Utilization of (18‐Crown‐6)‐2,3,11,12‐tetracarboxylic Acid as a Chiral NMR Solvating Agent for Diamines and β‐Amino Acids

The compound (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid was evaluated as a chiral nuclear magnetic resonance (NMR) solvating agent for a series of diamines and bicyclic β‐amino acids. The amine must be protonated for strong association with the crown ether. An advantage of (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid over many other crown ethers is that it undergoes a neutralization reaction with neutral amines to form the protonated species needed for binding. Twelve primary diamines in neutral and protonated forms were evaluated. Diamines with aryl and aliphatic groups were examined. Some are atropisomers with equivalent amine groups. Others have two nonequivalent amine groups. Association equilibria for these systems are complex, given the potential formation of 2:1, 1:1, and 1:2 crown‐amine complexes and given the various charged species in solution for mixtures of the crown ether with the neutral amine. The crown ether produced enantiomeric differentiation in the ¹H NMR spectrum of one or more resonances for every diamine substrate. Also, a series of five bicyclic β‐amino acids were examined and (18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid caused enantiomeric differentiation in the ¹H NMR spectrum of three or more resonances of each compound. Chirality 27:708–715, 2015. © 2015 Wiley Periodicals, Inc.     

Liquid chromatographic direct resolution of flecainide and its analogs on a chiral stationary phase based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

Flecainide, an antiarrythmic agent, and its analogs were resolved on a high performance liquid chromatographic chiral stationary phase (CSP) based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid with the use of a mobile phase consisting of methanol‐acetonitrile‐trifluoroacetic acid‐triethylamine (80/20/0.1/0.3, v/v/v/v). The chiral resolution was quite successful, the separation factors (α) and the resolutions (R_S) for 20 analytes including flecainide being in the range of 1.19–1.82 and 1.73–6.80, respectively. The ortho‐substituent of the benzoyl group of analytes was found to cause decrease in the retention times of analytes probably because of the conformational deformation of analytes originated from the steric hindrance exerted by the ortho‐substituent. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Liquid Chromatographic Resolution of Mexiletine and Its Analogs on Crown Ether‐Based Chiral Stationary Phases

Mexiletine, an effective class IB antiarrhythmic agent, and its analogs were resolved on three different crown ether‐based chiral stationary phases (CSPs), one (CSP 1 ) of which is based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid and the other two (CSP 2 and CSP 3 ) are based on (3,3’‐diphenyl‐1,1’‐binaphthyl)‐20‐crown‐6. Mexiletine was resolved with a resolution (R_S) of greater than 1.00 on CSP 1 and CSP 3 containing residual silanol group‐protecting n‐octyl groups on the silica surface, but with a resolution (R_S) of less than 1.00 on CSP 2 . The chromatographic behaviors for the resolution of mexiletine analogs containing a substituted phenyl group at the chiral center on the three CSPs were quite dependent on the phenoxy group of analytes. Namely, mexiletine analogs containing 2,6‐dimethylphenoxy, 3,4‐dimethylphenoxy, 3‐methylphenoxy, 4‐methylphenoxy, and a simple phenoxy group were resolved very well on the three CSPs even though the chiral recognition efficiencies vary with the CSPs. However, mexiletine analogs containing 2‐methylphenoxy group were not resolved at all or only slightly resolved. Among the three CSPs, CSP 3 was found to show the highest chiral recognition efficiencies for the resolution of mexiletine and its analogs, especially in terms of resolution (R_S). Chirality 26:272–278, 2014. © 2014 Wiley Periodicals, Inc.     

Enantiomeric Discrimination of Isoxazoline Fused β‐amino Acid Derivatives using (18‐Crown‐6)‐2,3,11,12‐tetracarboxylic Acid as a Chiral NMR Solvating Agent

(18‐Crown‐6)‐2,3,11,12‐tetracarboxylic acid is a useful chiral NMR solvating agent for isoxazoline‐fused β‐amino acid derivatives. Isoxazoline substrates are analyzed as their hydrochloride salts in methanol‐d₄. The crown ether and substrate associate through the formation of three hydrogen bonds between the protonated amine and crown ether oxygen atoms. Enantiomeric discrimination is observed for two or more resonances of every substrate. At least one of these resonances is free of overlap with other resonances in the spectrum and has large enough enantiomeric discrimination to enable the determination of enantiomeric purity. 2D COSY methods can be used to identify additional resonances that exhibit enantiomeric discrimination in the NMR spectrum. Chirality, 25:48‐53, 2013.© 2012 Wiley Periodicals, Inc.     

