Crystal structures of heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin complexes with (R)- and (S)-Flurbiprofen

Hepatakis(2,3,6-tri-O-methyl)--cyclodextrin (TM--CDx) forms crystalline complexes with (R)-Flubiprofen (R-FP), C₆₃H₁₁₂O₃₅C₁₅H₁₃O₂F·H₂O, and (S)-Flurbiprofen (S-FP), C₆₃H₁₁₂O₃₅C₁₅H₁₃O₂F. The crystal structures were determined by X-ray analysis. Crystals of both compounds are orthorhombic and the space group isP2₁2₁2₁ with cell dimensions:a=15.092(2),b=21.714(3), andc=28.269(4) Å for theR-FP complex, anda=15.271(2),b=21.451(3) andc=27.895(3) Å for theS-FP complex. The macrocyclic ring of TM--CDx is markedly distorted because of the inability to form intramolecular hydrogen bonds and the steric hindrance involving methyl groups. In both complexes, the phenyl group is inserted into the host cavity from the O(2), O(3) side, which is wider than the O(6) side. The biphenyl moiety ofR-FP is fixed in theR-configuration within the host cavity. The phenyl group ofS-FP is disordered, andR-andS-configurations are statistically distributed with equal probability. TM--CDx molecules are stacked along theb axis to form a column structure. The TM--CDx molecule is laterally shifted with respect to the column axis, and a half of the guest molecule protrudes outside from the crevis of the column. The carboxyl group ofR-FP forms a hydrogen bond with water located outside the host cavity, while the carboxyl group ofS-FP is hydrogen-bonded to an oxygen atom of an adjacent TM--CDx. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82064 (24 pages).     

萘普生及其衍生物的手性固定相法直接拆分机理

用不同的酰氯化合物与萘普生反应,制备了一系列萘普生衍生物。在正相色谱条件下,对萘普生及其衍生物系列在(R,R)-Whelk-O 1手性固定相(chiral stationary phase,CSP)上进行了对映体拆分研究。实验考察了流动相组成、分离温度等因素对手性分离的影响,并根据相应热力学参数对萘普生及其衍生物在该手性固定相上的手性识别机理进行了初步探讨。研究结果表明:萘普生及其衍生物在Whelk-O 1 CSP上的对映体分离有着与一般正相色谱明显不同的特征,其分离因子α值与流动相组成关系曲线出现了峰值,且分离因子极大值所对应的流动相组成分别为极性较大的20%(V/V,下同)异丙醇/正己烷混合溶剂体系和40%异丙醇/正己烷混合溶剂体系。     

Chiral bis(mandelato)borate salts for resolution via metathesis crystallization

Spiroborate anions have potential for crystallization or resolution and chiral bis(mandelato)borate anions can be used for the efficient resolution of a diverse range of racemic cations via diastereomeric salt formation. The syntheses, X‐ray crystal structures and solubilities of three chiral bis(mandelato)borate salts, namely poly[[aqua‐μ₃‐bis[(R )‐mandelato]borato‐lithium(I)] monohydrate], [Li(C₁₆H₁₂BO₆)(H₂O)]_n or Li[B(R‐Man)₂]·H₂O, (1), ammonium bis[(R )‐mandelato]borate, NH₄⁺·C₁₆H₁₂BO₆⁻ or NH₄[B(R‐Man)₂], (2), and tetra‐n‐butylammonium bis[(R )‐mandelato]borate, C₁₆H₃₆N⁺·C₁₆H₁₂BO₆⁻ or NBu₄[B(R‐Man)₂], (3), are reported. They all have a B_S configuration and show a reasonably well‐conserved anion geometry. The main conformational variation is the orientation of the two phenyl groups, supporting the idea that [B(Man)₂]⁻ is a semi‐rigid anion. The salts are differentially soluble in a range of solvents, meaning they could be useful as reagents for resolution via a metathesis crystallization approach.     

Inclusion of water by a crown amide. First crystal structure of a respective host-guest combination

Crown amide (1) forms a stoicheiometric 1:1 inclusion complex with water, the X-ray crystal structure of which is reported. Crystals of1 · H₂O are triclinic, space groupP1, witha=7.503(1),b=11.394(3),c=13.443(2) Å, =107.066(18), =96.627(10), =106.377(14)°, andZ=2.R _F =0.039 for 1697 MoK reflections [I>3(I)] measured at 24°C. The structure features a hydrogen bonded hostguest relationship with concrete1 · H₂O units. Hydrogen bonds are between the water oxygen and O(4), N(4), respectively. The crystal packing shows a cavity arrangement of four ligands around each water molecule. Supplementary Data relating to this article are deposited with the British Library as Supplementary Publication No. SUP 82055 (16 pages).     

