A novel C2 symmetric chiral stationary phase with N‐[(4‐Methylphenyl)sulfonyl]‐l‐leucine as chiral side chains

In this study, a series of chiral stationary phases based on N‐[(4‐methylphenyl)sulfonyl]‐l ‐leucine amide, whose enantiorecognition property has never been studied, were synthesized. Their enantioseparation abilities were chromatographically evaluated by 67 enantiomers. The chiral stationary phase derived from N‐[(4‐methylphenyl)sulfonyl]‐l ‐leucine showed much better enantioselectivities than that based on N‐(4‐methylbenzoyl)‐l ‐leucine amide. The construction of C₂ symmetric chiral structure greatly improved the enantiorecognition performance of the stationary phase. The C₂ symmetric chiral stationary phase exhibited superior enantioresolutions to other chiral stationary phases for most of the chiral analytes, especially for the chiral analytes with C₂ symmetric structures. By comparing the enantioseparations of the enantiomers with similar structures, the importance of hydrogen bond interaction, π–π interaction, and steric hindrance on enantiorecognition was elucidated. The enantiorecognition mechanism of trans‐N,N′‐(1,2‐diphenyl‐1,2‐ethanediyl)bis‐acetamide, which had an excellent separation factor on the C₂ symmetric chiral stationary phase, was investigated by ¹H‐NMR spectroscopy and 2D ¹H‐¹H nuclear overhauser enhancement spectroscopy.     

Enantioseparation of Novel Chiral Tetrahedral Clusters on an Amylosoe Tris-（3,5-dimethylphenylcarbamate） Chiral Stationary Phase by Normal Phase HPLC

Amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) coated on a kind of small particle silica gel was prepared. On this ADMPC chiral stationary phase (CSP), the direct enantiomeric separation of six novel chiral transition metal tetrahedral clusters has firstly been achieved using n-hexane as the mobile phase containing various alcohols as modifiers. The effect of mobile phase modifiers and the structural variation of the solutes on their retention factors (k‘) and resolutions (Rs) were investigated. The result suggests that not only the structure and concentration of alcohol in mobile phase, but also the structural differences in racemates can have a pronounced effect on enantiomeric separation. ADMPC-CSP is a suitable CSP for the optical resolution of chiral tetrahedral cluster by HPLC.     

HPLC enantioseparation of β2‐homoamino acids using crown ether‐based chiral stationary phase

RP high‐performance liquid chromatographic methods were developed for the enantioseparation of eleven unusual β²‐homoamino acids. The underivatized analytes were separated on a chiral stationary phase containing (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid as chiral selector. The effects of organic (alcoholic) and acidic modifiers, the mobile phase composition and temperature on the separation were investigated. The structures of the substituents in the α‐position of the analytes substantially influenced the retention and resolution. The elution sequence was determined in some cases: the S enantiomers eluted before the R enantiomers.     

Binding modes identification through molecular dynamic simulations: A case study with carnosine enantiomers and the Teicoplanin A2‐2‐based chiral stationary phase

In the present study, an in silico methodology able to define the binding modes adopted by carnosine enantiomers in the setting of the chiral recognition process is described. The inter‐ and intramolecular forces involved in the enantioseparation process with the Teicoplanin A2‐2 chiral selector and carnosine as model compound are successfully identified. This approach fully rationalizes, at a molecular level, the (S) < (R) enantiomeric elution order obtained under reversed‐phase conditions. Consistent explanations were achieved by managing molecular dynamics results with advanced techniques of data analysis. As a result, the time‐dependent identification of all the interactions simultaneously occurring in the chiral selector‐enantiomeric analyte binding process was obtained. Accordingly, it was found that only (R)‐carnosine is able to engage a stabilizing charge–charge interaction through its ionized imidazole ring with the carboxylate counter‐part on the chiral selector. Instead, (S)‐carnosine establishes intramolecular contacts between its ionized functional groups, that limit its conformational freedom and impair the association with the chiral selector unit.     

Cellulose tris‐(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase for the enantioseparation of drugs in supercritical fluid chromatography: comparison with HPLC

A cellulose tris‐(3,5‐dimethylphenylcarbamate)‐based chiral stationary phase was studied as a tool for the enantioselective separation of 21 selected analytes with different pharmaceutical and physicochemical properties. The enantioseparations were performed using supercritical fluid chromatography. The effect of the mobile phase composition was studied. Four different additives (diethylamine, triethylamine, isopropylamine, and trifluoroacetic acid) and isopropylamine combined with trifluoroacetic acid were tested and their influence on enantioseparation was compared. The influence of two different mobile phase co‐solvents (methanol and propan‐2‐ol) combined with all the additives was also evaluated. The best mobile phase compositions for the separation of the majority of enantiomers were CO₂/methanol/isopropylamine 80:20:0.1 v/v/v or CO₂/propan‐2‐ol/isopropylamine/trifluoroacetic acid 80:20:0.05:0.05 v/v/v/v. The best results were obtained from the group of basic β‐blockers. A high‐performance liquid chromatography separation system composed of the same stationary phase and mobile phase of similar properties prepared as a mixture of hexane/propan‐2‐ol/additive 80:20:0.1 v/v/v was considered for comparison. Supercritical fluid chromatography was found to yield better results, i.e. better enantioresolution for shorter analysis times than high‐performance liquid chromatography. However, examples of enantiomers better resolved under the optimized conditions in high‐performance liquid chromatography were also found.     

