高效液相色谱法手性分离二茂铁衍生物

建立了4个单手性和3个双手性(含有手性中心和面手性)的二茂铁衍生物在Chiralpak IC(纤维素-三(3,5-二氯苯基氨基甲酸酯))和Chiralpak IE3(直链淀粉-三(3,5-二氯苯基氨基甲酸酯))手性固定相上的高效液相色谱分离方法。4个单手性二茂铁衍生物中有3个可以在Chiralpak IE3固定相上实现基线分离,另外1个则在Chiralpak IC手性固定相上实现基线分离。3个双手性二茂铁衍生物可在Chiralpak IC手性固定相上实现基线分离。研究表明,这两种手性固定相对二茂铁衍生物具有较好的手性识别作用,并且具有互补作用。这一研究结果可为手性二茂铁化合物的分离提供借鉴和参考。     

Asymmetric crystallization of bisguanidinobenzene derivatives

We show that the mono-N-methylated and -ethylated derivatives of the achiral compound bisguanidinobenzene undergo spontaneous asymmetric crystallization into a chiral form with chiral space group P2₁2₁2₁. The absolute configurations of the chiral crystals were determined by X-ray crystallography and correlated with circular dichroism (CD) spectra recorded in the solid state. The corresponding protonated and isopropylated derivatives, by contrast, afforded achiral crystals.     

Resolution of enantiomers by HPLC on cellulose derivatives

Summary Various polysaccharide derivatives, particularly cellulose derivatives, were synthesized and used as chiral stationary phases for optical resolution by HPLC after being adsorbed on macroporous silica gel. Cellulose triacetate (CTA-II), which was synthesized under homogeneous conditions, showed a chiral recognition ability for many racemates. Other cellulose derivatives such as cellulose tribenzoate (OB), cellulose-trisphenylcarbamate (OC), cellulose tribenzyl ether (OE), and cellulose tricinnamate (OK) also showed unique chiral recognition. Among other polysaccharide derivatives, curdlan triacetate was also exhibited an effective chiral recognition. Presented at the 15th International Symposium on Chromatography, Nürnberg, October 1984     

Preparation of polysaccharide derivatives and their chiral recognition mechanism

Several new phenylcarbamate derivatives of cellulose and amylose having fluoro and methyl groups or 4-trimethylsilyl substituent on the phenyl groups were prepared and their chiral recognition abilities as chiral stationary phases for HPLC were evaluated. These derivatives are soluble in chloroform and exhibit chiral discrimination in ¹H NMR spectroscopy. Based on the above results and molecular mechanics calculation of interaction energies between the derivatives and enantiomers, the mechanism of chiral discrimination is discussed.     

Lithiation of deoxypeganine and chiral synthesis of deoxypeganine derivatives

A method was developed for lithiation of deoxypeganine. The reaction of organolithium deoxypeganine derivatives with isobutyraldehyde and benzaldehyde to produce its derivatives was studied. A chiral synthesis of substituted deoxypeganines was performed. The synthesized diastereomers and enantiomers were separated successfully using HPLC and a chiral column.     

Diastereoselective electrochemical carboxylation of chiral alpha-bromocarboxylic acid derivatives: an easy access to unsymmetrical alkylmalonic ester derivatives

The diastereoselective electrochemical carboxylation of chiral N-(2-bromoacyl)oxazolidin-2-ones has been studied. This reaction was carried out by cathodic reduction of the C-Br bond, in the presence of carbon dioxide, followed by treatment with diazomethane. The yields and the diastereomeric ratio of the two epimeric alkylmalonic acid derivatives are strongly affected by various factors: solvent-supporting electrolyte system, temperature, electrode material, electrolysis conditions, oxazolidinone moiety. The higher yields (88%) were obtained starting from N-(2-bromopropionyl)-4R-phenyloxazolidin-2-one 1a, but with poor diastereoselectivity (61:39). The two epimers were easily separated by flash chromatography. The best results were achieved using a different chiral auxiliary: Oppolzer's camphor sultam. Starting from 1j a good yield in carboxylated product was obtained (80%) with excellent diastereoselectivity (98:2). These chiral alkylmalonic acid derivatives are valuable building blocks in the synthesis of molecules with biological activity and of chiral propane-1,3-diols derivatives.     

