Comparison of monomeric and polymeric amino acid based surfactants for chiral separations

To better understand chiral recognition with polymeric amino acid based surfactants, the chromatographic performance of 18 monomeric and polymeric surfactants were compared for chiral analytes with various charge states and hydrophobicities. In this study, four amino acids (glycine, L-alanine, L-valine, and L-leucine) were chosen, and all possible combinations of the chiral single amino acid and dipeptide surfactants were synthesized. The results indicate that polymeric surfactants usually provide better chiral resolution for enantiomers of lorazepam, temazepam, 1,1'-bi-2-naphthol, and propranolol as compared to monomeric surfactants. In contrast, monomers perform better for chiral recognition of the 1,1'-bi-2-naphthyl-2,2'-diyl hydrogenphosphate enantiomers.     

Efficient resolution of racemic 1,1'-bi-2-naphthol with chiral selectors identified from a small library

Efficient resolution of racemic 1,1'-bi-2-naphthol, a well-studied analyte in chiral separation, was achieved using selectors developed from a small library. Separation factors (up to 7.2) obtained are significantly higher than the ones reported previously for this analyte. The library consists of 121 members and it does not contain the pi deficient 3,5-dinitrobenzoyl (Dnb) group. These highly efficient stationary phases may lead to the practical large-scale chromatographic resolution of enantiomers of 1,1'-bi-2-naphthol, which are widely used as chiral auxiliaries and ligands in asymmetric synthesis.     

Comparative study on the enantiomer separation of 1,1'-binaphthyl-2,2'diyl hydrogenphosphate and 1,1'-bi-2-naphthol by liquid chromatography and capillary electrophoresis using single and combined chiral selector systems

The chiral recognition ability of single and dual selectors, that were used as additives, have been investigated by HPLC and CE. Native beta- and gamma-cyclodextrins, permethylated beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, cholic acid and taurodeoxycholic acid sodium salts were applied as chiral selectors, whereas the atropisomers of 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate, and 1,1'-bi-2-naphthol served as model compounds. It was found that all investigated selectors, except for gamma-cyclodextrin, display the same affinity pattern for binaphthyl enantiomers, i.e., binding the S more strongly than the R enantiomer. However, the differences in the phase distribution of chiral selectors led to the opposit elution order of enantiomers: with cyclodextrins, the first eluted is S enantiomer, while R is the first eluted for bile salts. Under the conditions studied, cyclodextrins (except gamma-cyclodextrin), as well as cholic acid sodium salts acting singly, enable the separation of 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate enantiomers both by HPLC and CE methods, while 1,1'-bi-2-naphthol enantiomers were resolved only under CE conditions with permethylated cyclodextrin or bile salts. In both techniques the application of dual systems could improve resolution or make it worse (oreven cancel), depending on the sign of enantioselectivity of particular selectors, their concentrations and localization: mobile or stationary phase. It has been found that the mechanism of separation as well as interactions occurring between two selectors may be followed by using combined HPLC and CE methods. The obtained results proved that, as well as beta-CD, TM-beta-D and gamma-CD also form inclusion complexes with cholic acid sodium salts. The reversal of elution order may be realized by two procedures: changing a single selector, i.e., cyclodextrin on cholic acid sodium salt or vice versa, and by changing the proportion of selectors in the combined bile salt-cyclodextrin system.     

手性联萘酚配合物催化的缺电子烯烃不对称环氧化反应

缺电子烯烃的不对称环氧化反应是有机合成领域最具有挑战性的课题之一。手性联萘酚配体所修饰的催化剂是一种很优异的C2轴对称手性诱导源,可以催化各种α,β－不饱和羰基化合物如α,β－不饱和酮、α,β－不饱和羧酸脂等的不对称环氧化反应,具有良好的催化活性和对映选择性。本文对由手性联萘酚类配体所修饰的小分子催化剂、聚合物负载的催化剂和自负载催化剂在不饱和羰基化合物的催化不对称环氧化反应中的应用进行了综述,探讨了催化剂结构、配位金属原子、添加物、氧化剂、溶剂和反应温度等因素对手性联萘酚催化剂催化效能和对映选择性的影响。     

