Rhodium(I)‐Catalyzed Cycloisomerization of Homopropargylallene‐Alkynes through C(sp3)−C(sp) Bond Activation

Upon exposure to a catalytic amount of [RhCl(CO)₂]₂ in 1,4‐dioxane, homopropargylallene‐alkynes underwent a novel cycloisomerization accompanied by the migration of the alkyne moiety of the homopropargyl functional group to produce six/five/five tricyclic compounds in good yields. A plausible mechanism was proposed on the basis of an experiment with ¹³C‐labeled substrate. The resulting tricyclic derivatives were further converted into the corresponding bicyclo[3.3.0] skeletons with vicinal cis dihydroxy groups.     

Synthesis and biological evaluation of (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acids: a novel series of PPAR gamma agonists

A novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and biologically evaluated. (S)-2-Benzyl-7-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (10, KY-021) was identified as a novel peroxisome proliferators-activated receptor (PPAR) gamma agonist, which showed potent activity in human PPAR gamma (EC50=11.8 nM). KY-021 reduced plasma glucose and triglyceride levels at 3 mg/kg/d for 7 d in male KK-Ay mice. KY-021 also decreased plasma triglyceride levels at 0.3-3 mg/kg/d for 6 d, and improved oral glucose tolerance at 1 and 3 mg/kg/d for 7 d in male Zucker fatty rats. Maximal plasma concentration of KY-021 after oral administration at 10 mg/kg was 6.6 microg/ml and 2.1 microg/ml in male ICR mice and male SD rats, respectively. Repeated oral administration of KY-021 at 30 mg/kg/d for 10 weeks had little toxicity in male SD rats. These results demonstrated that KY-021 has great potential as an efficacious and safe drug for diabetes.     

Development of new-type rapid analysis technology of polychlorinated biphenyls by using liquid chromatographic clean-up material (polyvinyl alcohol gel)

We developed a new-type rapid polychlorinated biphenyl (PCB) analysis technology on the basis of a liquid chromatographic clean-up system combined with a large-volume injection GC-LRMS. Among 18 kinds of materials such as polymer gels, normal-phase silica gels, reversed-phase silica gels, carbon material and ion-exchange material, polyvinyl alcohol (PVA) gel and poly (hydroxylmethacrylate) gel were found to give rather good separation performance for insulating oil. Especially, PVA gel was confirmed to be the most suitable for rapid PCB analysis because of its least required quantity of fraction liquid as well as the highest resolution. Then, we confirmed elution characteristics of all PCB isomers and removal efficiency of insulating oil on PVA gel under an optimized condition, and established high-performance clean-up system using a combination of octadecyl silica gel (ODS), porous graphite carbon (PGC) and PVA gel. In this system, we applied newly valve-switching method that could remove other impurities. In addition, it was demonstrated that the proposed clean-up system could become highly sensitive and rapid PCB analysis technology with 2-h analysis time, lower measurement limit of less than 0.05 mg/kg, and a variation coefficient of less than 5%, by coupling with a large-volume injection type GC-LRMS. Thus, we can conclude that this rapid PCB analysis technology has not only good correlativity (R2>0.999) with standard analysis method but also high durability and can be fully applied to actual PCB-treatment plants.     

Synthesis of Zinc Chlorophyll Homo/Hetero‐Dyads and their Folded Conformers with Porphyrin,Chlorin, and Bacteriochlorin π‐Systems

Zinc complex of pyropheophorbide‐b, a derivative of chlorophyll‐b, was covalently dimerized through ethylene glycol diester. The synthetic homo‐dyad was axially ligated with two methanol molecules from the β‐face and both the diastereomerically coordinating methanol species were hydrogen bonded with the keto‐carbonyl groups of the neighboring chlorin in a complex. The resulting folded conformer in a solution was confirmed by visible, ¹H NMR and IR spectra. All the synthetic zinc chlorin homo‐ and hetero‐dyads consisting of pyropheophorbides‐a, b and/or d took the above methanol‐locked and π–π stacked supramolecules in 1% (v/v) methanol and benzene to give redmost (Qy) electronic absorption band(s) at longer wavelengths than those of the corresponding monomeric chlorin composites. The other zinc chlorin and bacteriochlorin homo‐dyads completely formed similar folded conformers in the same solution, while zinc inverse chlorin and porphyrin homo‐dyads partially took such supramolecules. The J‐type aggregation to folded conformers and the redshift values of composite Qy bands were dependent on the electronic and steric factors of porphyrinoid moieties in dyads.     

Preparation and Crystal Structural Study of a Novel Coordinated Polymer [HgI<Subscript>2</Subscript>(4-bped)<Subscript>2</Subscript>] (bped = bis(4-pyridyl)ethylene diamine)

Abstract  

A novel coordinated polymer [HgI₂(4-bped)₂] was synthesized through the reaction of bis(4-pyridyl)ethylene diamine and HgI₂ in mixed MeOH–THF (5:2). The crystal structural analysis indicated that the complex crystallized in a monoclinic space group P2₁/c, a = 10.8392(12), b = 19.841(2), c = 8.8279(10), β = 95.452(2), V = 1889.9(4) ?³, Z = 4. The complex possessed a novel three-dimensional supramolecular framework formed by hydrogen bonds among repeating [HgI₂(4-bped)]₂ dimeric units.     

Regioselective intramolecular [3+2] annulation of allene-nitrones

The regioselective intramolecular 1,3-dipolar cycloaddition of the phenylsulfonylallene-nitrone derivatives has been developed. This reaction showed that the distal double bond of the allene exclusively reacted with the nitrone group to produce the bicyclic isoxazolidine derivatives regardless of the substitution pattern on the allenyl moiety.     

Use of zeolite to refold a disulfide-bonded protein

Zeolites are microporous crystalline aluminosilicates with a highly ordered structure. Using zeolite beta as an adsorbent, denatured/reduced hen egg lysozyme was refolded to the active form at high concentrations. The denatured/reduced lysozyme was adsorbed onto the zeolite and the protein was refolded by desorbing it into refolding buffer, consisting of redox reagents, guanidine hydrochloride, polyethylene glycol, and L-arginine. This zeolite refolding method could be highly effective for various kinds of proteins, refolding them with high efficiency even when they contain disulfide bonds.