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Imine-bridged pseudorotaxanes can be prepared by forming imine bonds between the diformyl hydrindacene axle and diamino-substituted macrocycles. Such pseudorotaxanes can be used as intermediates for a series of interlocked molecules with multiple rotaxane substructures, since they do not dethread under neutral or basic reaction conditions. Such imine-bridged oligorotaxanes were prepared by connecting the imine-bridged pseudorotaxane using a triethylene glycol spacer followed by introducing end-caps under basic conditions. The resulting oligorotaxanes with different subunit numbers were separated by GPC. The imine-bridged oligorotaxanes are interconvertible with the hydrogen-bonded oligorotaxanes under acidic hydrolyzing conditions by using trifluoroacetic acid. Upon heating the hydrolyzed solution of the oligorotaxane, the imine-bridged oligorotaxane was regenerated since the bridged forms are the thermodynamically favored species. [ABSTRACT FROM AUTHOR]

Liquid crystalline polymers (LCPs) having both hydrophilic and hydrophobic parts are suitable materials for labrication of oriented thin films by the Langmuir-Blodgett (LB) method. In this research, side-chain LCPs with a polyethyleneimine chain and main chain LCPs with a polyoxyethylene chain were used. All of the LCPs formed a monolayer at the air-water interface. Moreover, their multilayered LB films were obtained on solid substrates. The bulk state of the side chain LCPs showed the multilayered structures with the perpendicular alignment of mesogenic groups similar to the LB films. Main-chain LCPs formed folding structures in the layers of the LB films. In the case of LB films of LCPs with azobenzene pendant groups, the initial periodic structures were rebuilt after the irradiation cycles. [ABSTRACT FROM AUTHOR]

This review describes a synthesis of indole compounds using multifunctional synthons. The multifunctional synthons, trienes and gramines, were respectively synthesized using Pd-catalyzed tandem cyclization/cross-coupling reaction of indolylborate with vinyl bromide, and reaction of indolylcuprate with iminium chloride. As an application of the multifunctional synthons to the indole alkaloids synthesis, we accomplished the total synthesis of ellipticine, 9-methoxyellipticine, 9-hydroxyellipticine, tetrahydroellipticine, μ-alkaloid B, μ-alkaloid D, calothrixin A, calothrixin B, tubifoline, and yuehchukene. We have also developed 6π-electrocyclization of hexatrienes catalyzed by Cu(I) trifluoromethanesulfonate toluene complexe, which is unprecedented.

The mammalian circadian pacemaker stays in the paired suprachiasmatic nuclei (SCN). Recent several studies reveal that the circadian rhythms of physiology and behavior are controlled by clock genes. In addition, the effectiveness and toxicity of many drugs vary depending on dosing time associated with 24-h rhythms of biochemical, physiological, and behavioral processes under the control of the circadian clock. Acetaminophen (APAP) is a widely used analgesic drug, and is mainly biotransformed and eliminated as nontoxic conjugates with glucuronic acid and sulfuric acid. Only a small portion of the dose is mainly bioactivated by CYP2E1 to N-acetyl-p-benzoquinone imine (NAPQI), a reactive toxic intermediate. For APAP overdose, glucuronidation and sulfation are saturated and the formation of NAPQI increases. However, the exact mechanisms underlying the chronotoxicity of APAP have not been clarified yet. In the present study, we have clarified that there was a significant dosing time-dependent difference in hepatotoxicity induced by APAP in mice. The mechanism may be related to the rhythmicity of CYP2E1 activity and GSH conjugation. In additon, we investigated whether the liver transcription factor hepatic nuclear factor-1alpha (HNF-1alpha) and clock genes undergoing astriking 24-h rhythm in mouse liver contribute to the 24-h regulation of CYP2E1 activity. A significant 24-h rhythmicity was demonstrated for CYP2E1 activity, protein levels and mRNA levels. HNF-1alpha and clock genes may contribute to produce the 24-h rhythm of CYP2E1 mRNA levels. Metabolism by CYP and GSH conjugation are common metabolic pathways for many drugs such as APAP. These findings support the concept that choosing the most appropriate time of day to administer the drugs associated with metabolic rhythmicity such as CYP and GSH conjugation may reduce hepatotoxicity in experimental and clinical situations. 24-h rhythm of CYP2E1 activity was controlled by HNF-1alpha and clock gene, in a transcriptional level. Identification of rhythmic marker for selecting dosing time will lead improved progress and diffusion of chronopharmacotherapy.