New methods of resolution and purification of racemic and diastereomeric amino alcohol derivatives using boric acid and chiral 1,1'-bi-2-naphthol

Resolution of the racemic amino alcohol derivatives 1-6 is readily achieved to obtain enantiomerically enriched compounds using chiral 1,1'-bi-2-naphthol and boric acid in solvents such as CH(3)CN, THF, and MeOH. Purification of the diastereomeric mixture 7 has also been carried out following this method. The corresponding intermediate ammonium borate complexes were also characterized by X-ray diffraction methods.     

A chiral porous metal-organic framework for highly sensitive and enantioselective fluorescence sensing of amino alcohols

A highly porous and fluorescent metal-organic framework (MOF), 1, was built from a chiral tetracarboxylate bridging ligand derived from 1,1'-bi-2-naphthol (BINOL) and a cadmium carboxylate infinite-chain secondary building unit. The fluorescence of 1 can be effectively quenched by amino alcohols via H-bonding with the binaphthol moieties decorating the MOF, leading to a remarkable chiral sensor for amino alcohols with greatly enhanced sensitivity and enantioselectivity over BINOL-based homogeneous systems. The higher detection sensitivity of 1 is due to a preconcentration effect by which the analytes are absorbed and concentrated inside the MOF channels, whereas the higher enantioselectivity of 1 is believed to result from enhanced chiral discrimination owing to the cavity confinement effect and the conformational rigidity of the BINOL groups in the framework. 1 was quenched by four chiral amino alcohols with unprecedentedly high Stern-Volmer constants of 490-31200 M(-1) and enantioselectivity ratios of 1.17-3.12.     

A giant vesicle forming single tailed chiral surfactant for enantioseparation by micellar electrokinetic chromatography

Light microscopy has shown the existence of giant bilayer vesicles in aqueous solutions of a novel chiral surfactant, sodium N-[4-dodecyloxybenzoyl]-L-valinate, which acts as a very good chiral selector for enantioseparation of (+/-)-1,1'-bi-2-naphthol and (+/-)-1,1'-binaphthyl-2,2'-diylhydrogenphosphate by micellar electrokinetic chromatography.     

Evaluation of the enantiomeric resolution of 7,8-dihydroxy-7,8-dihydrobenzo[a]-pyrene and its 6-fluoro and 6-bromo derivatives on polysaccharide-derived stationary phases

The enantiomeric resolution and the elution order of (+/-)-trans-7,8-dihydrodiols of benzo[a]pyrene and its 6-fluoro and 6-bromo derivatives were analyzed on three polysaccharide-based columns: Daicel Chiralcel CA-I (cellulose triacetate), OF, and OG [cellulose tris(4-chloro- and 4-methylphenylcarbamate)]. For comparison, the separation of (+/-)-1,1'-bi-2-naphthol was evaluated on the OG and OF columns. Possibly similar interactions of (S)-1,1'-bi-2-naphthol and (7S,8S)-isomers of 6-halo-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene with the chiral sorbent are suggested.     

Enantioselective fluorescent recognition of mandelic acid by unsymmetrical salalen and salan sensors

As sensors with multiple chiral centers, salalen 1 and salan 2 composed of trans-cyclohexane-1,2-diamine (trans-DACH) and 1,1'-bi-2-naphthol (BINOL) units were designed and synthesized. Fluorescent recognition studies of resulting sensors towards mandelic acid (MA) reveal that salan 2a containing (R)-BINOL and (R,R)-DACH exhibits highly sensitive and enantioselective response towards MA. The relationship between the chirality combination and the enantioselectivity is discussed. Based on the studies of concentration and solvent effect on the recognition process of 2a, it was found that the sensitivity and enantioselectivity could be enhanced via changing the concentration of sensors or altering the polarity of solvents. To explain why higher enantioselectivity can be achieved in moderate polar solvent other than in nonpolar or polar solvent, a solvent-guest competition mechanism, which may shed a light on the enhancement of the enantioselectivity of chiral recognition and noncovalent asymmetric catalysis, has been proposed and validated.     

