Microwave Irradiation Promoted Synthesis of Aryloxy Acetic Acids

Several aryloxy acetic acids were synthesized under microwave irradiation. The factors, which affect the reaction, were investigated and optimized. It was revealed that the best yields(92.7%—97.4%) were obtained when the molar ratio of the reactants was n(ArOH)∶n(NaOH)∶n(ClCH 2CO 2H) =1∶2.5∶1.2 with microwave irradiation power of 640 W for 65—85 s.

Determination of the enantioselectivity of six chiral aryloxy aminopropanol drugs transport across Caco-2 cell monolayers

This study aimed to determine the transepithelial transport characteristics of chiral drug enantiomers across Caco-2 cell monolayers,a model of human intestinal epithelial membrane.Six chiral aryloxy enantiomers(atenolol,sotalol,celiprolol,carvedilol,metoprolol and propafenone)were tested in bi-directional transport studies.The separation and quantitation of these enantiomers were performed by reversed-phase high-performance liquid chromatography(RP-HPLC)using 2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl isothiocyanate(GITC)as a pre-column derivatizing agent.Bi-directional transport studies demonstrated that celiprolol and carvedilol exhibited significant enantioselectivity in polarized transport at the concentration range tested.The efflux ratio(ER)for(R)-(t)-celiprolol was 8.96,but it was much lower for(S)-(-)-celiprolol which is 3.42 at the concentration of 96.0 mM;carvedilol had the same transport behavior as celiprolol while the difference between the ER values of two enantiomers was not as significant as celiprolol at the concentration of 5.0 mM.They are 2.41 for(R)-(t)-carvedilol and 1.98 for(S)-(-)-carvedilol.But in the transport studies of racemic atenolol,sotalol,metoprolol and propafenone,no enantioselective transport were observed over the concentration range tested.Because P-glycoprotein(P-gp)is highly expressed in Caco-2 cells,we inferred that P-gp might participate in the transport processes of celiprolol and carvedilol in chirally discriminative ways.

STUDIES ON ORGANOMETALLIC COMPOUNDS OF TITANIUM, ZIRCONIUM AND HAFNIUM——SYNTHESIS AND ~1HNMR OF BIS(CYCLOPENTADIENYL)DI(ARYLOXY) METAL DERIVATIVES

<正> In a previous communication we have reported a series of bis(cyclopentadienyl)di(aryl) derivatives of the fourth group of transitional metals. In this paper, the synthesis and ~1HNMR of bis (cyclopentadienyl) di (aryloxy) derivatives of these metals will be given. Due to the increase of metallic properties of transition metals as their perio-

Reversed-phase high-performance liquid chromatographic analysis of seven pairs of chiral drug enantiomers in transport medium after chiral derivatization

A reversed-phase high-performance liquid chromatographic （RP-HPLC） method was established for the determination of the enantiomers of 7 aryloxy aminopropanol drugs （atenolol, sotalol, celiprolol, carvedilol, metoprolol, propranolol and propafenone） in transport medium. The method involved liquid-liquid extraction of chiral drugs from transport medium, and employed 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate （GITC, 1.0 mg/mL in acetonitrile） as a pre-column chiral derivatization reagent. After derivatization, the products were separated on an Agilent Zorbax C8 column （150 min×4.6 mm, 5 μm） at 25 ℃. The mobile phase consisted of a mixture of acetonitrile and 0.01 M phosphate buffer （pH 3.5）. The present methods were specific for the determination of enantiomers of each chiral drug. The absolute recoveries of the enantiomers and internal standards were 〉78%. The relative recoveries of the enantiomers were approximately 100%. The intra- and inter-day variations were 〈 15%. The method was reproducible and sufficiently sensitive to determine the enantiomers of seven aryloxy aminopropanol drugs in transport medium. The method could be used to study the transport of atenolol, sotalol, celiprolol, carvedilol, metoprolol, propranolol and propafenone.

GaI_3 Catalyzed Tetrahydropyranylation of Alcohols and Phenols

In dichloromethane, the nucleophilic addition of alcohols or phenols to 3,4-dihydro-2H-pyran (DHP) was cata-lyzed effectively by gallium triiodide which was generated in situ by the reaction of gallium metal and iodine to give the corresponding tetrahydropyranyl acetals in good to excellent yields.