β—环糊精对D／L—酪氨酸对映体的手性识别及超分子包合物的合成

利用圆二色谱研究了β－环糊精（β－ＣＤ）对Ｄ／Ｌ酪氨酸的手性识别行为，制备出了β－ＣＤ与Ｌ－酪氨酸（Ｌ－Ｔｙｒ）的固体超分子化合物，并用元素分析、薄层分析、Ｘ射线粉末衍射及热分析对包合物进行了表征，用荧光光谱法测定了包合物的形成常数．实验结果表明，β－ＣＤ具有选择包结Ｌ－酪氨酸的特性；主客体形成１１的包合物，其组成为Ｌ－Ｔｙｒ／β－ＣＤ·１２Ｈ２Ｏ；稳定常数为５．１３×１０３Ｌ／ｍｏｌ；包合物的热稳定性比主客体皆有改善     

环糊精对甲基麻黄碱手性识别的电喷雾质谱研究

利用质谱仪,使用电喷雾离子源,分别研究了以α-环糊精、β-环糊精和产环糊精作为手性拆分剂对手性药物甲基麻黄碱的手性识别效应．实验结果表明,3种环糊精对甲基麻黄碱对映体均有较强的手性识别效应,Rchiral分别为2．43、3．51、4．52．研究了电压的变化对α-环糊精、β-环糊精和γ-环糊精的手性识别的影响,研究发现,在不同的电压下,这3种环糊精对甲基麻黄碱均有手性识别能力．     

Crystallographic and DFT studies on host-guest complexes consisting of zinc bisporphyrinates and 1-phenylethylamine

We have investigated the chirality transfer from 1-phenylethylamine to a 5-amino-1,3-phthalic acid diamide-linked zinc bisporphyrinate through crystallographic and DFT studies. When the hosts were mixed with optically pure 1-phenylethylamine, CD showed moderate signals in the Soret band region. Single crystals of the corresponding 1:1 and 1:2 host-guest complexes were obtained. We present the first crystallographic structure of a 1:2 host-guest complex consisting of a bisporphyrin host and chiral monoamine guests. The structure reveals that the host-guest interactions are different for two guest molecules. The first guest is involved in a hydrogen bond and π-π interactions, while the second one is only involved in π-π interactions, which has not been observed in previous studies. The corresponding chirality transfer mechanism was also rationalized by DFT calculations.

     

Molecular Dynamic Study for Chiral Discrimination of a -Phenylethylamine by Modified Cyclodextrin in Gas Chromatography

A molecular dynamic method in conjunction with a statistic test has been utilized to model chiral recognition of a -phenylethylamine on heptakis (2,6-di-O-butyl-3-O-butyryl)-b -cyclodextrin in gas chromatography. The modelling data correlated with the chromatographic elution order, and indicated that the preferred site of a -phenylethylamine is the interior of cavity.     

Enantiomeric Recognition of d- and l-Amino Acid Methyl Ester Hydrochlorides by New Chiral Bis-pyridino-18-crown-6 Substituted with Urea, and Diphenyl Groups

The article reports the synthesis and chiral recognition properties of a new chiral bis-pyridino-18-crown-6 (7), having urea, diphenyl, and allyloxy groups. The chiral bis-pyridino-18-crown-6 was prepared by a thirteen-steps procedure from the commercially available (S)-(+)-mandelic acid and chelidamic acid. The association constants (K _a) (1.33 × 10³–3.20 × 10³) for enantiomeric recognition of d- and l-amino acid methyl ester hydrochlorides using the chiral bis-pyridino-18-crown-6 have been examined by ¹H-NMR titration method in CDCl₃ at 25 °C. The chiral bis-pyridino-18-crown-6 showed higher association constants for the d-series amino acid methyl ester (d-AlaOMe, d-LeuOMe, d-MetOMe) hydrochlorides as compared to the corresponding l-series (l-AlaOMe, l-LeuOMe, l-MetOMe) hydrochlorides.     

