Proposal of a 1-ampere-class deuteron single-cell linac for nuclear transmutation.

A 1-ampere-class high-intensity deuteron linac (ImPACT2017 model) is proposed for mitigating long-lived fission products (LLFPs) by nuclear transmutation. This accelerator consists of single-cell rf cavities with magnetic focusing elements to accelerate deuterons beyond 1 A up to 200 MeV/u.

Diels-alder reaction of 2(1H)-pyridones acting as dienes.

Diels-Alder reactions between N-phenylmaleimide, acting as the dienophile, and 2(1H)-pyridones having a methoxy or a chloro substituent, were carried out, under atmospheric and high pressure conditions, to give the corresponding isoquinuclidine derivatives. Stereoselectivity of the Diels-Alder reactions was studied using molecular orbital calculations.

Regulation of dopamine-induced Na+ current response by small G-protein RhoB or C and phospholipase D in Aplysia neurons.

A family of GTP-binding proteins, Rho, plays critical roles in cell migration, morphological change, cytokinesis, and smooth muscle contraction. Furthermore, evidence has recently been accumulating for an involvement in regulation of receptor-operated ionic channels. We previously reported that stimulation of D1-like receptor by dopamine (DA) induces a slow Na+ current response in the identified neurons of Aplysia under voltage-clamp. To further study a regulatory mechanism of the DA-induced response, we examined possible involvement of small G-proteins and subsequent enzymes. The Na+ current response to DA was gradually and irreversibly depressed after the intracellular injection of either Clostridium difficile toxin B, an inhibitor for all Rho family G-proteins, or Clostridium botulinum C3 exoenzyme, a specific blocker for RhoA-C. Intacellular injection of active RhoA had no significant effect on the response. However, injection of GAP domain of p50RhoGAP significantly depressed the DA-induced response, while application of GEF domain of RhoGEF Dbs increased the response. In addition, either intracellular injection of alpha-synuclein or extracellular application of 1-butanol, inhibitors for phospholipase D (PLD), significantly depressed the DA-induced response. These results suggest that the DA-induced Na+ current response may be facilitated by the activation of Rho family G-protein RhoB or C but not RhoA, and subsequent PLD.

Regulatory roles of Ca2+/calmodulin-dependent protein kinase II and protein phosphatase 2A on the quisqualic acid-induced K+-current response in identified neurons of Aplysia.

In identified B6 neurons of Aplysia buccal ganglia under voltage-clamp, application of quisqualic acid (QA) induces a unique slow K(+)-current response independent of G-protein. The response was augmented by raising the temperature in a similar fashion to the Phe-Met-Arg-Phe-NH(2)-induced K(+)-current response mediated by Gi/o. The QA-induced K(+)-current response markedly increased during the perfusion with Ca(2+)-free solution or after the application of W-7, a calmodulin (CaM) inhibitor. It was also enhanced by intracellular application either of H-7, a serine/threonine protein kinase inhibitor, or of KN-93, a Ca(2+)/CaM-dependent kinase II (CaMKII) inhibitor. Furthermore, the QA-induced response was markedly augmented by pre-treatment with 2,3-butanedione monoxime, an inorganic phosphatase. Intracellular application of protein phosphatase 2A (PP2A) significantly augmented the QA-induced response although neither protein phosphatase 1 nor protein phosphatase 2B altered the response. Application of either okadaic acid or calyculin A, protein phosphatase inhibitors, only slightly depressed the QA-induced response. Surprisingly, W-7 had no augmenting effect on the QA-induced response when examined after the application of either okadaic acid or calyculin A. These results suggest that the K(+)-current response is reciprocally but sequentially regulated by PP2A and CaMKII, the response of which the former is facilitating and the latter is inhibiting.

Reuse of chiral cationic Pd-phosphinooxazolidine catalysts in ionic liquids: highly efficient catalytic asymmetric Diels-Alder reactions.

Chiral cationic palladium-phosphinooxazolidine catalysts in ionic liquid afforded excellent enantioselectivity in Diels-Alder reactions and the catalyst was easily recycled eight times without any significant decrease in chemical yields or enantioselectivity (89-99%, 88-99% ee).