High‐Performance Liquid Chromatographic Enantioseparation of Unusual Isoxazoline‐Fused 2‐Aminocyclopentanecarboxylic Acids on (+)‐(18‐Crown‐6)‐2,3,11,12‐Tetracarboxylic Acid‐Based Chiral Stationary Phases

The enantiomers of four unusual isoxazoline‐fused 2‐aminocyclopentanecarboxylic acids were directly separated on chiral stationary phases containing (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid as chiral selector. The nature of the alcoholic modifier (MeOH, EtOH, IPA) exerted a great effect on the retention, whereas the selectivity and resolution did not change substantially. Two types of dependence of retention on alcohol content were detected: k₁ increased continuously with increasing alcohol content or a U‐shaped retention curve was observed. A comparison of the chromatographic data obtained with HCOOH, AcOH, TFA, HClO₄, H₂SO₄, or H₃PO₄ as acidic modifier at a constant concentration demonstrated that in most cases, larger k values were obtained on the application of AcOH or HCOOH, and an increase of the acid content resulted in a decrease of retention. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes and selector. The sequence of elution of the enantiomers was determined in all cases. Chirality 24:817‐824, 2012. © 2012 Wiley Periodicals, Inc.     

Enantiomeric separation of Novel Psychoactive Substances by capillary electrophoresis using (+)‐18‐crown‐6‐tetracarboxylic acid as chiral selector

In the recent years, hundreds of Novel Psychoactive Substances (NPS) have entered both the European and the global drug market. These drugs, which are mainly used for recreational matters, have caused serious social problems. Every year, the spectrum of these misused drugs is enlarged by new derivatives, which are produced by modifications of basic structures of already well‐known substances. Additionally, a lot of them possess a stereogenic center which leads to 2 enantiomeric forms. The fact that the pharmacological effects and potencies of the enantiomers of these chiral NPS may differ can be assumed from a broad spectrum of active pharmaceutical ingredients. For this reason, analytical method development regarding enantiomeric separation for these classes of substances is of great pharmaceutical and medical interest. The aim of this work was to create an easy‐to‐prepare chiral capillary electrophoresis method for the enantioseparation of NPS which contains a primary amino group by means of (+)‐18‐crown‐6‐tetracarboxylic acid as chiral selector. Novel Psychoactive Substances were purchased at various Internet stores or represent samples seized by Austrian police. The effects of selector concentration, the electrolyte composition, and the addition of organic modifiers to the background electrolyte on enantioseparation were investigated. Under optimized conditions, the use of 20‐mM (+)‐18‐crown‐6‐tetracarboxylic acid, 10‐mM Tris, and 30‐mM citric acid buffer at pH 2.10 turned out to be effective. Fifteen of 24 tested NPS were resolved in their enantiomers within 15 minutes. It was found that all NPS were traded as racemic mixtures.     

Comparison of Chiral Separations of Aminophosphonic Acids and Their Aminocarboxylic Acid Analogs Using a Crown Ether Column

Crown ethers are capable of complexing with primary amines and have been utilized in chromatography to separate amino acid racemates. This application has been extended to resolve (1‐amino‐1‐phenylmethyl)phosphonic acid and (1‐aminoethyl)phosphonic acid racemates, along with their aminocarboxylic acid analogs (2‐phenylglycine and alanine, respectively), via a ChiroSil RCA crown ether based chiral stationary phase. Effects of the organic modifier, temperature, and acid type and concentration on retention and selectivity were also investigated. Trends in retention and selectivity varied between aminophosponic acids and their aminocarboxylic analogs. Computer modeling and ¹H NMR analyses were performed to potentially gain a better understanding of interactions of the aforementioned molecules with the ChiroSil RCA chiral stationary phase. Theoretical predictions of the most stable conformations for (R)‐ and (S)‐enantiomers were compared to elution order; it was found that the elution order agreed with molecular modeling such that the longest retention correlated with the predicted most stable complex between the enantiomer and crown ether. ¹H NMR demonstrated interactions of aminophosphonic and aminocarboxylic racemates with (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid in solution and was utilized to determine enantiomeric excess of (1‐amino‐1‐phenylmethyl)phosphonic acid after its enantioenrichment via crystallization through diastereomeric salt formation with the crown ether followed by filtration. Chirality 25:369–378, 2013. © 2013 Wiley Periodicals, Inc.     