Crystal structure of supramolecular complexes formed by 18-crown-6 andcis-anti-cis-dicyclohexano-18-crown-6 (host) with 3,4-diaminofurazane (guest)

An X-ray—diffraction study is reported for two molecular complexes containing 3,4-diamino-1,2,5-oxadiazole as guest (G) with 18-crown-6 (18-C-6) andcis-anti-cis-dicyclohexano-18-crown-6 (DCH-6B) as host. Both complexes are of the polymeric-chain structure with the guest molecule bridging two crown neighbours. ComplexI: [18-C-6*G*H₂O], 111, monoclinic,P2₁/n,a=8.171(1),b=15.042(2),c=16.209(6) Å, =101.15(2)°, finalR-factor 0.068. ComplexII: [DCH-6B*G], 11, monoclinicC2/c,a=21.212(4),b=9.380(2),c=13.049(3) Å, =108.61(3)°, finalR 0.047.     

Enantioseparation of 3-Hydroxycarboxylic Acids via Diastereomeric Salt Formation by 2-Amino-1,2-diphenylethanol (ADPE) and Cinchonidine

Enantioseparation of 3-hydroxycarboxylic acids via diastereomeric salt formation was demonstrated using 2-amino-1,2-diphenylethanol (ADPE) and cinchonidine as the resolving agents. Racemic 3-hydroxy-4-phenylbutanoic acid (rac-1), 3-hydroxy-4-(4-chlorophenyl)butanoic acid (rac-2), and 3-hydroxy-5-phenylpentanoic acid (rac-3) were efficiently resolved using these resolving agents. Moreover, the successive crystallization of the less-soluble diastereomeric salt of 1 and cinchonidine using EtOH yielded pure (R)-1 · cinchonidine salt in a high yield. The crystal structures of less-soluble diastereomeric salts were elucidated and it was revealed that hydrogen bonding and CH/π interactions play an important role in reinforcing the structure of the less-soluble diastereomeric salts.     

环糊精对手性药物伪麻黄碱分子识别的电喷雾飞行时间质谱研究

用电喷雾正交飞行时间质谱仪分别研究了以α－环糊精、β－环糊精和γ－环 糊精作为手性拆分剂对手性药物伪麻黄碱的分子识别效应,同时还分别研究了 Nozzle电的变化对α－环糊精和γ－环糊精的手性识别的影响。在质谱图中能明显 反映出三种手性拆分剂都具备很强的手性识别能力,随Nozzle电压的改变,三种手 性拆分剂双分别具有各自的手性识别特征。     

高效液相色谱手性固定相法拆分四面体金属簇合物

在正相条件下,在Ch iralpak(AD-H和Ch iralcel(OD-H两种手性色谱柱上,首次直接拆分了三种外消旋过渡金属簇合物,考察了流动相中极性添加剂醇对手性拆分的影响.结果发现,氢键作用在手性识别过程中起重要作用,而且不同的色谱柱填料有不同的选择性.     

高效液相色谱手性固定相法分离取代环己酮及取代环己醇的对映体

在4种自制的涂敷型纤维素衍生物手性柱，即纤维素三苯甲酸酯(CTB)、纤维素三(4-甲基苯甲酸酯)(CTMB)、纤维素三苯基氨基甲酸酯(CTPC)和纤维素三(3，5-二甲基苯基氨基甲酸酯)(CDMPC)与小分子的Prikle型(S，S)-Whelk—O1手性柱上对取代环己酮及取代环己醇进行了对映体分离。研究了溶质的立体结构因素对手性分离的影响，并初步探讨、比较了溶质在这两种手性柱上的手性识别的机理。结果发现，在(S，S)-Whelk—O1柱上溶质与固定相之间的吸引作用是手性识别的主要原因，而对于纤维素衍生物手性柱，溶质的空间结构在手性空腔中的空间适应性可能是手性识别的关键。     

Enantioselective Recognition of Racemic Amino Alcohols in Aqueous Solution by Chiral Metal-Oxide Keplerate {Mo132} Cluster Capsules

