Construction of the taxane skeleton via the stereoselective conjugate addition of cyanide and the intramolecular B-alkyl Suzuki-Miyaura coupling reaction

Construction of the taxane skeleton via the stereoselective conjugate addition of cyanide and the intramolecular B-alkyl Suzuki-Miyaura coupling reaction is described. A conjugate addition of cyanide to enone 17 proceeded diastereoselectively to provide the desired 18 incorporating the correct C3 stereogenic center in the taxol C-ring. The intramolecular B-alkyl Suzuki-Miyaura coupling reaction of 22, which was derived from 18, successfully furnished the taxol B-ring in 81% yield.     

Development of a column-switching high-performance liquid chromatography for kynurenine enantiomers and its application to a pharmacokinetic study in rat plasma

Kynurenine (KYN), a tryptophan metabolite, is a precursor of kynurenic acid, which is an antagonist of N-methyl-d-aspartate receptor. In this study, an enantiomeric separation of d,l-KYN derivatized with the benzofurazan fluorescence reagent 4-N,N-dimethylaminosulfonyl-7-fluoro-2,1,3-benzoxadiazole (DBD-F) (DBD-d,l-KYN) was first investigated by using a high-performance liquid chromatography (HPLC) with several chiral columns. As a consequence, DBD-d,l-KYN was enantiomerically separated on a cellulose-type chiral column (CHIRALCEL OJ-RH) with a mobile phase of H₂O/CH₃CN/MeOH (40/50/10) containing 0.1% acetic acid. Under this condition, the separation factor and resolution were 1.48 and 1.28, respectively. Next, a column-switching HPLC consisting of both octadecylsilica and chiral columns was developed and used to determine both d- and l-KYN enantiomers in 10 μL of rat plasma following the intraperitoneal administration of d,l-KYN to rats (10 mg kg⁻¹). The result revealed that the concentration of l-KYN was higher than that of d-KYN, suggesting that d-KYN was eliminated faster than l-KYN.     

Synthesis and biological activities of novel furo[2,3,4-jk][2]benzazepin-4(3H)-one derivatives

A novel seven-membered lactam formation method has been established by intramolecular ring closure reaction of 4-bromo-(E)-3-[(2-alkylvinyl)carbonylamino]benzo[b]furans under Heck coupling conditions. A number of furo[2,3,4-jk][2]benzazepin-4(3H)-ones, tricyclicbenzo[b]furans, have been prepared by this method and evaluated for their leukotriene B(4) (LTB(4)) receptor and poly(ADP-ribose)polymerase-1 (PARP-1) inhibitory activities.     

Comprehensive interpretation of a substitution effect on an order-disorder phase transition in A(1-x)MxW2O(8-y) (A = Zr, Hf; M = trivalent cations) and other ZrW2O8-based solid solutions

Hf(1-x)Lu(x)W(2)O(8-y) solid solutions up to x = 0.04, based on a negative thermal expansion material HfW(2)O(8), were synthesized by a solid state reaction method. X-ray diffraction experiments of these solid solutions from 90 to 560 K indicated thermal contraction with increasing temperature. Temperatures of order-disorder phase transition (T(trs)) associated with the orientation of WO(4) tetrahedra were determined from disappearance of a characteristic diffraction peak (310). The T(trs) of the solid solutions drastically decreased with increasing Lu content. Saturated order parameters (eta(s)) associated with the orientational order of the WO(4) pairs were estimated from the characteristic diffraction peak at sufficient low temperature. These behaviors of Hf(1-x)Lu(x)W(2)O(8-y) are consistent with those of Zr(1-x)M(x)W(2)O(8-y) (M = Sc, Y, In, Lu). The drastic suppression of T(trs) in Hf(1-x)Lu(x)W(2)O(8-y) can be interpreted in the framework of a model proposed for Zr(1-x)M(x)W(2)O(8-y), which states the existence of a local nanoregion including the WO(4) pairs having the frozen-in orientational disorder. To understand the substitution effect on the order-disorder phase transition comprehensively, classification based on the saturated order parameter eta(s) of the phase transition of AW(2)O(8) (A = Hf, Zr)-based solid solutions was carried out and discussed.     

Temperature‐sensitive poly(N‐isopropylacrylamide)‐grafted surfaces modulate blood platelet interactions

Interactions between a temperature‐responsive poly(N‐isopropylacrylamide)‐grafted surface and blood platelets have been analyzed with computerized image analysis. Platelet behavior on this surface is dramatically dependent upon temperature in contrast to that on poly(ethylene glycol) (PEG)‐grafted surfaces or polystyrene. The poly(N‐isopropylacrylamide)‐grafted surface interacts with platelets similarly as the poly(ethylene glycol)‐rafted surface at 18°C. At 37°C, platelets readily adhere onto the poly(N‐isopropylacrylamide)‐grafted surface similarly as to that of polystyrene.     

Rheological properties of linear and crosslinked polymer blends: Relation between crosslink density and enhancement of elongational viscosity

Strain‐hardening behavior in the elongational viscosity of binary blends composed of a linear polymer and a crosslinked polymer, in which the molecular chains of the linear polymer were incorporated into the network chains of the crosslinked polymer, was studied. Blending the crosslinked polymer characterized as the gel just beyond the sol–gel transition point greatly enhanced the strain‐hardening behavior in the elongational viscosity, even though the amount of the crosslinked polymer was only 0.3 wt %. However, the crosslinked polymer, which was far beyond or below the sol–gel transition point, had little influence on the elongational viscosity as well as the shear viscosity. The stretching of the chain sections between the crosslink points was responsible for the strain‐hardening behavior. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 228–235, 2001     

Structure and mechanical properties for binary blends of polypropylene and ethylene‐1‐hexene copolymer

The structure and mechanical properties of the injection‐molded products for the binary blends composed of an isotactic polypropylene (PP) and a rubbery ethylene‐1‐hexene copolymer (EHR) were studied. The following two types of blends were employed: one is the incompatible blend of PP and ethylene‐rich EHR; the other is the compatible blend of PP and 1‐hexene‐rich EHR. The incompatible blend shows a phase‐separated morphology, in which EHR domains in the skin layer highly orient to the flow direction. On the other hand, the compatible blend shows fairly homogeneous morphology in the skin and core regions, in which EHR molecules are dissolved into the amorphous PP region. The measurements of birefringence and infrared dichroism revealed that the magnitude of molecular orientation along the flow direction for the compatible blend is larger than that for the incompatible blend. Nevertheless, it was also found that anisotropy of the mechanical properties for the compatible blend is less prominent, which is attributed to lack of the mechanical connection between neighbor crystalline fragments aligned perpendicular to the flow direction. © 1999 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 37: 701–713, 1999