Diphenylprolinol Silyl Ether as a Catalyst in an Enantioselective,Catalytic Michael Reaction for the Formation of α,α‐Disubstituted α‐Amino Acid Derivatives

Direct and enantioselective : Diphenylprolinol silyl ether was found to catalyze the direct, asymmetric Michael reaction of 4‐substituted 2‐aryl‐2‐oxazoline‐5‐one and α,β‐unsaturated aldehydes, affording the chiral α,α‐disubstituted α‐amino acid derivatives with excellent enantioselectivity.

     

Scheduling of corrugated paper production

Corrugated paper is produced by gluing three types of papers of the same breadth. Given a set of orders, we first assign each order to one of the standard breadths, and then sequence those assigned to each standard breadth so that they are continuously manufactured from the three rolls of the specified standard breadth equipped in the machine called corrugator. Here we are asked to achieve multi-goals of minimizing total length of roll papers, total loss of papers caused by the differences between standard breadths and real breadths of the orders, and the number of machine stops needed during production. We use integer programming to assign orders to standard breadths, and then develop a special purpose algorithm to sequence the orders assigned to each standard breadth. This is a first attempt to handle scheduling problems of the corrugator machine.     

Evaluation of intrinsic compressibility of proteins by molecular dynamics simulation

Molecular dynamics simulation has been performed on five native proteins in water to evaluate their intrinsic isothermal compressibilities beta(T,int). To identify physical factors contributing to protein compressibility, a general method is presented for analyzing the compressibility of mechanically inhomogeneous systems. The value of beta(T,int) varies with protein species considerably: beta-lactoglobulin (14.15 x 10(-2) GPa(-1)) is more than twice as compressible as ribonuclease A (6.77 x 10(-2) GPa(-1)). Beta-lactoglobulin and myoglobin (13.95 x 10(-2) GPa(-1)) have similar values of beta(T,int), but the mechanisms responsible for them are significantly different. The volume fluctuations of internal cavities and the magnitudes of the crosscorrelation between them are the key factors determining beta(T,int) of proteins. Though the volume fractions of internal cavity for the five studied proteins are nearly equal to one another, the mean cavity compressibilities beta(T,cav) vary considerably with protein species and range from 0.35 to 0.69 GPa(-1), which are much smaller than those of normal organic liquids such as methanol, ethanol, and benzene and close to that of glycerol (0.55 GPa(-1)), a strongly associated liquid.     

Langmuir monolayer properties of the fluorinated-hydrogenated hybrid amphiphiles with dipalmitoylphosphatidylcholine (DPPC)

Surface pressure–area (π–A), surface potential–area (ΔV–A), and dipole moment–area (μ–A) isotherms were obtained for the Langmuir monolayer of two fluorinated-hydrogenated hybrid amphiphiles (sodium phenyl 1-[(4-perfluorohexyl)-phenyl]-1-hexylphosphate (F6PH5PPhNa) and (sodium phenyl 1-[(4-perfluorooctyl)-phenyl]-1-hexylphosphate (F8PH5PPhNa)), DPPC and their two-component systems at the air/water interface. Monolayers spread on 0.02 M Tris buffer solution (pH 7.4) with 0.13 M NaCl at 298.2 K were investigated by the Wilhelmy method, ionizing electrode method and fluorescence microscopy. Moreover, the miscibility of two components was examined by plotting the variation of the molecular area and the surface potential as a function of the molar fraction for the fluorinated-hydrogenated hybrid amphiphiles on the basis of the additivity rule. The miscibility of the monlayers was also examined by construction of two-dimensional phase diagrams. Furthermore, assuming the regular surface mixture, the Joos equation for analysis of the collapse pressure of two-component monolayers allowed calculation of the interaction parameter (ξ) and the interaction energy (−Δ) between the fluorinated-hydrogenated hybrid amphiphiles and DPPC. The observations by a fluorescence microscopy also supported our interpretation as for the miscibility in the monolayer state. Comparing the monolayer behavior between the two binary systems, no remarkable difference was found among various aspects. Among the two combinations, the mole fraction dependence in monlayer properties was commonly classified into two ranges: 0 ≤ X ≤ 0.3 and 0.3 < X ≤ 1. Dependence of the chain length of fluorinated part was reflected for the molecular packing and surface potential.     