Augmenting effect of serotonin on the voltage-dependent Ca2+ current and subsequently activated K+ current in Aplysia neurons.

Receptor-induced activation of protein kinase C (PKC) plays an important role in modulation of various types of ionic channels in neurons. For example, PKC causes facilitation or long-lasting activation of certain ionic channels involved in spike firing after the receptor stimulation. We investigated the effect of serotonin (5-HT) on the voltage-dependent Ca(2+) channels in RB and RC neurons of Aplysia ganglia under voltage clamp. An outward current response was induced by voltage change of the cell membrane from -60 mV to +10 mV. Application of 5-HT significantly augmented the outward current response to the voltage change. Both the outward current and the augmenting effect of 5-HT markedly decreased when examined in either Ca(2+)-free, 10 mM tetraethylammonium, or 0.3 mM Cd(2+)-solution, indicating the current to be Ca(2+)-activated K(+) current produced by Ca(2+) entry. Intracellular application of either guanosine 5'-O-(2-thiodiphosphate) or cholera toxin (CTX), reagents for G-proteins, irreversibly blocked the augmenting effect of 5-HT. Application of phorbol dibutylate (PDBu), an activator of PKC, augmented the outward current and the effect of 5-HT was occluded after PDBu application. Staurosporine, a specific inhibitor of PKC, markedly suppressed the augmenting effects of both 5-HT and PDBu on the outward current. However, either 5-HT or PDBu did not augment the Ca(2+)-activated K(+) current induced by intracellular injection of Ca(2+) but rather depressed it. These results suggest that stimulation of 5-HT receptor may activate a novel type of CTX-sensitive G-protein and subsequent PKC, and that phosphorylation of voltage-dependent Ca(2+) channels may result in the increase in Ca(2+) entry and subsequent Ca(2+)-activated K(+) current. The mechanism may contribute to retain the long-lasting activation without broadening of the spike width during the excitatory response to 5-HT in these neurons.

Electrophysiological and pharmacological characterization of the K(ATP) channel involved in the K+-current responses to FSH and adenosine in the follicular cells of Xenopus oocyte.

The follicular cells surrounding Xenopus oocyte under voltage clamp produce K(+)-current responses to follicle-stimulating hormone (FSH), adenosine (Ade), and intracellularly applied cAMP. We previously reported that these responses are suppressed by the stimulation of P2Y receptor through phosphorylation by PKC presumably of the ATP-sensitive K(+) (K(ATP)) channel. This channel comprises sulfonylurea receptors (SURs) and K(+) ionophores (Kirs) having differential sensitivities to K(+) channel openers (KCOs) depending on the SURs. To characterize the K(+) channels involved in the FSH- and Ade-induced responses, we investigated the effects of various KCOs and SUR blockers on the agonist-induced responses. The applications of PCO400, cromakalim (Cro), and pinacidil, but not diazoxide, produced K(+)-current responses similar to the FSH- and Ade-induced responses in the magnitude order of PCO400 > Cro >> pinacidil in favor of SUR2A. The application of glibenclamide, phentolamine, and tolbutamide suppressed all the K(+)-current responses to FSH, Ade, cAMP, and KCOs. Furthermore, both the FSH- and Ade-induced responses were markedly augmented during the KCO-induced responses, or vice versa. The I-V curves for the K(+)-current responses induced by Cro, Ade, and FSH showed outward rectification in normal [K(+)](o), but weak inward rectification in 122 mM [K(+)](o). Also, stimulations of P2Y receptor by UTP or PKC by PDBu markedly depressed the K(+)-current response to KCOs in favor of Kir6.1, as previously observed with the responses to FSH and Ade. These results suggest that the K(+)-current responses to FSH and Ade may be produced by the opening of a novel type of K(ATP) channel comprising SUR2A and Kir6.1.

Cyclization of 1-benzyl-1,2-dihydro-2-(substituted methylene)quinolines to pyrrolo[1,2-a]quinoline derivatives.