pH-dependent cyclodextrin capillary electrophoresis resolution of atropisomers

Five noncommercial and four commercially available cyclodextrin (CD) derivatives were tested as chiral auxiliaries for the capillary electrophoretic (CE) resolution of racemic 1,1'-bi-(2-naphthol) (BN), 1,1'-binaphthyl-2,2'-diyl hydrogenphosphate (BNHP), and 1,1'-binaphthyl-2,2'-diamine (BNA) at pH 4.0, 6.5, and 8.6. The noncommercial CDs were ethyloxycarbonyl-gamma-CD (ethylcarbonate-gamma-CD), dimethylamino ethyloxycarbonyl-beta-CD, a mercaptosuccinic acid derivative of beta-CD, a maleic acid derivative of beta-CD and heptakis(6-deoxy-6-amino)-beta-CD derivative with one amino group on the C-6 carbon of each glucose unit. Except for the latter, the remaining derivatives were synthesized for this work. Also commercially available methyl-beta-CD, hydroxypropyl-beta-CD and the native beta- and gamma-CDs were examined. Among the nine CDs tested, the maleic acid derivative of beta-CD gave the most interesting performances, since it resolved the atropisomers of BNA and BNHP in the same electrophoretic run at pH 4.0. It resolved the BNA racemate also at pH 6.5. Both the negatively charged CD tested were found to resolve anionic BNHP enantiomers, while positively charged CDs did not with cationic BNA. Several of the CDs investigated in this work were found to resolve the BNHP racemate, although at nonoptimal concentration. None of the experimented CDs was found to resolve the electrically neutral BN atropisomers pair at the three pHs considered, while some among these nine, experimented in a previous work, did so at higher pH.     

Combination of cyclodextrins and polymeric surfactants for chiral separations

A cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) method was applied to the enantioseparation of three binaphthyl derivatives using neutral CDs (i.e., beta- and gamma-CD) in combination with various chiral amino acid-based polymeric surfactants (PSs). Both the D- and L-configurations of poly(sodium N-undecanoyl alaninate), poly(sodium N-undecanoyl leucinate), and poly(sodium N-undecanoyl valinate) (poly(L-SUV)) were synthesized. The retention behavior of the three binaphthyl derivatives under optimum electrophoretic conditions using a single chiral additive (PS or CD) is discussed. In addition, the effect of CD cavity size and stereochemical configuration of polymeric surfactants on selectivity (alpha) and resolution (Rs) was investigated. The enantioseparation of (+/-)1,1'-binaphthyl-2,2'-diamine gave a reversal of enantiomeric order when using beta-CD in combination with any of the three D-configuration PS. However, better enantioseparation is obtained when using the corresponding L-configuration PS with beta-CD. A reversal of migration order (RMO) for the enantiomers of (+/-)1,1'-bi-2-naphthol was observed upon the addition of 10 mM gamma-CD to poly(L-SUV). However, no RMO of (+/-)1,1'-bi-2-naphthol was seen when either beta-CD or gamma-CD was combined with D-PS. The enantiomers of (+/-)1,1'-binaphthyl-2,2'-diyl hydrogen phosphate showed little enantioselective behavior toward the PS alone. However, combined D- or L-PS and beta-CD or gamma-CD systems gave increased Rs and alpha values. The chiral recognition of binaphthyl derivatives observed resulting from the various combinations of two chiral selectors is discussed.     

七-(2,6-二-O-甲基)-β-环糊精对1,1'-联萘酚对映体手性识别的电喷雾质谱研究

利用电喷雾质谱研究了β-环糊精、七-(2,6-二-O-甲基)-β-环糊精作为手性识别试剂对1,1'-联萘酚对映体的手性识别效应. 实验结果表明, 在气相中, β-环糊精与七-(2,6-二-O-甲基)-β-环糊精都可以与联萘酚形成非共价复合物. 对形成的复合物的串联质谱研究表明, β-环糊精不能识别联萘酚对映体, 而七-(2,6-二-O-甲基)-β-环糊精对联萘酚对映体有较强的手性识别效应. 进一步研究表明七-(2,6-二-O-甲基)-β-环糊精与联萘酚对映体混合比例以及CID能量对于手性识别并无影响.     