Mechanistic Investigation of the Dipolar [2+2] Cycloaddition–Cycloreversion Reaction between 4‐(N,N‐Dimethylamino)phenylacetylene and Arylated 1,1‐Dicyanovinyl Derivatives To Form Intramolecular Charge‐Transfer Chromophores

The kinetics and mechanism of the formal [2+2] cycloaddition–cycloreversion reaction between 4‐(N,N‐dimethylamino)phenylacetylene ( 1 ) and para‐substituted benzylidenemalononitriles 2 b – 2 l to form 2‐donor‐substituted 1,1‐dicyanobuta‐1,3‐dienes 3 b – 3 l via the postulated dicyanocyclobutene intermediates 4 b – 4 l have been studied experimentally by the method of initial rates and computationally at the unrestricted B3LYP/6‐31G(d) level. The transformations were found to follow bimolecular, second‐order kinetics, with ${{\rm{\Delta }}H_{{\rm{exp}}}^{ {\ne} } }$ =13–18 kcal mol^?1, ${{\rm{\Delta }}S_{{\rm{exp}}}^{ {\ne} } }$ ≈?30 cal K^?1 mol^?1, and ${{\rm{\Delta }}G_{{\rm{exp}}}^{ {\ne} } }$ =22–27 kcal mol^?1. These experimental activation parameters for the rate‐determining cycloaddition step are close to the computational values. The rate constants show a good linear free energy relationship (ρ=2.0) with the electronic character of the para‐substituents on the benzylidene moiety in dimethylformamide (DMF), which is indicative of a dipolar mechanism. Analysis of the computed structures and their corresponding solvation energies in acetonitrile suggests that the rate‐determining attack of the nucleophilic, terminal alkyne carbon onto the dicyanovinyl electrophile generates a transient zwitterion intermediate with the negative charge developing as a stabilized malononitrile carbanion. The computational analysis predicted that the cycloreversion of the postulated dicyanocyclobutene intermediate would become rate‐determining for 1,1‐dicyanoethene ( 2 m ) as the electrophile. The dicyanocyclobutene 4 m could indeed be isolated as the key intermediate from the reaction between alkyne 1 and 2 m and characterized by X‐ray analysis. Facile first‐order cycloreversion occurred upon further heating, yielding as the sole product the 1,1‐dicyanobuta‐1,3‐diene 3 m .     

High‐performance liquid chromatographic enantioseparation of fluorinated cyclic β3‐amino acid derivatives on polysaccharide‐based chiral stationary phases. Comparison with nonfluorinated counterparts

The stereoisomers of five fluorinated cyclic β³‐amino acid derivatives and their nonfluorinated counterparts were separated on chiral stationary phases containing as chiral selectors cellulose tris‐(3,5‐dimethylphenyl carbamate), cellulose tris‐(3‐chloro‐4‐methylphenyl carbamate), cellulose tris‐(4‐methylbenzoate), cellulose tris‐(4‐chloro‐3‐methylphenyl carbamate), amylose tris‐(3,5‐dimethylphenyl carbamate) or amylose tris‐(5‐chloro‐2‐methylphenyl carbamate). The enantioseparations were carried out in normal‐phase mode with n‐hexane/alcohol/alkylamine mobile phases in the temperature range 5–40 °C. The effects of the mobile phase composition, the nature and concentration of the alcohol and alkylamine additives, the structures of the analytes and temperature on the separations were investigated. Thermodynamic parameters were calculated from plots of ln α vs. 1/T. The Δ(ΔH°) values ranged between ?5.0 and +1.6 kJ/mol, while Δ(ΔS°) varied between ?12.6 and +5.7 J/mol/K. The enantioseparation was enthalpically controlled, the retention factor and the separation factor decreasing with increasing temperature, but entropically controlled separation was also observed. The elution sequence was determined for all of the investigated analytes. Copyright © 2016 John Wiley & Sons, Ltd.     

Preparation and evaluation of a chiral HPLC stationary phase based on cone calix[4]arene functionalized at the upper rim with l‐alanine units

Here we report a new chiral stationary phase (CSP) immobilized on silica gel based on cone calix[4]arene functionalized at the upper rim with two l ‐alanine units as new chiral selector that has been used in high‐performance liquid chromatography. The CSP was prepared by covalently bonding the allyl groups at the lower rim of calix[4]arene to silica gel by thiol‐ene click chemistry reaction. Elemental analysis of the CSP showed that 120 μmol of chiral selector bonded per gram of silica gel. 1‐Hexene was used for end‐capping of unreacted mercapto groups on silica gel. Since the CSP is chemically bonded to the silica, it can be used in the normal‐phase and reversed‐phase mode and with halogenated solvents as mobile phases, if desired. The chromatographic performance of the CSP was evaluated in the enantioseparation of the 3,5‐dinitrobenzoyl derivatives of some amino acids, diclofop‐methyl and dl ‐mandelic acid.     

(E)‐3‐{4‐[(7‐Chloroquinolin‐4‐yl)oxy]‐3‐methoxyphenyl}‐1‐(4‐methylphenyl)prop‐2‐en‐1‐one: a ladder‐like structure resulting solely from π–π stacking interactions

In the title compound, C₂₆H₂₀ClNO₃, the quinoline fragment is nearly orthogonal to the adjacent aryl ring, while the rest of the molecular skeleton is close to being planar. The crystal structure contains no hydrogen bonds of any sort, but there are two π–π stacking interactions present. One, involving the quinoline ring, links molecules related by inversion, while the other, involving the two nonfused aryl rings, links molecules related by translation, so together forming a ladder‐type arrangement