Norikazu Miyoshi

A Novel Aqueous Barbier-Grignard-Type Allylation of Aldehydes in a Mg/BiCl3 Bimetal System

Abstract The allylation of aldehydes with allylic bromides proceeded smoothly in a Mg / BiCl 3 bimetal system even in THF-H 2 O to afford the corresponding homoallylic alcohols in good yields.

Enantioselective protonation of samarium enolates by a C2-symmetric chiral diol

Abstract High enantioselectivity (up to 97%ee) have been achieved in the protonation of samarium enolates which were generated by SmI 2 -mediated cross-coupling reaction between unsymmtrical dialkylketene and allyl iodide, using a C 2 -symmetric chiral diol as a proton source. The stereochemistry of enolate formation and of the enantioselective protonation is discussed.

Asymmetric trimethylsilylcyanation of aldehydes utilizing chiral bismuth compounds. A frontier in bismuth mediated synthetic reactions

Bismuth(III) chloride (BiCl3) was found to work efficiently as a versatile catalyst for cyanation of aldehydes with trimethylsilyl cyanide to afford the corresponding cyanohydrins in high yields. Triphenylbismuthan (Ph3Bi) is also effective. The reaction has been applied to the asymmetric cyanation of a variety of aldehydes in high yields with moderate to good enantioselectivities by use of a chiral bismuth catalyst prepared in situ from BiCl3 and (2R,3R)-(+)-diethyl tartrate.

A convenient procedure for bismuth-mediated Barbier-type allylation of aldehydes in water containing fluoride ions

A new and convenient procedure for synthesis of homoallylic alcohols in generally good to excellent yields has been developed. The bismuth-mediated Barbier-type allylation of aldehydes (aromatic, aliphatic, alicyclic and heterocyclic) with allyl bromide has been carried out smoothly in water in the presence of fluoride ions.

Effects of triphenyltin on growth and viability of K562 leukemia cells

The effects of triphenyltin on growth and viability of K562 human leukemia cells were examined using a flow cytometer with fluorescent dyes, ethidium bromide, fluo-3-AM, and propidium iodide. Triphenyltin at concentrations ranging from 30 nM to 1 μM inhibited the growth of K562 cells in a dose-dependent manner when the cells were incubated with triphenyltin at respective concentrations for 72 h. Triphenyltin at 100 nM slowed the rate of growth without affecting the viability. Triphenyltin at 300 nM or higher greatly decreased the viability of K562 cells. Triphenyltin at 300 nM increased the concentration of intracellular Ca(2+) and induced cell cycle arrest in G2/M phase and apoptosis in K562 cells. The concentration of triphenyltin inducing 50% inhibition of growth of K562 cells was lower than those of cisplatin, diphenyltin, monophenyltin, triethyltin and trimethyltin. However, tributyltin was equally toxic. Results suggest that there are several types of mechanisms for the inhibitory action of triphenyltin on the growth of K562 cells, being dependent on its concentration.

ASYMMETRIC SYNTHESIS OF A PIPERAZINE ALKALOID

A piperazine alkaloid, (2S,5S)-2,5-dibenzyl-1,4-dimethylpiperazine, was synthesized by reduction of (3S,6S)-3,6-dibenzyl-1,4-dimethyl-2,5-piperazinedione which was prepared by a catalytic asymmetric hydrogenation of the corresponding 3,6-dibenzylidene derivative.