Steric effects on the enantiodiscrimination of diproline chiral stationary phases in the resolution of racemic compounds

Eight diproline chiral stationary phases with different end-capping groups were prepared and evaluated for the enantio-selective resolution of 41 racemic analytes. The end-capping group on the N-terminal of the peptide proved to be important as the chiral separation efficiency was decreased significantly without it. In general, increasing steric bulkiness near the N-terminal of diproline increases the enantioselectivity. Electronic structures of the end-capping groups are also important. One stationary phase with an adamantanecarbonyl capping group was found to provide both higher average separation and resolution factors than our previous leader. Three other stationary phases with 2-methylpropanoyl, cyclopropanecarbonyl and cyclobutanecarbonyl end capping groups were found to provide comparable average separation factor but higher resolution factors than our previous leader.     

Well-defined enantiopure 1,1'-binaphthyl-based oligomers: synthesis,structure, photophysical properties,and chiral sensing

A series of well-defined enantiopure 1,1'-binaphthyl-based oligomers linked through their 6,6'-positions, ranging from quaternaphthol to decanaphthol, have been synthesized by Suzuki and Stille coupling reactions. These novel oligonaphthyls have been characterized by (1)H and (13)C[(1)H] NMR spectroscopy and high-resolution mass spectrometry. A combination of X-ray structural and CD studies suggests that these oligonaphthyls adopt zigzag but not helical conformations. As the chain length increases, the compounds show enhanced fluorescence. The fluorescence intensity of oligonaphthols is almost 2 orders of magnitude higher than that of 1,1'-bi-2-naphthol and can be effectively and enantioselectively quenched with trans-1,2-diaminocyclohexane with an enantioselectivity factor of 1.24. The present work thus demonstrates the potential of constructing chiral sensory materials based on well-defined enantiopure oligonaphthols.     

N-alkoxyacrylamides as substrates for enantioselective Diels-Alder reactions

[reaction: see text] The use of N-alkoxyacrylamides as substrates for Lewis acid catalyzed Diels-Alder reactions has been examined. Enantioselectivities up to 92% ee have been achieved using very simple chiral Lewis acids prepared from triisobutylaluminum and 2,2-dimethyl-alpha,alpha,alpha',alpha'-tetra-1-naphthalenyl-TADDOL (1-NaphtTADDOL). The use of Yamamoto's Zn-BINOL, easily prepared from Et2Zn and 1,1'-bi-2-naphthol (BINOL), proved to be even more efficient, and enantioselectivities up to 96% ee were achieved.     

手性双提蓝钴卟啉配合物催化二氧化碳对环氧的不对称环加成（英文）

绿色化学是当今化学科学研究的前沿领域.仿生催化是绿色合成技术和方法学研究的一个重要方面.生物质和酶分子在酶催化转化过程中的"构-效"关系可以通过仿生催化进行模拟研究.CO_2作为温室气体的主要成分是造成全球气候变暖的主要因素,但它同时也是C1化学的重要原料.利用CO_2与有机环氧化合物通过偶联反应制备有机环碳酸酯或聚碳酸酯则是CO_2化学研究的热点之一,并已经取得了长足的进步.但是运用手性催化剂对此反应进行不对称环加成得到手性环碳酸酯的研究不多.本文首次设计并合成了具有双提篮结构的手性钴卟啉螯合物.其中的提篮部分由手性联萘酚(S或R)和L-苯丙氨酸组成,从卟啉骨架的meso位引入,首先制备了两种手性结构的自由卟啉配体(6a,7a);然后与醋酸钴反应得到两种二价钴卟啉手性配合物(6b,7b),加入醋酸后,通过空气氧化得到三价钴卟啉手性催化剂(6c,7c).采用紫外、红外光谱、质谱和核磁共振(包括二维NMR)等技术对得到的卟啉中间化合物、配合物和催化剂进行了详细的表征,确定了化合物的结构.将得到的三价钴卟啉配合物作为手性催化剂用于CO_2和环氧化合物的不对称环加成反应.结果表明,提篮的手性基团对小分子的环氧化合物环氧丙烷具有手性选择性,在低温-20°C下,可以得到大于50%的ee值.同时由于提篮与卟啉平面空间的有限性,导致分子体积较大的环氧化合物与CO_2的反应很慢,也没有发现其对环碳酸酯的对映选择性.我们相信本工作对于合成手性卟啉分子及其在不对称催化中的应用具有一定的意义.     

