls), and selected four target VOCs, nonanal, acetoin, acetic acid, and propanoic acid, for use with the condenser, GC, and sensor-type prototype system. The prototype system analyzed exhaled breath samples from 101 volunteers (74 patients with lung cancer and 27 controls). The prototype system exhibited a level of performance similar to that of the gas condenser-GC/MS system for breath analysis.

Direct precipitation of nanometer-sized particles of ceria–zirconia (CeO2–ZrO2) solid solutions with cubic and tetragonal structures was successfully attained from acidic aqueous solutions of cerium(III) nitrate (Ce(NO3)3) and zirconium oxychloride (ZrOCl2) through the addition of ammonium peroxodisulfate ((NH4)2S2O8), because of promotion of the hydrolysis via the oxidation of Ce3+ ions, together with the simultaneous hydrolysis of ZrOCl2 under hydrothermal conditions. Ultrafine CeO2 particles also could be formed from relatively concentrated aqueous solutions of the same trivalent cerium salt in the presence of (NH4)2S2O8 via hydrolysis. The crystallite size and lattice strain of as-precipitated solid solutions varied, depending on the composition within the CeO2–ZrO2 system. Creation of a solid solution of ZrO2 into a fluorite-type CeO2 lattice clearly introduced lattice strain, as a consequence of the decreasing crystallite size. Both the direct precipitation process and the effectiveness of the presence of (NH4)2S2O8 for the synthesis of CeO2–ZrO2 solid solutions were discussed.

Nanometer-sized particles ranging from 2 to 3 nm of CeO{sub 2} (ceria)-ZrO{sub 2} (zirconia) solid solutions with cubic and/or tetragonal fluorite-type structure in the wide composition range from 20 to 100 mol% CeO{sub 2}, without a trace of monoclinic ZrO{sub 2} phase, could be directly synthesized at low temperature of 100 C from acidic aqueous solutions of ZrOCl{sub 2} and (NH{sub 4}){sub 2}Ce(NO{sub 3}){sub 6} by forced simultaneous hydrolysis, i.e., ''forced cohydrolysis.'' Analytical values of CeO{sub 2}/ZrO{sub 2} ratio in the as-precipitated solid solutions showed fairly good agreement with starting compositions in the solutions. The proceeding of the hydrolysis and formation rate of fluorite-type solid solutions tended to slow down at near median composition. Any change in crystalline phase of as-precipitated solid solutions was not observed by powder X-ray diffractometry after heat treatment in air below 1000 C. Ceria-zirconia solid solutions with fluorite structures containing large amount of ZrO{sub 2} maintained high surface area after heat treatment at 1000 C.

(1) Direct precipitation of ceria-zirconia solid solutions containing more than 66.3mol% ZrO2 was successfully achieved under hydrothermal conditions by co-hydrolysis of acidic aqueous solutions of ZrOCl2 and Ce(SO4)2⋅2(NH4)2SO4.(2) The morphology of ceria-zirconia solid solutions obtained was spherical to some extent due to agglomeration of nanometer-sized primary particles.(3) The crystallite size, lattice parameter, and lattice strain of ceria-zirconia solid solutions also changed depending on the composition in the system. The morphology and crystalline phase of the precipitates were greatly influenced by the nature of anion constituent of cerium and zirconium salts.

In the present paper, we propose an H-slit beam which can be effectively utilized to achieve a highly unidirectional deformable structure.The outlines and characteristics of a 3-axis force / torque sensor based on the above proposal is also reported.This sensor can measure very small reaction forces and torques generated by the motions of a robotic manipulator having its degress of freedom in only one plane.For such an application, a sensor structure which accepts no effect of gravitational force on the manipulator is needed.The important point to consider is that the sensor should be sensitive only in the direction of measurement of force / torque, and very stiff in all other directions.To achieve this goal, we propose the H-slit structure as an extension of the parallel beam structure.The idea behind is the formation of a 4-link closed structure, the joints between the links are deformable, hence the strain gauges can be fixed at these positions.By changing the dimensions of links, a variation in sensitivity and directional stiffness is possible, and by changing the dimensions of H-slit, a mechanical over-load protection is also achieved.

Diastereoselective alkylation of ethyl (5 S )-3,6-diethoxy-2,5-dihydro-5-isopropyl-2-pyrazinecarboxylate (5 S )- 3 with alkyl halides was investigated by using NaH and n -BuLi. These alkylated products (2 R ,5 S )- 4b – d were converted to the corresponding α-alkylated serines ( S )- 6b – d .