Determining the relative configuration or enantiomeric excess of a substance may be achieved using NMR spectroscopy by employing chiral shift reagents (CSRs). Such reagents interact noncovalently with the chiral solute, resulting in each chiral form experiencing different magnetic anisotropy; this is then reflected in their NMR spectra. The Keplerate polyoxometalate (POM) is a molybdenum-based, water-soluble, discrete inorganic structure with a pore-accessible inner cavity, decorated by differentiable ligands. Through ligand exchange from the self-assembled nanostructure, a set of chiral Keplerate host molecules has been synthesised. By exploiting the interactions of analyte molecules at the surface pores, the relative configuration of chiral amino alcohol guests (phenylalaninol and 2-amino-1-phenylethanol) in aqueous solvent was establish and their enantiomeric excess was determined by ¹H NMR using shifts of ΔΔδ=0.06 ppm. The use of POMs as chiral shift reagents represents an application of a class that is yet to be well established and opens avenues into aqueous host-guest chemistry with self-assembled recognition agents.     

麦芽糖作选择剂西酞普兰手性毛细管电泳分析及拆分机理研究

研究了以麦芽糖为选择剂的毛细管电泳手性拆分方法。以抗抑郁药物西酞普兰对映体的分离和定量测定为实例,考察了分离条件,在40%(m/m)麦芽糖、8.0×10-2mol/L磷酸盐运行缓冲液(pH5.0)中,分离电压20kV时,西酞普兰对映体分离度达2.3。测定S-( )-西酞普兰中R-(-)异构体的含量,在0.05~4.00g/L浓度范围内线性关系良好。R-(-)-西酞普兰与S-( )-西酞普兰的检出限分别为0.0453g/L和0·0473g/L,线性相关系数均>0.9978。以荧光光谱法对西酞普兰与麦芽糖的相互作用进行了考察,并较系统地对拆分机理进行了研究。证明麦芽糖的手性识别能力与其浓度有关,当麦芽糖达到一定浓度后将形成聚集体,而麦芽糖的拆分作用就主要体现在其聚集体疏水空腔的立体作用上。     

Enantioseparation of Novel Chiral Tetrahedral Clusters on a Chiral Stationary Phase (CSP) by High Performance Liquid Chromatography

In recent years, the synthesis of chiral tetrahedral clusters has been studied extensively and various types are accessible , which are a kind of organometallic compounds with greatly growing interest due to their potential application to asymmetric reaction catalysts. As an efficient     

Structure and Molecular Recognition of Chiral Amino-Cyclodextrin: One-dimensional Array by Self-assembly in Solid and Chiral Discrimination in Solution

Abstract

The crystal structure and molecular recognition behaviour of a new chiral-amino cyclodextrin are reported; van der Waals interaction, hydrogen bond and the electrostatic interactions play an important role in the self-assembling process and chiral recognition for (R)-(-)-and (S)-(+)-mandelic acid.     

Comparative studies of immobilized polysaccharide derivatives chiral stationary phases for enantioseparation of furanocoumarins and dihydroflavones and discussion on chiral recognition mechanism

Enantiomeric separation of furanocoumarins and dihydroflavones compounds were systematically studied in the normal-phase mode using four different polysaccharide-type chiral stationary phases, namely, Chiralpak IA, Chiralpak IC, Chiralpak IG, and Chiralpak IK-3 by high-performance liquid chromatography. The effect of alcohol modifiers and alcohol content on enantiomeric separation was evaluated for the separation of furanocoumarins and dihydroflavones. All the eight compounds have achieved baseline separation with the resolutions ranging between 1.52 and 23.11. For a better insight into the enantiorecognition mechanisms, thermodynamic analysis was carried out. The mechanisms of chiral recognition have been discussed. Among four chiral columns, Chiralpak IG exhibited the most universal and the best enantioseparation ability toward furanocoumarins and dihydroflavones when used n-hexane-isopropanol and n-hexane-ethanol as mobile phase, respectively. The steric hindrance, hydrogen bonding, and π-π interaction played major roles in chiral recognition on Chiralpak IG. By comparing four chiral columns, this work systematically analyzed the separation methods of furanocoumarins and dihydroflavones for the first time and reported some active chiral ingredients of traditional Chinese medicine that have never been separated, which provided a further insight into the enantioseparation of furanocoumarins and dihydroflavones on chiral stationary phases.     

手性分子识别的质谱研究进展

由于质谱分析速度快以及所需样品量少等特点，使得质谱手性识别技术在现代分析化学、有机化学甚至生物化学等领域得到青睐，阐述了手性分子识别的质谱研究最新动向，对其原理和所使用的手性选择剂作了介绍。