Palladium-catalyzed denitrogenation reaction of 1,2,3-benzotriazin-4(3H)-ones incorporating isocyanides

1,2,3-Benzotriazin-4(3H)-ones and 1,2,3,4-benzothiatriazine 1,1(2H)-dioxide reacted with isocyanides in the presence of a palladium catalyst to give 3-(imino)isoindolin-1-ones and 3-(imino)thiaisoindoline 1,1-dioxides, respectively, in high yield. An intermediate azapalladacycle was generated through denitrogenation of the triazine moiety, and an isocyanide was incorporated therein.     

Heterogeneous critical nucleation on a completely wettable substrate

Heterogeneous nucleation of a new bulk phase on a flat substrate can be associated with the surface phase transition called wetting transition. When this bulk heterogeneous nucleation occurs on a completely wettable flat substrate with a zero contact angle, the classical nucleation theory predicts that the free-energy barrier of nucleation vanishes. In fact, there always exists a critical nucleus and a free-energy barrier as the first-order prewetting transition will occur even when the contact angle is zero. Furthermore, the critical nucleus changes its character from the critical nucleus of surface phase transition below bulk coexistence (undersaturation) to the critical nucleus of bulk heterogeneous nucleation above the coexistence (oversaturation) when it crosses the coexistence. Recently, Sear [J. Chem. Phys. 129, 164510 (2008)] has shown, by a direct numerical calculation of nucleation rate, that the nucleus does not notice this change when it crosses the coexistence. In our work, the morphology and the work of formation of critical nucleus on a completely wettable substrate are re-examined across the coexistence using the interface-displacement model. Indeed, the morphology and the work of formation changes continuously at the coexistence. Our results support the prediction of Sear and will rekindle the interest on heterogeneous nucleation on a completely wettable substrate.     

Insoluble polystyrene-bound quaternary onium salt catalysts for the synthesis of cyclic carbonates by the reaction of oxiranes with carbon dioxide

The addition reaction of oxiranes ( 26a—e ) with carbon dioxide (CO₂) was performed using insoluble polystyrene beads containing pendant quaternary ammonium or phosphonium salts as catalysts under atmospheric pressure. The reaction of 26a—e with CO₂ proceeded smoothly catalyzed by 1–2 mol % of the polymer-supported quaternary onium salts to give the corresponding cyclic carbonates ( 27a—e ) in high yields at 80–90°C. In this reaction system, the catalytic activity of the polymer-supported quaternary onium salts was strongly affected by the following factors: degree of ring substitution (DRS) of the onium salt residues to the polymer, degree of crosslinking (DC) of the polystyrene beads, chain length of the alkylene spacer between the polymer back-bone and the onium salt, hydrophobicity of the alkyl group on the onium salts, and kind of onium salts. That is, the polymer-supported quaternary phosphonium salts with low DRS and DC and with long alkylene spacer chain were found to have higher catalytic activity than low molecualr weight quaternary onium salts. The above polymer-supported catalysts can easily be separated at the end of a reaction by filtration and can be reused for at least seven runs. It was also found that the rate of reaction was proportional to the products of catalyst concentration and oxirane concentration. © 1993 John Wiley & Sons, Inc.     

New analytical method for the study of the metabolism of gentiopicroside in rats after oral administration by LC–TOF‐MS following picolinoyl derivatization

The metabolism of gentiopicroside (GPS) in vivo was studied for the first time by LC–MS following picolinoyl derivatization. Incubation of erythrocentaurin, one of the main in vitro metabolites of GPS by intestinal bacteria, with liver microsome indicated that GPS might be metabolized to a final metabolite 3,4‐dihydro‐5‐(hydroxymethyl)isochroman‐1‐one (HMIO) in vivo. After hydrolysis with sulfatase, HMIO was successfully detected in rat plasma after oral administration of GPS by LC–MS following picolinoyl derivatization. 4‐Methoxyphenyl methanol was used as an internal standard to quantify HMIO in rat plasma. A metabolic pathway of GPS in rats is proposed. The monoterpene compound GPS was found to be metabolized to dihydroisocoumarin, which may be responsible for the pharmacological effect of GPS.     

Synthesis, photophysical properties and sugar-dependent in vitro photocytotoxicity of pyrrolidine-fused chlorins bearing S-glycosides

Eight S-glycosylated 5,10,15,20-tetrakis(tetrafluorophenyl)porphyrins (1a′, 1b′, 1a and 1b (a: S-glucosylated, b: S-galactosylated)) and their 1,3-dipolar cycloadducts, i.e. chlorins 2a′, 2b′, 2a and 2b were prepared by nucleophilic substitution of the pentafluorophenyl groups with S-glycoside. These photosensitizers were characterized by ¹H, ¹³C and ¹⁹F NMR spectroscopies and elemental analysis. The photocytotoxicity of the S-glycosylated photosensitizers and the parent porphyrin (1) and chlorin (2) was examined in HeLa cells. Photosensitizers 1, 2, 1a′, 1b′, 2a′ and 2b′ showed no significant photocytotoxicity at the concentration of 0.5 μM, while the deprotected photosensitizers 1a, 1b, 2a and 2b were photocytotoxic. The strong inhibition by sodium azide of the photocytotoxicity of these photosensitizers suggested that ¹O₂ is the main mediator. The S-glucosylated photosensitizers 1a and 2a showed higher photocytotoxicity than S-galactosylated 1b and 2b, respectively. The cellular uptake of 1a and 2a increased up to 24 h, while that of 1b and 2b was saturated by 12 h.     

4-(Pyrrolidinyl)methoxybenzoic acid derivatives as a potent, orally active VLA-4 antagonist

A novel series of benzoic acid derivatives as VLA-4 antagonists were synthesized. Optimization, focusing on activity and lipophilicity needed for cell permeability, resulted in the identification of 15b and 15e with good activity (IC50 = 1.6 nM each) and moderate lipophilicity (Log D = 2.0, 1.8). Furthermore, 15e demonstrated efficacy in murine asthma model by an oral dose of 30 mg/kg.     

Liquid chromatographic analysis of cinchona alkaloids in beverages

A method for the determination of Cinchona extract (whose main components are the alkaloids cinchonine, cinchonidine, quinidine, and quinine) in beverages by liquid chromatography was developed. A beverage with an alcohol content of more than 10% was loaded onto an OASIS HLB solid-phase extraction cartridge, after it was adjusted to pH 10 with 28% ammonium hydroxide. Other beverages were centrifuged at 4000 rpm for 5 min, and the supernatant was loaded onto the cartridge. The cartridge was washed with water followed by 15% methanol, and the Cinchona alkaloids were eluted with methanol. The Cinchona alkaloids in the eluate were chromatographed on an L-column ODS (4.6 mm id x 150 mm) with methanol and 20 mmol/L potassium dihydrogen phosphate (3 + 7) as the mobile phase. Cinchona alkaloids were monitored with an ultraviolet (UV) detector at 230 nm, and with a fluorescence detector at 405 nm for cinchonine and cinchonidine and 450 nm for quinidine and quinine (excitation at 235 nm). The calibration curves for Cinchona alkaloids with the UV detector showed good linearity in the range of 2-400 microg/mL. The detection limit of each Cinchona alkaloid, taken to be the concentration at which the absorption spectrum could be identified, was 2 microg/mL. The recovery of Cinchona alkaloids added at a level of 100 microg/g to various kinds of beverages was 87.6-96.5%, and the coefficients of variation were less than 3.3%. A number of beverage samples, some labeled to contain bitter substances, were analyzed by the proposed method. Quinine was detected in 2 samples of carbonated beverage.