Application of tetraoxadiaza-crown ether derivatives as chiral selector modifiers in capillary electrophoresis

Two new diaza-crown ether derivatives (R-1, RS-1) have been synthesized from 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane and tested as potential chiral selectors in capillary electrophoresis (CE) for the chiral separation of five amino acid derivatives. The individual use of the selectors did not lead to chiral differentiation. However, they enhanced the enantioselective effect of different cyclodextrins in dual selector systems. In this paper, we report the effect of different substituted diaza-crown ether derivatives on the separation results obtained in dual systems with cyclodextrins.     

Chloromethylphenylcarbamate derivatives of cellulose as chiral stationary phases for high-performance liquid chromatography

A new class of eight chloromethylphenylcarbamate derivatives of cellulose was prepared by introducing both an electron-donating methyl group and an electron-withdrawing chloro group on to the phenyl moieties and their chiral recognition abilities were evaluated as chiral stationary phases (CSPs) for high-performance liquid chromatography. The superiority of these derivatives over dichloro- and dimethylphenylcarbamates of cellulose as CSPs was demonstrated for some racemic compounds. The elution order and enantioselectivity were greatly dependent on the positions of the substituents. Meta- and para-disubstituted derivatives showed higher chiral recognition than ortho- and meta- or para- disubstituted derivatives. The correlation between the chemical shifts of the N---H protons of the carbamate moieties and the enantiomer-resolving abilities of the derivatives is discussed. Some of the derivatives were effective CSPs in both normal- and reversed- phase conditions and could efficiently separate some chiral drug enantiomers.     

Enantioselective synthesis of fluorene derivatives by chiral N-triflyl phosphoramide catalyzed double Friedel-Crafts alkylation reaction

A highly efficient tandem double Friedel-Crafts reaction between indoles and 2-formylbiphenyl derivatives by chiral N-triflyl phosphoramide was realized. Under mild conditions, various 9-(3-indolyl) fluorene derivatives have been obtained in good yield and up to 94% ee. Comparing to their corresponding chiral phosphoric acids, chiral N-triflyl phosphoramides catalyzed reactions led to products with opposite absolute configuration.     

Enhanced chromatographic resolution of alcohol enantiomers as phosphate or phosphonate derivatives

Phosphate and phosphonate derivatives of chiral alcohols show enhanced resolution by HPLC using a chiral support. Labile derivatives were also prepared that allow separation and recovery of the corresponding alcohol after basic hydrolysis.     

Chirality induction of polyaniline derivatives through chiral complexation

Chirality induction of π-conjugated polyaniline derivatives was achieved by chiral complexation with chiral palladium(II) complexes. The crystal structure of the chiral conjugated complex with a model compound of the polyaniline, N,N-bis(4^′-dimethylaminophenyl)-1,4-benzoquinonediimine, revealed a chiral propeller twist conformation of the π-conjugated moiety.     

Organocatalytic enantioselective Friedel-Crafts reaction of pyrrole derivatives with imines

A highly enantioselective Friedel-Crafts reaction of pyrrole derivatives with N-acyl imines catalyzed by chiral phosphoric acids was developed. The reactions produced the pyrrole derivatives in high yields and enantioselectivity.     

Asymmetric synthesis and antiviral activity of novel chiral amino-pyrimidine derivatives

By using a chiral cinchona alkaloid-squaramide catalyst, a series of both enantiomers of novel amino-pyrimidine derivatives can be obtained in an enantioselective three-component one-pot Mannich reaction with high yields and excellent enantioselectivities. In addition, these chiral derivatives were found to exhibit higher antiviral activities against tobacco mosaic virus (TMV) in vivo than the commercial agent ningnanmycin. In particular, chiral compounds (R)-4b and (R)-4e showed excellent antiviral activity against TMV at a concentration of 500?μg/mL, with a curative activity of 56.8% and 55.2%, respectively, a protection activity of 69.1% and 67.1%, respectively, and an inactivation activity of 91.5% and 94.3%, respectively. These values are superior to those of the agent ningnanmycin (which has curative, protective, and inactivation activities of 52.9%, 62.8%, and 90.4%, respectively). The antiviral mechanisms and enhanced antiviral activities of these chiral derivatives are interesting subjects for future investigation.     

