烯烃不对称双羟化及其反应机理的研究进展

本文综述了近年来四氧化锇催化烯烃不对称双羟化及其反应机理的研究进展。Sharpless等对烯烃双羟化机理的透彻研究导致了不对称双羟化方法的优化。     

金鸡纳碱奎尼丁催化含苯并噻唑基团亚胺与丙二酸酯Mannich反应机理研究

手性催化剂奎尼丁催化丙二酸乙酯与苯并噻唑亚胺的不对称Mannich反应机理研究, 对β-氨基酸酯类衍生物合成具有重要的指导意义. 采用密度泛函理论(DFT)的M06-2X方法, 通过精确计算: (1)确定了奎尼丁催化剂催化活性位点为9位碳上的羟基和位于1位的叔氮原子; (2) S构型反应过渡态能量比R构型反应过渡态能量低, 反应产物以S构型为主; (3)计算进一步表明较低温度有助于提高反应的立体选择性. 计算结果与实验数据相符, 反应获得S构型的β-氨基酸酯类衍生物, 其ee可达到 81%～95%.     

A Sensitive Chemiluminescence Method for Cinchona Alkaloids

Abstract

Chemiluminescence (CL) was achieved by oxidation of sulphide with cerium(IV) in the presence of cinchona alkaloids (quinine, quinidine or cinchonine). The CL intensity was correlated with the concentration of each cinchona alkaloid. Based on this phenomenon, sensitive CL methods for these alkaloids were described. Quinine (4×10^?8～1×10^?4 g/ml), quinidine (1×10^?7 ～ 1×10^?3 g/ml) and cinchonine (1×10^?6 ～ 8×10^?4 g/ml) could be determined with detection limits of 1×10^?8 g/ml, 4×10^?8 g/ml and 6×10^?7 g/ml, respectively.     

Development and validation of RP‐HPLC‐fluorescence method for quantitative determination of quinidine,a probe substrate for P‐glycoprotein inhibition assay using Caco‐2 cell monolayer

A simple, sensitive and specific reverse‐phase high‐performance liquid chromatographic (RP‐HPLC) method with fluorescence detection was developed for quantitation of quinidine from HBSS buffer. The method was applicable in the bi‐directional transport assay for evaluation of the inhibitory effect of test compounds on P‐glycoprotein‐mediated quinidine transport; quinidine was used as a probe P‐glycoprotein substrate. The calibration curve was linear (correlation coefficient ≥99) in the range 0.30–100.00 nm. The method was validated and is specific and sensitive with limit of quantitation of 300 pm for quinidine. The method was found to be accurate and precise in the working calibration range. Stability studies were carried out at different storage conditions where the analyte was found to be stable. The applicability and reliability of the analytical method was evaluated by successful demonstration of efflux ratio (P_appB → A/P_appA → B) in the Caco‐2 cell monolayer efflux assay. The efflux ratio for quinidine (100 nm) alone was 10.8, which reduced to less than 2 in the presence of the classical P‐gp inhibitors verapamil and ketoconazole (100 μm each). Copyright © 2009 John Wiley & Sons, Ltd.     

Chiral recognition by enantioselective liquid chromatography: Mechanisms and modern chiral stationary phases

An overview of the state-of-the-art in LC enantiomer separation is presented. This tutorial review is mainly focused on mechanisms of chiral recognition and enantiomer distinction of popular chiral selectors and corresponding chiral stationary phases including discussions of thermodynamics, additivity principle of binding increments, site-selective thermodynamics, extrathermodynamic approaches, methods employed for the investigation of dominating intermolecular interactions and complex structures such as spectroscopic methods (IR, NMR), X-ray diffraction and computational methods. Modern chiral stationary phases are discussed with particular focus on those that are commercially available and broadly used. It is attempted to provide the reader with vivid images of molecular recognition mechanisms of selected chiral selector–selectand pairs on basis of solid-state X-ray crystal structures and simulated computer models, respectively. Such snapshot images illustrated in this communication unfortunately cannot account for the molecular dynamics of the real world, but are supposed to be helpful for the understanding. The exploding number of papers about applications of various chiral stationary phases in numerous fields of enantiomer separations is not covered systematically.     