Diastereoselective aldol-type reactions of ethyl (5 S )-3,6-diethoxy-2,5-dihydro-5-isopropyl-2-pyrazinecarboxylate (5 S )- 3 with achiral aldehydes 8a – d was investigated by using Sn(OSO 2 CF 3 ) 2 – N -ethylpiperizine and MgBr 2 –triethylamine. The reaction with Sn(II) between (5 S )- 3 and aliphatic aldehydes 8a , b proved to be quite different from that with Mg(II). On the other hand, Sn(II)- or Mg(II)-mediated aldol-type reactions of (5 S )- 3 with benzaldehyde 8c and 3-methyl-2-butenal 8d each afforded the same diastereomer as the major product. These aldol products were each converted to the corresponding α-substituted serines 6 and 7 as enantiomerically pure compounds.

Porcine liver esterase (PLE)- or rabbit liver esterase (RLE)-catalyzed hydrolysis of the pro-S ester group of diethyl α-alkyl-α-(benzyloxycarbonylamino)malonates 2a-c afforded (R)-ethyl α-alkyl-α-(benzyloxycarbonylamino)malonates 3a-c each in excellent enatiomeric excess. Enantiodivergent reductions of these acid esters 3a-c readily furnished both the corresponding enantiomeric α-substituted serines (R)- and (S)- 5a-c .

In the present paper, we propose an H-slit beam which can be effectively utilized to achieve a highly unidirectional deformable structure, and the outlines and characteristics of a 3-axis force/torque sensor based on the above proposal is also reported. This force/torque sensor can measure very small reaction forces/torques generated by the motions of a robotic manipulator having its degrees of freedom in only one plane. For such application, a sensor structure which accepts no effect of gravitational force influence on the manipulator's structure, is needed. The important points to consider include that the sensor should be sensitive only in the direction of measurement of force/torque, and very stiff in all other directions. To achieve these goals, we propose the H-slit structure as an extension of the parallel beam structure. The idea behind is the formations of a 4-1ink closed structure; the joints between the links are deformable, so the strain guages are fixed at these positions. By changing the dimensions of links, a variation in sensativity and directional stiffness is possible, and by changing the dimensions of H-slit, a mechanical over-load protection is also achieved.

A new type of optical rotation (OR) detector based on the phase retardation of the first-order diffraction beam has been constructed. The proposed detector responded to only OR properties by eliminating the circular dichroism (CD) effect. Thus, it could measure the optical rotatory dispersion curves in the Cotton band. Although the optical system requires the incident beam in which the phase retardation is 0.5π, the actual retardation was estimated to be around 0.3π. It means that the OR signal intensity can be doubled. Since the proposed detector works over a range of UV wavelengths, there was a compound whose OR signal intensity was higher than the CD signal intensity. The OR detection was superior to CD in stability and in defining the baseline.

Total synthesis of (+)-conagenin, a low-molecular-weight immunomodulator, was achieved based on enantioselective enzymatic reactions followed by chemoselective reductions.

Porcine liver esterase (PLE)- or rabbit liver esterase (RLE)-catalyzed hydrolysis of the pro-S ester group of diethyl α-alkyl-α-(benzyloxycarbonylamino)malonates 2a-c afforded (R)-ethyl α-alkyl-α-(benzyloxycarbonylamino)malonates 3a-c each in excellent enatiomeric excess. Enantiodivergent reductions of these acid esters 3a-c readily furnished both the corresponding enantiomeric α-substituted serines (R)- and (S)- 5a-c .

Diastereoselective aldol-type reactions of ethyl (5 S )-3,6-diethoxy-2,5-dihydro-5-isopropyl-2-pyrazinecarboxylate (5 S )- 3 with achiral aldehydes 8a – d was investigated by using Sn(OSO 2 CF 3 ) 2 – N -ethylpiperizine and MgBr 2 –triethylamine. The reaction with Sn(II) between (5 S )- 3 and aliphatic aldehydes 8a , b proved to be quite different from that with Mg(II). On the other hand, Sn(II)- or Mg(II)-mediated aldol-type reactions of (5 S )- 3 with benzaldehyde 8c and 3-methyl-2-butenal 8d each afforded the same diastereomer as the major product. These aldol products were each converted to the corresponding α-substituted serines 6 and 7 as enantiomerically pure compounds.

Diastereoselective alkylation of ethyl (5 S )-3,6-diethoxy-2,5-dihydro-5-isopropyl-2-pyrazinecarboxylate (5 S )- 3 with alkyl halides was investigated by using NaH and n -BuLi. These alkylated products (2 R ,5 S )- 4b – d were converted to the corresponding α-alkylated serines ( S )- 6b – d .