New amphiphilic aminosaccharide derivatives as chiral selectors in capillary electrophoresis

Two amphiphilic aminosaccharide derivatives were investigated as chiral selector additives in capillary electrophoresis. Each substance has a glucosamine backbone carrying three hydrocarbon chains as the hydrophobic region and three carboxylic groups as the hydrophilic region, which is an artificial biologically active compound. Using each compound as a chiral selector, the optical resolution of dansylated amino acids or new quinolone antibacterial agents (NQs) was observed. Increasing the concentration of the chiral selector or the ionic strength of running solution led to successful optical resolution. In consideration of the chemical structure of each selector and the migration behavior of the enantiomers, the resolution seemed to be based on micellar electrokinetic chromatography mode. Both selectors differed in their enantioselectivity for dansylated amino acids or NQs although the chemical structures were similar.     

Three-dimensional chiral imaging by sum-frequency generation

A sum-frequency generation (SFG) microscope that is sensitive toward molecular chirality was demonstrated for the first time. Optically active images of chiral 1,1'-bi-2-naphthol solutions were obtained with submicron spatial resolution. Three-dimensional sectioning capability of our microscope was also demonstrated. This optically active SFG microscopy can potentially become a powerful imaging technique for biological samples.     

Enantiomeric separation of alcohols and amines on a proline chiral stationary phase by gas chromatography

A new chiral stationary phase for gas chromatography was prepared by covalently attaching a diproline chiral selector that has proven to be effective in liquid chromatography to a methylhydrosiloxane-dimethylsiloxane copolymer. With this new chiral stationary phase for GC, racemic aromatic alcohols could be resolved without derivatization. Racemic aromatic and aliphatic amines could also be resolved after derivatization of the amino groups with trifluoroacetic anhydride or isopropyl isocyanate. On this stationary phase, the isopropyl isocyanate derivatives of amines showed higher enantioselectivity than the trifluoroacetic anhydride derivatives. In both the enantiomeric separations of alcohols and derivatized amines, the aromatic racemic analytes showed higher enantioselectivities than their aliphatic analogs. Some of the alpha-amino and alpha-hydroxy aromatic acids could also be separated after derivatization to N-trifluoroacetyl methyl esters for amino acids or O-trifluoroacetyl methyl esters for hydroxyl acids.     

LC Separation of Enantiomers on Silica-Bonded Thiostrepton Derivatives

The macrocyclic antibiotic thiostrepton has been structurally modified with achiral reagents containing aromatic groups and isocyanate or isothiocyanate-terminated linkages to improve its selectivity in the LC resolution of aromatic enantiomers in polar–organic mode. The enantiomer resolutions achieved could not be reproduced either with underivatized thiostrepton or with the rifamycin SV stationary phase prepared by use of the same reaction procedures. Maximum enantioselectivity was achieved by optimizing the number of achiral derivatizing groups attached to thiostrepton. Chromatographic data for resolution of enantiomers containing aromatic groups suggest that the enhanced resolution is highly dependent on the π–π interaction between the analyte and the chiral selector. A mechanistic study entailing resolution of amino acid derivatives also indicated that analyte structure affects the strength of the π–π interaction and is crucial for chiral recognition to be possible. Other effects, for example steric hindrance, dipole–dipole interaction, and hydrogen bonding with the isocyanate and isothiocyanate functional groups of reagents also facilitate resolution.