1-Alkyl-2-alkylthioquinolinium salts were prepared from 1-alkyl-2(1H)-quinolones via 1-alkyl-2(1H)-thioquinolones in two steps. Under mild conditions, the reaction of 1-alkyl-2-alkylthioquinolinium iodides with active methylene compounds in the presence of sodium hydride afforded 1-alkyl-1,2-dihydro-2-(substituted methylene)quinolines in good yields. The cyclization of 1-benzylquinolines using acetic anhydride produced the corresponding pyrrolo[1,2-a]quinoline derivatives.

Synthesis of 5(6H)-phenanthridones using Diels-Alder reaction of 3-nitro-2(1H)-quinolones acting as dienophiles.

Diels-Alder reactions of 3-nitro-2(1H)-quinolones with 1,3-butadiene derivatives were carried out to give the phenanthridone derivatives under both atmospheric and high pressure conditions. Furthermore, the reactivity of 3-substituted 2(1H)-quinolones acting as a dienophile with 2,3-dimethyl-1,3-butadiene was examined using molecular orbital (MO) calculation.

Novel Diels-Alder reaction of 4-nitro-1(2H)-isoquinolones.

A novel Diels-Alder (DA) reaction with 4-nitro-1(2H)-isoquinolones acting as the dienophile afforded 5(6H)-phenanthridone derivatives. The DA reaction of 4-nitro-1(2H)-isoquinolone with 1-methoxy-1,3-butadiene gave biologically active 5(6H)-phenanthridone possessing in a high yield. Regioselectivity of 4-nitro-1(2H)-isoquinolones with 1-methoxy-3-silyloxy-1,3-butadiene was calculated using molecular orbital (MO) calculations.

[Reaction of pyridinium and quinolinium salts having the leaving group at the 2- or 4-position with active methylene compounds].

The reactions of 2- or 4-cyanopyridinium salts with active methylene compounds such as dimethyl malonate, malononitrile, and cyclohexane-1,3-dione affording 2- or 4-(substituted methylene) pyridines are described. Similar reactions of 4-cyano-2-methylthiopyridinium and 4-cyano-2-methylthioquinolinium salts, both of which have two leaving groups, were readily prepared from 4-cyano-1-methyl-2(1H)-pyridone and 4-cyano-1-methyl-2(1H)-quinolone via 4-cyano-1-methyl-2(1H)-thiopyridone and 4-cyano-1-methyl-2(1H)-thioquinolone in two steps, proceeding at the 2- and/or 4-positions on the pyridine or quinoline rings.

[Reaction of pyridinium salts with active methylene compounds].

The carbon-carbon bond-forming reactions of 1-methyl-2-methylthiophenylpyridinium iodides with active methylene compounds (such as dimethyl malonate, malononitrile) using NaH as a base gave the 2-substituted methylene-1,2-dihydropyridine derivatives.

Synthesis of isoquinoline derivatives using ROM-RCM of cyclobutene-yne.

Isoquinoline derivatives were synthesized from cyclobutenylmethylamine derivatives having an alkyne moiety in a tether using a second-generation ruthenium carbene complex under ethylene gas in good yields.

Chiral phosphinooxazolidine ligands for palladium- and platinum-catalyzed asymmetric Diels-Alder reactions.

Cationic palladium (Pd)- and platinum (Pt)-phosphinooxazolidine catalysts 13a-c, 15a-d, 17a-c, and 19a-c were prepared from phosphinooxazolidine ligands 1-3, MCl(2) (M = Pd and Pt), and counterions, and the activities of the catalysts in the asymmetric Diels-Alder (DA) reactions of cyclic or acyclic dienes with imide dienophiles were investigated. These catalysts demonstrated high levels of catalytic activity. The cationic Pd-POZ complex 13c provided particularly excellent enantioselectivity (98% ee) in the DA reactions of cyclopentadiene with acryloyl-, crotonyl-, and fumaroyl-1,3-oxazolidin-2-ones (20a-c).

The small GTP-binding protein RhoA regulates serotonin-induced Na+-current response in the neurons of Aplysia.

