Asymmetric reduction of ketones with sodium aluminum hydride modified by various chiral diols

New stereoselective reducing reagents were preparedin situ by modification of NaAlH₄ with various chiral diols. The efficiency of 1,4- and 1,3-diols as chiral auxiliaries in the reactions of alkyl aryl ketones with modified NaAlH₄ was considerably higher than that of 1,2-diols. The effect of the nature of the achiral ligand additionally introduced into the chiral hydride reagent on the enantioselectivity of ketone reduction was studied. It was proposed that the sodium cation does not necessarily participate at the stage governing the reaction stereochemistry. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp 459–464, March, 2000.     

毛细管电泳对萘普生对映体的分离及定量分析

以环糊精及其衍生物作为毛细管电泳手性分离的添加剂,采用正极进样,对酸性药物萘普生对映体的分离进行研究,结果表明该途径能在较短的时间内使对映体达到基线分离。还研究了缓冲体系ｐＨ值对萘普生对映体分离的影响,结果表明,ｐＨ５．５时分离效果最佳,且耗时最短。对ＣＥ定量能力（线性,精度）进行了考察,获得满意的结果,线性相关系数为０．９９８,ＲＳＤ低于４．４％。     

高效液相色谱手性流动相添加法拆分奥昔布宁对映体

采用C18固定相,以羟丙基-β-环糊精为手性流动相添加剂,建立了奥昔布宁对映体的高效液相色谱拆分方法。考察了手性添加剂、有机极性调节剂、缓冲盐的种类和浓度以及流动相的pH值和流速及柱温等因素对对映体分离的影响。在最佳分离条件下,奥昔布宁对映体的分离度为1.54,检测限为1.0 ng。该方法简便,重复性好,比手性固定相法更加经济。     

β-环糊精固载硅胶薄层色谱法拆分盐酸克伦特罗对映体

以羧甲基纤维素钠为交联剂,将β-环糊精固载在硅胶GF254表面上,并用其制备薄层色谱板。使用该薄层板拆分了盐酸克伦特罗对映异构体。考察了薄层拆分中展开剂的影响,发现展开剂中醇的种类和比例对拆分效果有较大的影响。分别考察了10种醇与乙腈混合溶剂作展开剂对拆分的影响,结果显示,只有正丁醇-乙腈、仲丁醇-乙腈、叔丁醇-乙腈混合溶剂作展开剂可拆分盐酸克伦特罗对映体。薄层色谱法拆分盐酸克伦特罗对映体的条件为：以1.00 g β-环糊精固载在15.00 g硅胶GF254表面上,并用其制备薄层板,以乙腈-仲丁醇(体积比为20∶80)混合溶剂作展开剂,于室温下展开。在此条件下,盐酸克伦特罗对映体单体在薄层色谱板上的比移值Rf分别为0.34和0.72,分离度Rs为4.09,实现了基线分离,而且样品在薄层色谱板上的斑点大小一致,拆分效果最好。     

Molecular dynamics simulations of the chiral recognition mechanism for a polysaccharide chiral stationary phase in enantiomeric chromatographic separations

We use explicit-solvent fully atomistic molecular dynamics (MD) simulations, permitting all the interactions between the atoms constituting the polymeric chiral stationary phase (CSP), the solvent molecules and the drug molecule enantiomers, to better understand the chiral recognition mechanism that makes chromatographic separation possible. Using amylose tris(3,5-dimethylphenyl carbamate) (ADMPC) as prototype, three solvent systems, and ten racemates as solutes, we seek a molecular dynamics average quantity that could serve as a metric that predicts which of the two enantiomers will elute first and also correlates with the ratio of retention times for enantiomers. To better understand the molecular dynamic chiral recognition that provides the discrimination which results in the separation of enantiomers by high performance liquid chromatography, we examine the differences in hydrogen bonding lifetimes in various donor–acceptor pairs between the drugs and the ADMPC, and map out the differences in ring-ring interactions between the drugs and the ADMPC. Several MD average quantities related to hydrogen-bonding lifetimes correlate with the ratio of retention times for the enantiomers. One of these quantities provides a prediction of the correct elution order 90% of the time, and the ratios of these quantities for the enantiomers provide linear correlation (0.85 coefficient) with experimental separation factors.     

Bioanalysis of drugs and their metabolites by chiral electromigration techniques (2010–2020)

The further development and application of capillary electromigration techniques for the enantioselective determination of drugs and their metabolites in body fluids, tissues, and in vitro preparations during the 2010 to 2020 time period continued to proof their usefulness and attractiveness in bioanalysis. This review discusses the principles and important aspects of capillary electrophoresis- based chiral drug bioassays, provides a survey of the assays reported during the past 10 years and presents an overview of the key achievements encountered in that time period. For systems with charged chiral selectors, special attention is paid on assays that feature field-amplified sample injection to enable the determination of ppb levels of analytes and optimized online incubation procedures for the rapid assessment of a metabolic pathway. Applications discussed encompass the pharmacokinetics of drug enantiomers in vivo and in vitro, the impact of inhibitors on metabolic steps, the elucidation of the stereoselectivity of drug metabolism in vivo and in vitro, and drug enantiomers in toxicological, forensic, and doping analysis.     

Lamellar conglomerates

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Extrapolation of isothermal retention data in gas chromatography for chiral recognition studies

Summary The calculation of capacity factors, k, from net retention times, t_R, and the corresponding dead times, t_M, at different temperatures suffers from the limited accuracy of the t_M values. If the temperature coefficient racy of the t_M values. If the temperature coefficient d ln k/d (1/T) only is required, it is sufficient to determine net retention times (t_R)_p at constant inlet pressure p_i for different temperatures, since the temperature dependence of (t_M)_p can be assumed as (t_M)_p=A·e^B/T, with B being approximately independent of the column inlet pressure and of the nature of the carrier gas. The extrapolation and interpolation of (t_R)_p may be either performed by linear regression or graphically with a nomogram for ln (t_R)_p versus 1/T. The resolution factor, , of two components, e.g. enantiomers which are resolved on a chiral stationary phase, can be treated in a similar way. Examples are given for the resolution of enantiomers of two non-proteinogenic amino acids on the new polysiloxane phase L-Chirasil-CPG.