Preparation of [Arg-Gly-Asp]-[amino-poly(ethylene glycol)] hybrids and their inhibitory effect on experimental metastasis.

Hybrids of a fibronectin-related tripeptide (Arg-Gly-Asp) and amino-poly(ethylene glycol) were prepared and their inhibitory effect on experimental metastasis in mice was examined. The hybrids exhibited a potent inhibitory effect on the metastasis of B16 melanoma BL6.     

An enzymatically activated fluorescence probe for targeted tumor imaging

Beta-galactosidase is a widely used reporter enzyme, but although several substrates are available for in vitro detection, its application for in vivo optical imaging remains a challenge. To obtain a probe suitable for in vivo use, we modified our previously developed activatable fluorescence probe, TG-betaGal (J. Am. Chem. Soc. 2005, 127, 4888-4894), on the basis of photochemical and photophysical experiments. The new probe, AM-TG-betaGal, provides a dramatic fluorescence enhancement upon reaction with beta-galactosidase, and further hydrolysis of the ester moiety by ubiquitous intracellular esterases affords a hydrophilic product that is well retained within the cells without loss of fluorescence. We used a mouse tumor model to assess the practical utility of AM-TG-betaGal, after confirming that tumors in the model could be labeled with an avidin-beta-galactosidase conjugate. This conjugate was administered to the mice in vivo, followed by AM-TG-betaGal, and subsequent ex vivo fluorescence imaging clearly visualized intraperitoneal tumors as small as 200 microm. This strategy has potential clinical application, for example, in video-assisted laparoscopic tumor resection.     

Novel Mg-responsive fluorescent chemosensor based on benzo-15-crown-5 possessing 1-naphthaleneacetamide moiety

A new fluorescent ionophore for Mg²⁺, 4′-(1-naphthaleneacetamido)benzo-15-crown-5 (1), was synthesized, and its complexation behavior in acetonitrile was investigated by means of UV and fluorescence spectrometry. In the absence of a metal ion, the naphthalene moiety showed quite weak fluorescence emission (fluorescence ‘Off’ state). On the other hand, after the addition of Mg²⁺, fluorescence emission from the naphthalene moiety increased (fluorescence ‘On’ state).     

Total synthesis of broussonetine F: the orthoamide Overman rearrangement of an allylic diol

A first total synthesis of broussonetine F from diethyl L-tartrate was achieved. The cornerstone of our synthesis was an orthoamide Overman rearrangement, which provided an allylic amino alcohol with complete diastereoselectivity.     

Photoexcited chemical wave in the ruthenium-catalyzed Belousov-Zhabotinsky reaction

The excitation of the photosensitive Belousov-Zhabotinsky (BZ) reaction induced by light stimulation was systematically investigated. A stepwise increase in the light intensity induced the excitation, whereas a stepwise decrease did not induce the excitation. The threshold values for the excitation were found to be a function of the initial and final light intensities, time variation in light intensity, and the concentration of NaBrO(3). The experimental results were qualitatively reproduced by a theoretical calculation based on a three-variable Oregonator model modified for the photosensitive BZ reaction. These results suggest that although the steady light irradiation is known to inhibit oscillation and chemical waves in the BZ system under almost all conditions, the stepwise increase in the light irradiation leads to the rapid production of an activator, resulting in the photoexcitation.     

Imidazolium-based chiral ionic liquids: synthesis and application

Synthesis of chiral ionic liquids containing an imidazole nucleus and chiral centers on N-substituents is reported. [(2S,3S)-2,3-Dihydroxybutane-1,4-bis(3-butylimidazolium)]-[bis(trifluoromethanesulfonyl)amide]₂ and [(4S,5S)-2-phenyl-1,3-dioxolane-4,5-bis(1-methylimidazolium)]-[bis(trifluoromethanesulfonyl)amide]₂ induced enantioselectivity in the Michael addition of malonic esters to chalcones.     

Phenylsulfanylation of 3',4'-unsaturated adenosine employing thiophenol-N-iodosuccinimide leads to 4'-phenylsulfanylcordycepin: synthesis of 4'-substituted cordycepins on the basis of substitution of the phenylsulfanyl leaving group

Upon reaction of the 3',4'-unsaturated adenosine derivative 2 with N-iodosuccinimide (NIS) and thiophenol, an unexpected electrophilic hydrophenylsulfanylation proceeded to provide 4'-phenylsulfanylcordycepin 7 in 79% yield with the ratio 7a/7b = 6.6/1. A study of the reaction mechanism revealed that hydrogen iodide (HI) generated from NIS and PhSH acted as an active species. On the basis of a deuterium experiment using PhSD, initial protonation occurred at the β face of the double bond to furnish the β-π complex III, which underwent anti addition of PhSH as a major pathway. Nucleophilic substitution of N(6)-pivaloylated 9 with various alcohols in the presence of N-bromosuccinimide (NBS) gave the respective 4'-α-alkoxycordycepins 15a-21a as the major stereoisomers. Use of DAST in place of an alcohol gave the 4'-α-fluoro analogue 23a stereoselectively. Radical-mediated carbon-carbon bond construction was also applicable to 7, giving 4'-α-allylcordycepin (24a) and 4'-α-cyanoethylcordycepin (25) derivatives.     

Control of photochemistry of stilbazolium ion by adsorption to poly(potassium vinylsulfate) and to hectorite clay

Adsorption or intercalation of trans-1-methyl-4-(2-phenylvinyl)pyridinium ion (stilbazolium ion, SB ( 1 )) to a polyelectrolyte, i. e., poly(potassium vinylsulfate) (PVSK), and to a hectorite clay is studied and its effect on the photochemistry of SB examined. trans-cis Photoisomerization of SB molecularly adsorbed to PVSK proceeds efficiently as with free SB in water, while that of SB molecularly intercalated in the clay is markedly suppressed. Photodimerization proceeds efficiently with SB intercalated in the clay in the aggregated form. Overall photodecoloration, however, proceeds more efficiently with SB adsorbed to PVSK under multiple adsorption conditions apparently due to the higher mobility of PVSK-adsorbed SB compared to that of clay-intercalated SB.