The enantioselective aldol-type reaction of ethyl 3,6-diethoxy-2,5-dihydro-2-pyrazinecarboxylate ( 1 ) with achiral aldehydes 2a-d was investigated by employing Sn(OSO 2 CF 3 ) 2 -triethylamine in the presence of (−)-sparteine. Not only a stoichiometric amount, but also 0.3 mol equiv. of (−)-sparteine promoted the highly enantioselective aldol-type reaction.

Total synthesis of (+)-conagenin, a low-molecular-weight immunomodulator, was achieved based on enantioselective enzymatic reactions followed by chemoselective reductions.

The β-hydroxy phenylselenides prepared by cleavage of 2,3-anhydropyranosides with sodium phenylselenide were quantitatively transformed into the corresponding allyl ethers. Oxidation of the allyl ethers, followed by thermal elimination and rearrangement, gave C -allylhexosuloses in good yield. Rearrangement of ethers 10a and 10c was especially stereoselective, giving axially oriented C -allylhexosulose derivatives, which were readily epimerized to their equatorial isomers in quantitative yield. In the Claisen rearrangement of the crotyl ether 14c , the chirality of the sugar was transferred to the newly formed asymmetric carbon atom. This procedure provides a convenient method to convert an anhydro sugar into a C -allylhexosulose derivative.

In order to obtain a scope and limitations of the reaction for newly developed tropone synthesis, some substituted 2,3- and 3,4-epoxy-7,7-dihalobicyclo[4.1.0]heptanes have been prepared and treated with several acids. We found that (1) the epoxy-carbons of starting materials should have, at least, one substituent which may stabilize the carbenium ion formed by cleavage of the epoxide with acid, (2) as halogens in the starting materials, bromine is superior to chlorine, (3) use of 20 molar equivalent of TFA to a substrate in chloroform at refluxing temperature or use of each 5 molar equivalent of TCA and water to a substrate in toluene at 100°C is recommended.

Acetylation of 2-C-benzyl-L-ascorbic acid afforded an unexpected enone, 2,6-di-O-acetyl-2-C-benzyl-5-deoxy-D-glycero-hex-4-en-3-ulosono-1,4-lactone (3) of the open form, along with 2,3,5-tri-O-acetyl-2-C-benzyl-L-lyxo-3-hexulosono-1,4-lactone (4) of the closed form.

In order to obtain a scope and limitations of the reaction for newly developed tropone synthesis, some substituted 2,3- and 3,4-epoxy-7,7-dihalobicyclo[4.1.0]heptanes have been prepared and treated with several acids. We found that (1) the epoxy-carbons of starting materials should have, at least, one substituent which may stabilize the carbenium ion formed by cleavage of the epoxide with acid, (2) as halogens in the starting materials, bromine is superior to chlorine, (3) use of 20 molar equivalent of TFA to a substrate in chloroform at refluxing temperature or use of each 5 molar equivalent of TCA and water to a substrate in toluene at 100°C is recommended.

Check valves for checking reverse water flows in drainage systems sometimes make large impacts through their sudden closure caused by accidental cutoff of drain pumps. In order to characterize such phenomena and to find design criteria for impactless check valves, we observed the motion of a check valve and measured its impact acceleration and pressures in the drainage pipe, using a subscale drainage system. Two peaks of impact acceleration were observed; The first one seemed due to collision of the check valve and the valve seat, whereas the second one did due to water column separation and recombination caused by the low pressure during the closure state of the valve. The former can be reduced by adding mass to the check valve and by setting an appropriate valve-seat angle. The latter possibly can be reduced by relaxing the low pressure during the closure. Subsequently, the check valve opened through the water-column recombination impacts and sometimes showed opening-closing oscillation.

Acetylation of 2-C-benzyl-L-ascorbic acid afforded an unexpected enone, 2,6-di-O-acetyl-2-C-benzyl-5-deoxy-D-glycero-hex-4-en-3-ulosono-1,4-lactone (3) of the open form, along with 2,3,5-tri-O-acetyl-2-C-benzyl-L-lyxo-3-hexulosono-1,4-lactone (4) of the closed form.

The title compounds, methyl 5-deoxy-3-C-hydroxymethyl-2,3-O-isopropylidene-β-DL-lyxo-furanoside, and ribofuranoside derivatives were conveniently synthesized via the Birch reduction of 2-methyl-3-furoic acid, and the latter was identified with the sample prepared from D-xylose.