Methylmercury toxicity in dissociated rat brain neurons: modification by l-cysteine and trimethylbenzylmercaptan and comparison with dimethylmercury and N-ethylmaleimide

The effects of methylmercury (MeHg) on dissociated rat cerebellar neurons were compared with those of MeHg conjugated with l-cysteine (MeHg-Cys conjugate), dimethylmercury (DiMeHg), N-ethylmaleimide (NEM) and ionomycin using a flow cytometer and two fluorescent dyes, fluo-3-AM and ethidium bromide. The efficacies of MeHg to increase intracellular concentration of Ca(2+) ([Ca(2+)]i) and to decrease cell viability were greatly reduced by conjugating MeHg with l-cysteine. It was not due to a decreased lipophilic property of MeHg-Cys because the conjugation of MeHg with trimethylbenzylmercaptane, a lipophilic substance, also reduced the efficacies. It seems that the reactivity of MeHg to SH-groups is responsible for the MeHg-induced toxicity since NEM increased [Ca(2+)]i and decreased cell viability while DiMeHg did not significantly affect them. However, the toxicity of MeHg was not explained only by the reactivity of MeHg to SH-groups since NEM-induced changes in fluo-3 and ethidium fluorescence were different from MeHg-induced ones. Ionomycin-induced changes in those fluorescence were also different although ionomycin decreased cell viability after increasing [Ca(2+)]i. Therefore, it is suggested that the mechanism of MeHg toxicity is more complicated than those of NEM and ionomycin.

Yttrium decreases the intracellular Zn2+ concentration in rat thymocytes by attenuating a temperature-sensitive Zn2+ influx

Yttrium is used in the production of various electronic devices because the alloy it contains enhances or modifies the properties of other elements. In order to study the cytotoxic action of yttrium, the effect of yttrium chloride (YCl(3)) on the intracellular Zn(2+) level was examined in rat thymocytes using a flow cytometer with FluoZin-3-AM and propidium iodide. The application of YCl(3) significantly decreased the intensity of the FluoZin-3 fluorescence, suggesting a decrease in the intracellular Zn(2+) level or quenching of the FluoZin-3 fluorescence by Y(3+). However, since Y(3+) did not attenuate the FluoZin-3 fluorescence under cell-free conditions, the latter suggestion was ruled out. Rat thymocytes possess a temperature-sensitive membrane pathway that carries Zn(2+) into the cells. The application of YCl(3) attenuated the FluoZin-3 fluorescence augmented by externally applied ZnCl(2) in a concentration-dependent manner. This suggested that Y(3+) inhibited the Zn(2+) influx, resulting in the decrease in the intracellular Zn(2+) level. Yttrium may induce dyshomeostasis of intracellular Zn(2+), leading to some cytotoxic actions.

Some characteristics of membrane Cd2+ transport in rat thymocytes: an analysis using Fluo-3

Although cadmium-induced apoptosis of lymphocytes is one of common features in the immunotoxicity of cadmium, the membrane pathway for intracellular cadmium accumulation is not fully elucidated. To characterize membrane Cd2+ transport of rat thymocytes, the change in intracellular Cd2+ concentration under various conditions was examined by the use of Fluo-3, a fluorescent probe for monitoring the change in intracellular concentration of divalent metal cations. The membrane Cd2+ transport was estimated by the augmentation of Fluo-3 fluorescence induced by bath application of CdCl2. Lowering temperature strongly suppressed the augmentation of Fluo-3 fluorescence by CdCl2, suggesting that the metabolic process can be involved in membrane Cd2+ transport. External acidification (decreasing pH) and membrane depolarization by adding KCl attenuated the augmentation, indicating the requirement of electrochemical driving force for membrane Cd2+ transport into the cells. Bath application of CaCl2 and ZnCl2 equally decreased the augmentation, suggesting their competition with Cd2+ at the membrane transport. The augmentation by CdCl2 was lesser in the cells treated with N-ethylmaleimide inducing chemical depletion of cellular thiols. The result suggests the contribution of sulfhydryl groups to membrane Cd2+ transport. Taken together, it is suggested that the cells possess a temperature-sensitive membrane Cd2+ pathway, driven by electrochemical gradient of Cd2+ and transmembrane potential, with competitive binding site. Based on the characteristics described above, it is unlikely that the membrane Cd2+ transport in rat thymocytes is attributed to a single transport system although it has characteristics that are similar to those of divalent cation transporter 1.