Assessing chiral self-recognition using chiral stationary phases

Chiral stationary phases were synthesized and their ability to separate racemic precursors from which they were derived was assessed. Taken in conjunction with homochiral recognition previously observed in the solid state, the results of this study reveal that a geometrically controlling π-π interaction has a profound influence on molecular recognition.     

Addition of lactate-derived chiral allyltrichlorostannanes to chiral aldehydes

Chiral lactate-derived allyltrichlorostannanes reacted with chiral α-methyl β-alkoxy and syn and anti α-methyl-β-alkoxy aldehydes to give the corresponding homoallylic alcohols with moderate to high 1,4-syn-diastereoselectivities.     

Diastereomeric recognition of chiral foldamer receptors for chiral glucoses

[reaction: see text] Three chiral aromatic hydrazide foldamers have been designed and synthesized, in which two R- or S-proline units were incorporated at the terminals of their backbones. The 1H NMR, circular dichroism (CD), and fluorescent experiments and molecular dynamics simulations revealed that the foldamers adopted a chiral helical conformation and complexed alkylated glucoses in chloroform with a good diastereomeric selectivity.     

Inherently chiral electrodes: the tool for chiral voltammetry

2,2′-Bis[2-(5,2′-bithienyl)]-3,3′-bithianaphthene oligomers are a model case of electroactive films endowed with “inherent chirality”, originating from a stereogenic element coinciding with the whole electroactive backbone, thus resulting in impressive manifestations. This study highlights their applicative potentialities as low-cost and easy-to-prepare artificial enantiopure electrode surfaces, which display an unprecedented ability to pronouncedly separate voltammetry peaks of enantiomers of quite different chiral probes of applicative interest, concurrently with linear dynamic ranges for peak currents, affording enantiomer excess determination. Thus inherently chiral enantiopure electrodes can indeed be regarded as a key to chiral voltammetry.     

Advanced dress-up chiral columns: New removable chiral stationary phases for enantioseparation of chiral carboxylic acids

This paper describes the preparation of new dress-up columns featuring reproducibly removable and replaceable chiral stationary phases. After synthesizing perfluroalkylated quinine and quinidine derivatives as chiral stationary phase compounds (F-CSPs), we adsorbed them reversibly onto a fluorous LC column through pumping of their solutions. Using this dress-up chiral column and fluorophobic elution of aqueous ammonium formate/MeOH mixtures, we could enantioseparate four racemic N-acetyl amino acids, dichlorprop, and sixteen fluorescent 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC)-derivatized amino acids. Dressing and undressing of the coated F-CSPs could be controlled by varying the fluorophilicity and fluorophobicity of the eluent. The relative standard deviations of the retention times, the retention factors, the number of theoretical plates, the enantioseparation factors, and the resolutions of each of four preparations of such dress-up columns were all less than or equal to 5.26% (from 20 repeated analyses); the reproducibilities from four different preparations were all less than or equal to 10.6%. These columns also facilitated highly sensitive and selective analyses of AQC-amino acids when detected using LC–MS/MS.     

双手性选择单元手性固定相的研究进展

手性固定相（chiral stationary phase,CSP）作为手性色谱分离的核心技术,在手性化合物的识别和分离中得到广泛应用。以双手性选择单元结合作为CSP是近些年的研究热点,研究表明,两种手性选择单元相结合的CSP可增加手性识别位点,显著提高分离效果。本文介绍了近几年双手性选择单元手性固定相在手性分离中的研究进展,并对其发展前景进行了展望。     

One-pot synthesis of chiral azetidines from chloroaldehyde and chiral amines

A variety of chiral azetidinepiperidines have been synthesized utilizing an expedient one-pot union of piperidine chloroaldehyde with chiral amines. This two step one-pot procedure provides access to an interesting set of compounds that retain the chiral purity of the starting chiral amine.     