In solution, 6,7-disubstituted 2,4-dibromobicyclo[3.2.1]octanes and their 8-oxa analogs were deduced to exist preferentially in chair conformations of their 6-membered ring by comparing their JVic with those calculated for the conformations obtained by MM2 method. Among them, the 2-exo,4-exo-dibromides on treatment with base gave readily tetracyclo[3.2.1.02,7.04,5]octane derivative and its 3-oxa analog by double 1,3-dehydrobromination.

Small amounts of polycyclic aromatic hydrocarbons (PAHs) in aqueous solution were almost completely adsorbed on barium salts of copper (II) sulphophthalocyanines and cobalt (II) phthalocyanine, which were precipitated from the solution. Recoveries of the PAHs from the precipitates by thermal desorption gas chromatography were 71–95%. The method is useful for the concentration and analysis of medium molecular weight, thermally stable PAHs.

The benzyne reaction of cyclic olefins, in competition with that of cyclohexene has been studied. The relative reactivities for ene reaction and the stereoselectivity of the reaction with 4-t-butylcyclohexene, which afforded trans-5-t-butyl-3-phenylcyclohexene and cis-3-t-butyl-6-phenylcyclohexene, are consistent with the stereochemical requirements along the reaction pathway.

As an effective computational model, a vaporous cavity model, an air release model and a discrete free gas model have been developed to simulate transient cavity flows. In this report, the validity of these models is reexamined by employing a prototype horizontal pipeline with or without elevation points. In the vaporous cavity model and the discrete free gas model, fairly good results are obtained for the case of low void fraction becouse numerical instability appears to be small in the pressure responses using the characteristics method with linear interpolations. The air release model represents satisfactory results in the case of a relatively large void fraction, however such a model includes some unpredictable parameters and requires a more complicated algorithm than the other two models to get a solution. all the models discussed here are able to predict the maximum pressure profile along the pipeline for transient cavity flows up to at least 3% of void fraction.

南極大陸の昭和基地を中心とした地域の土壌から,193株の有芽胞偏性嫌気性菌(clostridia)を分離した.そのうち155株を11菌種に同定できた.C. perfringens, C. bifermentans, およびC. sordelliiの順に多数分離された.C. sporogenes, C. plagarum, C. paraperfringens, C. septicum, C. tertium, C. cadaveris, C. butyricumおよびC. felsineumは少数分離された.人や動物によって汚染され難い地域からもclostridiaが多く検出された.南極土壌中のclostridiaの分布および特徴を日本の土壌と比較した.1)日本の土壌からは検出されてないC. sordelliiおよびC. paraperfringensを南極土壌から多く分離した.2)南極土壌中の菌数分布は好気性菌より嫌気性菌の方が多く,日本の土壌と逆であった.3)抗生剤の感受性試験のうち, tetracycline系に対して南極土壌からのclostridiaは,対照菌株に比してより感受性であった., From the soil in the area around Syowa Station, East Ongul Island, Antarctica, 193 strains of clostridia were isolated and identified. It was interesting that many clostridia were contained in the soil samples taken from the places which were considered to be scarcely contaminated by human beings and animals. One hundred and fifty-five strains were assigned to 11 species, and C. perfringens, C. bifermentans and C. sordellii were isolated frequently, while C. sporogenes, C. plagarum, C. paraperfringens, C. septicum, C. tertium, C. cadaveris, C. butyricum and C. felsineum less frequently. The peculiar distribution and characteristics of the clostridia in the Antarctic soil were discussed in comparison with those found in the soil in Japan. 1) C. sordellii and C paraperfringens were never isolated from the soil in Japan. 2) Distribution of aerobes was less extensive than anaerobes in the Antarctic soil. 3) To the tetracycline group among antibiotics tested, the Antarctic strains were more susceptive than the control (Japan) strains.

The photolysis of (1S)-exo-1-methoxycarbonylmethyl-3-t-butyl-1a,7b-dihydro-1H-cyclopropa[a]naphthalene gave (7S)-5-t-butyl-7-methoxycarbonylmethyl-7H-benzocycloheptene by a 1,5-sigmatropic shift, proving the rearrangement to proceed with the inversion of the configuration of the migrating center.

The photolysis of 1-substituted 1a,7b-dihydro-1H-cyclopropa[a] naphthalenes in the presence of Michler’s ketone leads principally to 5-substituted 5H-benzocycloheptenes as primary products via a stepwise mechanism. The reaction proceeds smoothly with inversion of the migrating carbon if there is no steric hindrance, but it proceeds predominantly with retention if the inversion course is severely suppressed by steric hindrance. The marked difference in the exo-endo ratio of the secondary photocyclization products depending on the irradiation conditions was also recognized for 1-methoxycarbonylmethyl derivative.