This review describes new syntheses of organofluorine compounds taking advantage of the special properties of fluorine compounds as synthones. The main reactions presented are as follows: 1) Trifluoromethylation of aryl or alkyl halides. Application of this reaction for the synthesis of fluorine analogues of nucleic acid bases is discussed. 2) Some syntheses of trifluoromethyl compounds using the Diels-Alder or the 1,3-dipolar reaction, trifluoromethylated carbene, and photoreaction. 3) The Friedel-Crafts reaction of 3,3,3-trifluoropropene, where linear alkylation occurs due to electronic effect of the trifluoromethyl group in good contrast with the Friedel-Crafts reaction of propene. 4) The ene reaction of trifluoromethylated carbonyl compounds, which work as good enophiles. Application of this reaction to the synthesis of trifluoro analogues of terpenes is discussed. 5) The ene reaction of trifluoromethylated imines. 6) Reaction of halothane, which has a highly acidic hydrogen and two halogens adjacent to the trifluoromethyl group and shows interesting reactivities with various bases and metals to give products with unexpected structures. 7) Reaction of 2-bromo-2,2-difluoroacetate with Cu, where the cross-coupling reaction, Michael-type reaction, and radical reaction for different types of difluoroacetates are presented. 8) Reaction of 2-bromo-2,2-difluoroacetate in the presence of Rh catalyst. This reaction provided a new methodology for the introduction of fluoroalkyl substituents to the alpha-position of alpha,beta-unsaturated ketones. The Rh catalyst solved some difficulties in the introduction of difluoroacetate to carbonyl compounds (Reformatsky reaction). Application of this reaction to imines provided easy access to beta,beta-difluoro-beta-lactams.

This review summarizes the new carbon-carbon bond construction methods based on the radical reaction of imine derivatives. The intermolecular carbon radical addition to oxime ethers proceeded smoothly in the presence of BF3.OEt2. A high degree of stereocontrol in the reaction of oxime ethers was achieved to give amino acid derivatives with excellent diastereoselectivities. The radical reaction of imine derivatives in water has also been investigated. The radical cyclization of oxime ethers proceeded effectively to provide the functionalized heterocycles via a carbon-carbon bond-forming process. These reactions were extended to the solid-phase radical reactions using triethylborane or diethylzinc as a radical initiator.

Some methods for innovative molecular transformations using optically active alpha-amino acids have been exploited. 1) The non-Kolbe reaction of the N-benzoyloxazoline derivative 1 derived from L-serine gave the optically active N,O-acetal 2 when graphite was used an anode material. This reaction represents the first example of "memory of chirality" in the carbenium ion chemistry. 2) The optically active pipecolic acid derivative 13, prepared from L-lysine by using electrochemical oxidation, was cyclopropanated with high diastereoselectivity (96.6%de), and the product 14 was transformed into (2S,3R)-metanopipecolic acid (7). 3) An enantiomerically pure 1,2-dihydropyridine 23 was prepared from L-lysine using electrochemical oxidation as a key step and was utilized as a chiral diene synthon in the Diels-Alder reaction. That is, in the presence of AlCl3, the Diels-Alder reaction between 23 and N-acryloyloxazolidinone 24 gave a cycloadduct with high stereoselectivity, which was converted to an optically active isoquinuclidine derivative 26 (96.8% ee). 4) The Hofmann rearrangement of the L-glutamine derivative 27 to the enantiomerically pure 2-aminobutyric acid derivative 28 was successfully achieved with an electrochemical method using a trifluoroethanol-MeCN solvent system. 5) Some types of N-formyl cyclic amine derivatives were found to be effective activators of trichlorosilane to reduce ketones and imines. Namely, the reduction of ketones and imines by trichlorosilane with a catalytic amount of L-proline derivatives 30 and 32 gave enantiomerically enriched sec-alcohols and amines, respectively, to some extent of optical yields.