Comparative studies of various run buffers for chiral capillary electrophoresis using chiral crown ether as a chiral selector

In the capillary electrophoretic separation of primary amine enantiomers using (+)-(18-crown-6)-tetracarboxylic acid (18C6H4) as a chiral selector, the presence of run buffer constituents such as tris(hydroxymethyl)aminomethane (Tris) or Na+ competing with analytes for 18C6H4, diminishes the effectiveness of 18C6H4. In order to determine appropriate buffer systems for 18C6H4, various run buffer cationic components including Tris, 1,3-bis[tris(hydroxymethyl)methylamino]propane, bis(2-hydroxyethyl)iminotris(hydroxymethyl)methane, triethanolamine, tetramethylammonium, and Na+ were compared. Quantitative studies of the effects of the competitive constituents were carried out by measuring the electrophoretic mobilities of histidine as a function of the 18C6H4 concentration. We also derived a simple equation to estimate the optimal chiral selector concentration for a maximum mobility difference in the presence of a competitive inhibitor.     

A chiral furocoumarin

The furocoumarin 1,2‐di­hydro‐2‐(1,2‐di­hydroxy­prop‐2‐yl)‐8H‐furo­[2,3‐h]­benzo­pyran‐8‐one crystallizes from methanol–water as the monohydrate C₁₄H₁₄O₅·H₂O. Both chiral centers have the S configuration. Both OH groups and both H atoms of the water mol­ecule form intermolecular hydrogen bonds with O?O distances in the range 2.7686 (18)–2.8717 (18) Å.     

Deepened chiral cavitands

Deep cavitands bearing eight asymmetric centers on their upper rims are prepared from octamino resorcinarenes. The resorcinarenes are acylated with Fmoc d- and l-alanine or Fmoc glycine acid chlorides. The asymmetric centers create a chiral magnetic environment as shown by binding achiral ?-caprolactam. The chiral steric environment shows modest enantioselectivity (55% de) for chiral guests such as pinane diols bound inside the cavitand.     

Inherently chiral calixarenes

Due to the nonplanarity of the basic 1 _n -metacyclophane system, calixarenes and resorcarenes can be transformed into molecules with inherent chirality. Various attempts to achieve this goal are reviewed. Special emphasis is given to derivatives withC _n -symmetry, including derivatives of spherand calixarenes and other calixarene-like macrocycles.This paper is dedicated to the commemorative issue on the 50th anniversary of calixarenes.     

Reagent controlled addition of chiral sulfur ylides to chiral aldehydes

The degree of reagent and substrate control in the reaction of chiral sulfur ylides with chiral aldehydes has been investigated. Specifically, the reactions of the two enantiomers of the chiral benzyl sulfonium salt 1 with glyceraldehyde acetonide were studied in detail. Of the two new stereogenic centers created, it was found that the C1 stereochemistry was largely controlled by the reagent, whereas control at the C2 center was dependent on the aldehyde used. In one case, the trans isomer was produced via reversible formation of the intermediate betaine, whereas in the alternative case, the C2 center was under Felkin Anh/Cornforth control through non-reversible formation of the betaine. Thus, the aldehyde stereocenter influenced the degree of reversibility in betaine formation, which impacted on the stereocontrol at the C2 position.     

非均匀取代淀粉衍生物手性固定相的制备及其手性识别能力

通过区域选择性方法制备了两种新型淀粉衍生物,分别为淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)和淀粉2-苯甲酸酯-3-(3,5-二氯苯基氨基甲酸酯)-6-(4-甲基苯基氨基甲酸酯),将二者分别涂覆于氨丙基硅胶后用作液相色谱手性固定相。研究表明:所制备的手性固定相显示出特异的手性识别能力,其手性识别能力明显高于均匀取代淀粉衍生物——淀粉三(3,5-二氯苯基氨基甲酸酯),取代基的性质及在葡萄糖单元上的位置对手性固定相的手性识别能力有较大的影响。一些未在商品化的手性柱Chiralpak AD上得到有效分离的手性化合物在所制备的固定相上得到了更好的分离。所测试的8对对映体在淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)固定相上均得到了分离,因而此固定相的手性识别能力较强,具有潜在的应用价值。     

Enantioselective resolution of chiral aromatic acids by biphasic recognition chiral extraction