Application of serotonin (5-HT) induces a slow inward current response in identified neurons of Aplysia ganglia under voltage clamp. The 5-HT-induced current response was depressed in Na+-free media, but augmented in Ca2+-free media, and unaffected by a change in external K+. The 5-HT-induced response was markedly blocked by intracellular injection of guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS). After the injection of guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS), the responses to 5-HT gradually and significantly increased at the initial period, reached its plateau, and finally decreased. Intracellular injection of Clostridium difficile toxin B, a blocker of small G-protein Rho family members such as Rho (RhoA, RhoB and RhoC), Rac and Cdc42, markedly depressed the 5-HT-induced response. Intracellular injection of Clostridium botulinum C3 exoenzyme, a specific blocker of RhoA, RhoB, RhoC, exhibited a similar depressing effect observed with toxin B. In contrast, intracellular injection of recombinant L63RhoA, a constitutively active form of RhoA, significantly augmented the 5-HT-induced response without affecting the resting membrane. These results suggested that the 5-HT-induced Na+-current response might be facilitated by the activation of Aplysia Rho which is closely homologous to RhoA, RhoB or RhoC in mammalian neuron.

Cycloadditions of 1-substituted 1,3-butadienes with 4- or 3-substituted 2(1H)-quinolones acting as dienophiles.

Cycloadditions of 1,3-butadiene derivatives having an electron-rich group at the 1-position with 4- or 3-substituted 2(1H)-quinolones were carried out to give the richly functionalized phenanthridines under both atmospheric and high pressure conditions. Furthermore, the reactivity of 4- or 3-substituted 2(1H)-quinolones acting as a dienophile with 1-substituted dienes was examined using MO calculation.

Chiral phosphinooxathiane ligands for catalytic asymmetric Diels-Alder reaction.

Chiral cationic palladium[bond]phosphinooxathiane complexes have been found to be effective catalysts for enantioselective Diels-Alder (DA) reaction of cyclopentadiene with acyl-1,3-oxazolidin-2-ones to give the corresponding DA adducts in good yield and high enantioselectivity up to 93% ee.

A novel and efficient chiral palladium-phosphinooxazolidine catalyst for the enantioselective Diels-Alder reaction.

An efficient ruthenium-catalyzed transfer dehydrogenation of amines to imines was acheived under mild conditions using 2,6-dimethoxy benzoquinone (2) or cat. 2/MnO2 as oxidant.

Blockade of ionotropic receptor responses by progesterone in the ganglion cells of Aplysia.

To compare nongenomic effects of progesterone on various receptor responses of neurons, Aplysia ganglion cells were pretreated with 30 microM progesterone for 5 min and various receptor responses were tested using a conventional voltage-clamp method. Progesterone reduced nicotinic receptor-activated Na(+)-currents, nicotinic receptor-activated Cl(-)-currents, gamma-aminobutyric acid receptor-activated Cl(-)-currents, and dopamine receptor-activated Na(+)-currents. These depressant effects are similar at two different agonist concentrations. On the other hand, progesterone affected neither muscarinic receptor-activated K(+)-currents nor dopamine receptor-activated K(+)-currents. The former four types of receptors are known to be ionotropic while the latter two types of receptors are known to be metabotropic. Therefore, progesterone selectively inhibited all the types of ionotropic receptor responses, presumably in a noncompetitive manner.

[Cycloaddition of 1-methyl-2(1H)-quinolones having an electron-withdrawing group at the 3 or 4-position with 1,3-butadiene derivatives].

Cycloaddition of 1-methyl-2(1H)-quinolones with electron-withdrawing groups such as methoxycarbonyl, cyano, and acetyl groups, at the 3 or 4-position with 2,3-dimethoxy- and 2-(trimethylsilyloxy)-1,3-butadienes afforded stereoselectively phenanthridone derivatives under atmospheric and high pressures. Furthermore, regioselectivities of the cycloaddition of 3- or 4-substituted 2 (1H)-quinolones with 2-(trimethylsilyloxy)-1,3-butadiene were examined using MO calculation.