Effective disruption of phosphoprotein-protein surface interaction using Zn(II) dipicolylamine-based artificial receptors via two-point interaction

Protein phosphorylation is ubiquitously involved in living cells, and it is one of the key events controlling protein-protein surface interactions, which are essential in signal transduction cascades. We now report that the small molecular receptors bearing binuclear Zn(II)-Dpa can strongly bind to a bis-phosphorylated peptide in a cross-linking manner under neutral aqueous conditions when the distance between the two Zn(II) centers can appropriately fit in that of the two phosphate groups of the phosphorylated peptide. The binding property was quantitatively determined by ITC (isothermal titration calorimetry), induced CD (circular dichroism), and NMR. On the basis of these findings, we demonstrated that these types of small molecules were able to effectively disrupt the phosphoprotein-protein interaction in a phosphorylated CTD peptide and the Pin1 WW domain, a phosphoprotein binding domain, at a micromolar level. The strategy based on a small molecular disruptor that directly interacts with phosphoprotein is unique and should be promising in developing a designer inhibitor for phosphoprotein-protein interaction.     

Nile Red nucleoside: design of a solvatofluorochromic nucleoside as an indicator of micropolarity around DNA

The fluorophore, Nile Red, effectively works as a polarity-sensitive fluorescence probe. We have designed a new nucleoside modified by Nile Red for examining the change in the polarity of the microenvironment surrounding DNA. We synthesized a Nile Red nucleoside (1), formed by replacing nucleobases with Nile Red, through the coupling of a 2-hydroxylated Nile Red derivative and 1,2-dideoxyglycan. This nucleoside showed a high solvatofluorochromicity. The fluorescence of 1 incorporated into DNA was greatly shifted to shorter wavelength by the addition of beta-cyclodextrin. The photophysical function of the Nile Red nucleoside will be a good optical indicator for monitoring the change in the micropolarity properties at a specific site on target sequences with interaction between DNA and DNA-binding molecules.     

Catalytic asymmetric total synthesis of (+)-lactacystin

Total synthesis of (+)-lactacystin, a potent and selective proteasome inhibitor, was accomplished using a catalytic enantioselective Strecker reaction of a ketoimine as the initial key step. An enone-derived N-phosphinoyl ketoimine 7 was selected as a stable masked alpha-hydroxy ketoimine analogue. Excellent enantioselectivity (98% ee) and practical catalyst activity were produced under the optimized catalyst preparation method using 2.5 mol % Gd{N(SiMe3)2}3 as a metal source and 3.8 mol % D-glucose-derived ligand 8. This reaction was conducted on a 5 g scale. The chiral tetrasubstituted C-5 carbon efficiently controlled the stereochemistry of the other three chiral centers of lactacystin. Chelation-controlled Meerwein-type reduction of ketone 5 using i-PrMgBr (originally reported by Kang in a related substrate) selectively produced the desired secondary alcohol at the C-9 position. The C-6 hydroxy and C-7 methyl groups were introduced via a silyl conjugate addition followed by the Tamao oxidation and Donohoe methylation, respectively, in a highly stereoselective manner. A practical amount of enantiomerically pure clasto-lactacystin beta-lactone (2), the biologically active form of (+)-lactacystin, can be synthesized using this route. clasto-Lactacystin beta-lactone (2) was converted to (+)-lactacystin following the reported procedure.     