Novel cinchona alkaloid O9-hydrazide derivatives as chiral anion-exchange-type selectors: Synthesis and chromatographic evaluation

Summary Six new quinine (QN) O₉-hydrazide derivatives with different substituents have been synthesized and immobilized on porous silica gel for HPLC. The chiral resolving power of these anion-exchange-type chiral stationary phases (CSPs) has been investigated and compared with that of four carbamate QN derivatives with analogous substitution. The unsubstituted QN-hydrazide derivative was usually the best chiral selector of the hydrazide series. Among the substituted hydrazide derivatives the introduction of a tritylcarbonyl or atert-butylcarbonyl group at the β position of the hydrazide function improved chiral recognition by the resulting CSPs. Although carbamate functionality seemed to favour the resolution of the enantiomers of many of the racemic compounds tested, the hydrazide series resulted in better separations of the enantiomers of the DNP derivatives of amino acids and of certain acidic drugs of therapeutic interest, such as the profens. The selectivity factors of these types of compounds on these QN-hydrazide derivatives are the best yet obtained on QN-derived chiral selectors.     

Enantioselective synthesis of axially chiral hydroxy carboxylic acid derivatives by rhodium-catalyzed [2 + 2 + 2] cycloaddition

Axially chiral hydroxy carboxylic acid derivatives were successfully synthesized with high yields and ee values by the cationic rhodium(I)/axially chiral biaryl bisphosphine complex-catalyzed enantioselective [2 + 2 + 2] cycloaddition. Axially chiral hydroxy and dihydroxy carboxylic acid derivatives, bearing the aryl group at the ortho-position of the alkoxycarbonyl group, were also synthesized with high regio- and enantioselectivity.     

Design of chiral organocatalysts for practical asymmetric synthesis of amino acid derivatives

A series of structurally rigid, chiral quaternary ammonium salts and several chiral sec-amine catalysts derived from commercially available (R)- or (S)-binaphthol have been designed as new C(2)-symmetric chiral phase-transfer catalysts and chiral bifunctional amino-catalysts. These chiral organocatalysts have been successfully applied to the highly practical asymmetric synthesis of various amino acid derivatives.     

Chiral salen-metal derivatives of polyoxometalates with asymmetric catalytic and photocatalytic activities

Immobilization of the chiral salen-metal complex [Mn(III)(salen)(H(2)O)(2)ClO(4)] on the Keggin-type polyoxometalate (POM) skeletons leads to the isolation of POM derivatives functionalized with chiral salen-metal complexes, which represent the first examples of introducing chiral salen-metal complexes into the POM systems.     

Recent developments in the synthesis of prosophylline and its derivatives

Several synthetic efforts are reported towards the optically active (?)-prosophylline and (+)-prosophylline, and their derivatives. Interestingly and surprisingly, although only a few synthesis are reported for the parent molecules, there are more reports for the synthesis of their derivatives such as deoxoprosophyllines, deoxoprosopinines, deoxocassines etc. The three main strategies to procure these molecules in optically pure forms are by using (i) chiral synthons (ii) chiral auxiliaries and (iii) asymmetric catalysis. Among these, the chiral synthons are mainly utilized by a number of researchers. This review summarizes the recent developments in the synthesis of optically active prosophyllines and their derivatives, and covers the literature from the year 2000 onwards.     

Stereoselective electrochemical carboxylation: 2-phenylsuccinates from chiral cinnamic acid derivatives

Chiral 2-phenyl succinic ester derivatives have been obtained under mild conditions, in short times and with satisfactory yields by electrochemical reduction of chiral cinnamic acid derivatives under a CO2 atmosphere. When 4R-(diphenylmethyl)-oxazolidin-2-one was used as a chiral auxiliary the two diastereoisomers could be easily separated by flash chromatography and the R-isomer was obtained as major product.     

A catalytic asymmetric synthesis of chiral glycidic acid derivatives through chiral dioxirane-mediated catalytic asymmetric epoxidation of cinnamic acid derivatives

A novel and practical asymmetric synthesis of chiral glycidic acid derivatives involving methyl (2R,3S)-3-(4-methoxyphenyl)glycidate ((2R,3S)-2a), a key intermediate for diltiazem hydrochloride (1), was developed. Treatment of methyl (E)-4-methoxycinnamate ((E)-3a) with chiral dioxirane, generated in situ from a catalytic amount (5 mol %) of an 11-membered C(2)-symmetric binaphthyl ketone (R)-7a, provided (2R,3S)-2a in 92% yield and 80% ee. Other cinnamic acid esters and amides were epoxidized by the use of the same procedure to give the corresponding chiral glycidic acid derivatives with up to 95% yield and 92% ee. Higher enantioselectivities in the asymmetric epoxidation of (E)-cinnamates than that of (E)-stilbene derivatives were observed and were proposed to be attributed to a dipole-dipole repulsion between oxygen atoms of an ester group in the cinnamates and those of the lactone moieties in the binaphthyl dioxirane.