Enantiomer separation and indirect chromatographic absolute configuration prediction of chiral pirinixic acid derivatives: Limitations of polysaccharide-type chiral stationary phases in comparison to chiral anion-exchangers

Chiral α-arylthiocarboxylic acids with different substitution patterns, representing new pirinixic acid derivatives with dual PPARα/γ agonistic activities, have been separated into enantiomers on tert-butylcarbamoylquinine and quinidine based chiral anion-exchangers and amylose tris(3,5-dimethylphenylcarbamate) coated silica on analytical and preparative scale. Absolute configurations of individual enantiomers were assigned chromatographically via elution orders on the chiral anion-exchangers and were confirmed by stereoselective syntheses via Ewans auxiliaries that have lead to enantiomeric products with known absolute configurations. The results of both methods were in full agreement. Moreover, the receptor stereoselectivity in PPARα transactivation activities was consistent within the test set of structurally related compounds. Limited correlation (between elution order and substitution) was observed within the set of α-arylthiocarboxylic acids on the amylose tris(3,5-dimethylphenylcarbamate) based chiral stationary phase (CSP), in particular the elution order changed with remote substitution. This clearly demonstrates the risks of chromatographic absolute configuration assignments by prediction from one structural analog to another one, especially with CSPs such as polysaccharide CSPs that are recognized for their broad applicability due to multiple binding and chiral recognition modes. It is therefore of utmost importance that such chromatographic absolute configuration predictions by extrapolation to structural analogs are combined with orthogonal methods for verification of the results.     

A comprehensive chemoselective and enantioselective 2D-HPLC set-up for fast enantiomer analysis of a multicomponent mixture of derivatized amino acids

A feasibility study on the fast enantioselective two-dimensional HPLC separation of racemic amino acid derivatives is presented. The method involves the on-line coupling of a narrow-bore C18 RP column in the first dimension to a short enantioselective column based on nonporous 1.5 μm particles modified with quinidine carbamate as chiral selector in the second dimension. Conceptually, the system was designed to enable both time-controlled repeated transfer of fractions of the eluate and detector-controlled transfer of selected fractions from column 1 to column 2. To avoid volume overloading of the second chiral column, a narrow-bore reversed phase column was installed in the first dimension. Due to the fast (less than 1.5 minutes) enantiomer separation that occurs in the second dimension, the overall analysis time for the two-dimensional separation of a mixture of nine racemic 3,5-dinitrobenzoyl amino acids was optimized at 16 minutes.     

Fluorimetric Flow-Through Sensing of Quinine and Quinidine

We describe a single continuous-flow method for the determination of Quinine (QN) and Quinidine (QD) based on the enhancement of their native fluorescence by on-line transitory retention on a solid support placed in a flow cell. KCl solution was used as carrier/self-eluting solution. The active solid surface is regenerated by the carrier itself which also acts as eluting solution, thus making the microsensing zone reusable for subsequent measurements.In the range of 40 to 1260µL, the response of the sensor (_exc/_em=250/450nm) was directly proportional to the sample volume injected. The sensor was calibrated for three injection volumes: 40, 600 and 1000µL, responding linearly in the range of 40–800, 2–40 and 0.4–20µgL^–1 of QN and 20–600, 5–40 and 0.9–20µgL^–1 of QD with detection limits of 2.2, 0.2 and 0.1µgL^–1 (QN) and 3.9, 0.4 and 0.2µgL^–1 (QD), respectively. The relative standard deviation for ten independent determinations is 1.0% (QN) and 3.9% (QD). The sampling frequency ranges between 40 and 22h^–1 depending on the sample volume injected. This sensor was satisfactorily applied to the determination of QN in soft drink samples and a shampoo, and to the determination of QD in pharmaceutical preparations with equally satisfactory results.     

毛细流自组装成环荧光显微测定血清样品中硫酸奎尼丁

在0.01 mol/L H2SO4的介质中,有聚乙烯醇-124存在时,硫酸奎尼丁(QDS)溶液通过毛细流作用能在憎水性玻璃表面上自组装成环(SOR)。环的最大荧光强度与硫酸奎尼丁的量成正比,据此建立了一种显微荧光自组装成环技术测定血清硫酸奎尼丁的新方法,测定硫酸奎尼丁的线性范围为(0.2~1.4)×10-12mol;检出限(3σ)为2.6×10-14mol。本方法已成功用于血清中硫酸奎尼丁的测定,回收率为93.3%~101.3%。     

Application of cinchona-sulfonate-based chiral zwitterionic ion exchangers for the separation of proline-containing dipeptide rotamers and determination of on-column isomerization parameters from dynamic elution profiles

The interconversion of cis and trans isomers of dipeptides containing C-terminal proline was studied by dynamic chromatography on zwitterionic chiral stationary phases at temperatures ranging from −15 °C to +45 °C The cis–trans isomers could be separated below 0 °C and above 0–10 °C plateau formation and peak coalescence phenomena occurred, which is characteristic for a dynamic process at the time-scale of partitioning. At and above room temperature, full coalescence was observed, which allowed separations of enantiomers without interference from interconversion effects. Analysis of the dynamic elution profiles of the interconverting peptides allowed the determination of isomerization rate constants and thermodynamic activation parameters (isomerization enthalpy, entropy and activation energy). In accordance with established results, isomerization rates and thermodynamic parameters were found to depend on the nature of the N-terminal amino acid. Isomerization barriers were only slightly lower than values determined with other methods but significant differences in the relative contributions of the activation enthalpy and entropy as well as isomerization rates pointed toward selector-moderated isomerization dynamics.