Relationship between the shape of tibial spurs on X-ray and meniscal changes on MRI in early osteoarthritis of the knee

OBJECTIVE: The purpose of this study was to evaluate the relationship between the shape of tibial spurs on plain X-rays and the meniscal changes on magnetic resonance imaging (MRI) in early osteoarthritis of the knee. MATERIALS AND METHODS: Sixty-three patients (age range, 40 to 59 years; average, 51.8) underwent X-ray and MRI examinations of their knees. Ligament injuries caused by trauma and Kellgren Radiographic Grades III and IV on X-ray were excluded. The shapes of the medial and lateral tibial spurs on X-ray were classified into four types: (a) normal type; (b) horizontal type, in which the spur protruded horizontally; (c) upward type, in which the spur protruded upward; and (d) downward type, in which the spur protruded downward. The femorotibial angle (FTA) on the X-rays was also measured. The medial and lateral meniscal displacement rates on MRI were measured by the proportion by which the meniscal lesion protruded from the edge of the tibial joint surface to the overall meniscal width. The medial and lateral meniscal signal changes on MRI were classified into three types: (a) normal type; (b) intrameniscal type, which showed a high signal within the meniscus; and (c) tear type, which showed a high signal extending to the tibial joint surface. The relationships between the shape of the medial and lateral tibial spur classification on X-ray, the medial and lateral meniscal displacement rates on MRI, the medial and lateral meniscal signal changes on MRI and the FTA were evaluated statistically. RESULTS: Statistically significant correlations were observed between the medial tibial spur classification on X-ray, the medial meniscal displacement rate on MRI and the medial meniscal signal change classification on MRI. In the downward type of medial tibial spur, the medial meniscal displacement rate (50.46+/-17.95%) and the percentage (8 out of 8 cases; 100%) involving the tear type of medial meniscus were greater than the other types. Statistical significance was not observed among the lateral tibial spur classification on X-ray, the lateral meniscal displacement rate on MRI and the lateral meniscal signal change classification on MRI. However, in the horizontal type of lateral tibial spur, the percentage (7 out of 10 cases; 70%) involving the tear type of lateral meniscus was greater than the other types. Correlations tended to be observed between the medial meniscal displacement rate on MRI and the FTA. CONCLUSIONS: In this study, there was a relationship between the shape of the tibial spur on X-ray and the meniscal changes on MRI in early osteoarthritis of the knee. The shape of the medial tibial spur on X-ray can be a useful indicator for predicting the progression of osteoarthritis of the knee. A downward type of medial tibial spur classification on X-ray may be a risk factor for developing severe osteoarthritis of the knee.     

Effect of pre‐treatment of sugarcane bagasse on the cellulose solution and application for the cellulose hydrogel films

Sugarcane bagasse was used as a cellulose resource, and the transparent cellulose hydrogel films were obtained from the purified cellulose by phase inversion process without chemical cross‐linking, when the dissolved cellulose in lithium chloride/N,N‐dimethyl acetamide was transformed into the solid film. On these processes, bagasse was pre‐treated by 10 wt% sodium hydroxide in the absence and presence of bleaching of 10 vol% sodium hypochlorite (NaOCl) solution in order to obtain cellulose fibers. Here, the bleaching temperature was varied from 40 to 50°C. The effect of pre‐treatment conditions on the resultant cellulose solution and hydrogel films was investigated. It was seen that strong bleaching removed most of lignin component from the bagasse. However, viscosity and size exclusion chromatogram of the cellulose indicated that this operation decreased average molecular weight of the cellulose fibers from 2.1 × 10⁶ to 4.8 × 10⁵. These property changes of fibers also caused increase of water content and weakening of mechanical strength of the resultant hydrogels. In addition, scanning probe microscopy in wet state revealed that the porous fiber network structure in the hydrogel was greatly influenced by bleaching with NaOCl. The average pore size of fiber network was decreased from 8.1 to 5.9 nm as the NaOCl treatment was at 50°C, because of expanded fibers in the swollen hydrogel. Copyright © 2016 John Wiley & Sons, Ltd.     

Signal measurement system for intra-body communication using optical isolation method

In this paper, we describe an induced signal measurement on the human body for developing a high-performance transceiver of an intra-body communication system. It is important to isolate awearable transceiver from an electrical instrument for precise measurement. We have developed a probe system using an optical isolation method including a laser diode, photo-diode, and optical fiber. The probe system can be successfully applied to the precise measurement of a receiving signal power at a wearable transceiver. We verify that the experimental results agree with the simulation results based on our previous channel model of intra-body communication.