This paper reports a new chiral separation technology—biphasic recognition chiral extraction for the separation of aromatic acid enantiomers such as α-cyclohexyl-mandelic acid (CHMA) and naproxen (NAP). The biphasic recognition chiral extraction system was established by adding hydrophobic d(l)-isobutyl tartrate in 1,2-dichloroethane organic phase and hydrophilic β-cyclodextrin (β-CD) derivative in aqueous phase, which preferentially recognize the (R)-enantiomer and (S)-enantiomer, respectively. These studies involve an enantioselective extraction in a biphasic system, where aromatic acid enantiomers form complexes with the β-cyclodextrin derivative in the aqueous phase and d(l)-isobutyl tartrate in the organic phase, respectively. Factors affecting the extraction mechanism are analyzed, namely the influence of the concentrations of the extractants and aromatic acid enantiomers, the types of the extractants, pH, and temperature. The experimental results show that the biphasic recognition chiral extraction is of much stronger chiral separation ability than the monophasic recognition chiral extraction, which utilizes the cooperations of the forces of the tartrate and the β-CD derivative. Hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (ME-β-CD) have stronger recognition abilities for the (S)-aromatic acid enantiomers than those for (R)-aromatic acid enantiomers, among which HP-β-CD has the strongest ability. d-Isobutyl tartrate preferentially recognizes (R)-CHMA and (S)-NAP, while l-isobutyl tartrate preferentially recognizes (S)-CHMA and (R)-NAP. The maximum enantioselectivities of CHMA and NAP are 2.49 and 1.65, under conditions at which the pH values of the aqueous phases are 2.7 and 2.5, at the ratio of 2:1 of [isobutyl tartrate] to [HP-β-CD].     

Resorcinarene-based cavitands with chiral amino acid substituents for chiral amine recognition

Resorcinarene-based deep cavitands alanine methyl resorcinarene acid (), alanine undecyl resorcinarene acid () and glycine undecyl resorcinarene acid (), which contain chiral amino acids, have been synthesized. The upper rim of the resorcinarene host is elongated with four identical substituents topped with alanine and glycine groups. The structures of the new resorcinarenes were elucidated by nuclear magnetic resonance (NMR), mass spectrometry (MS) and the sustained off-resonance irradiation collision induced dissociation (SORI-CID) technique in FTICR-MS. These studies revealed that eight water molecules associate to the cavitand, two for each alanine group. The alanine substituent groups are proposed to form a kite-like structure around the resorcinarene scaffold. The binding of , , and with chiral R- and S-methyl benzyl amines was studied by (1)H NMR titration, and compared to that of a binary l-tartaric acid and the monoacid phthalyl alanine (). The results show that these compounds interact with amine guests; however, with four carboxylic acid groups, they bind several amine molecules strongly while the binary l-tartaric acid only binds one amine guest strongly. The simple compound , which contains one carboxylic group, shows weak binding to the amines. The (1)H NMR titration of with primary, secondary, and tertiary chiral amines showed that it can discriminate between these three types of amines and showed chiral discrimination for chiral secondary amines.     

Amphiphilic Schiff base organogels: metal-ion-mediated chiral twists and chiral recognition

New amphiphilic gelators that contained both Schiff base and L-glutamide moieties, abbreviated as o-SLG and p-SLG, were synthesized and their self-assembly in various organic solvents in the absence and presence of metal ions was investigated. Gelation test revealed that o-SLG formed a thermotropic gel in many organic solvents, whilst p-SLG did not. When metal ions, such as Cu(2+), Zn(2+), Mg(2+), Ni(2+), were added, different behaviors were observed. The addition of Cu(2+) induced p-SLG to from an organogel. In the case of o-SLG, the addition of Cu(2+) and Mg(2+) ions maintained the gelating ability of the compound, whilst Zn(2+) and Ni(2+) ions destroyed the gel. In addition, the introduction of Cu(2+) ions caused the nanofiber gel to perform a chiral twist, whilst the Mg(2+) ions enhanced the fluorescence of the gel. More interestingly, the Mg(2+)-ion-mediated organogel showed differences in the fluorescence quenching by D- and L-tartaric acid, thus showing a chiral recognition ability.     

A concise, modular synthesis of chiral peraza-macrocycles using chiral aziridines

[reaction: see text] Novel chiral peraza-macrocycles were synthesized from chiral aziridines as a common building block. Efficient syntheses of chiral [26]-N(6), [12]-N(4), [9]-N(3), and [14]-N(4) systems were accomplished.