New chiral stationary phases based on (R)‐1‐naphthylethylamine bound to 2,4,5,6‐tetrachloro‐1,3‐dicyanobenzene

Chiral functionalization of 2,4,5,6‐tetrachloro‐1,3‐dicyanobenzene (1) by regioselective nucleophilic substitution of one or two chlorine atoms by optically pure (R)‐(+)‐1‐naphthylethylamine (NEA), or by a glycine unit as a spacer to (R)‐NEA, enables the preparation of brush‐type chiral selectors (2, 3, 9, 13). By the introduction of the 3‐aminopropyltriethoxysilyl (APTES) group, reactive intermediates 4a/b, 5, 10a/b, and 14a/b are obtained ( a/b indicate a mixture of regioisomers with APTES in 6‐ and 2‐position). Binding of these to silica gel afforded four novel chiral stationary phases (CSPs) 6, 7, 15, and 16. HPLC columns containing CSPs with (R)‐NEA directly linked to polysubstituted aromatic ring (6, 7) are not very effective in resolution of most of the 23 racemic analytes, whereas the columns with distant π‐basic subunits (15, 16) exhibited higher resolving efficacy, in particular towards the isopropyl esters of racemic N‐3,5‐dinitrobenzoyl‐α‐amino acids. Effective resolution of test racemates reveals the importance of the presence of the hydrogen bond donor amido group and the distance between the persubstituted benzene ring in 1 and the π‐basic naphthalene ring of (R)‐NEA. Chirality 11:722–730, 1999. © 1999 Wiley‐Liss, Inc.     

Liquid chromatographic resolution of 3-amino-1,4-benzodiazepin-2-ones on crown ether-based chiral stationary phases

3-Amino-5-phenyl (or 5-methyl)-1,4-benzodiazepin-2-ones, which are chiral precursors of anti-respiratory syncytial virus active agents, were resolved on three different chiral stationary phases (CSPs) based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid or (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6. Among the three CSPs, the CSP that is based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 and containing residual silanol group-protecting n-octyl groups on the silica surface was found to be most effective with the use of 80% ethanol in water containing perchloric acid (10 mM) and ammonium acetate (1.0 mM) as a mobile phase. The separation factors (α) and resolutions (R(S) ) were in the range of 1.90-3.21 and 2.79-5.96, respectively. From the relationship between the analyte structure and the chromatographic resolution behavior, the chiral recognition mechanism on the CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid was proposed to be different from that on the CSP based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6. In addition, the chromatographic resolution behavior of the most effective CSP was investigated as a function of the composition of aqueous mobile phase containing organic and acidic modifier and ammonium acetate.     

Crystallographic studies for the chiral recognition of the novel chiral stationary phase derived from (+)‐(R)‐18‐crown‐6 tetracarboxylic acid

Chiral discrimination observed in high‐performance liquid chromatography (HPLC) with the novel chiral stationary phase (CSP‐18C6I) derived from (+)‐(R)‐18‐crown‐6 tetracarboxylic acid [(+)‐18C6H₄] was investigated by X‐ray crystallographic analysis of the complex composed of the R‐enantiomer of 1‐(1‐naphthyl)ethylamine (1‐NEA) and (+)‐18C6H₄. Mixtures of 1‐NEA (the R‐ or S‐enantiomer) and (+)‐18C6H₄ were dissolved in methanol‐water (1:1) solution and allowed to stand for crystallization. The R‐enantiomer crystallized with (+)‐18C6H₄ as a co‐crystal, although the S‐enantiomer did not. This result was in good agreement with the enantiomer elution order of 1‐NEA in CSP‐18C6I. The apparent binding constants (K_a) of the enantiomers to the (+)‐18C6H₄ obtained from ¹H‐NMR experiments also supported the above‐mentioned result. The X‐ray crystal structure of the 1:1 complex of the R‐enantiomer and (+)‐18C6H₄ indicated the four sets of hydrogen bond association between the naphthylethylammonium cation and oxygen of polyether ring or carbonyl group of (+)‐18C6H₄. Chirality 11:173–178, 1999. © 1999 Wiley‐Liss, Inc.     

Liquid Chromatographic Resolution of Amino Acid Esters of Acyclovir Including Racemic Valacyclovir on Crown Ether‐Based Chiral Stationary Phases

Valacyclovir, a potential prodrug for the treatment of patients with herpes simplex and herpes zoster, and its analogs were resolved on two chiral stationary phases (CSPs) based on (3,3’‐diphenyl‐1,1’‐binaphthyl)‐20‐crown‐6 covalently bonded to silica gel. In order to find out an appropriate mobile phase condition, various mobile phases consisting of various organic modifiers in water containing various acidic modifiers were applied to the resolution of valacyclovir and its analogs. When 30% acetonitrile in water containing any of 0.05 M, 0.10 M, or 0.15 M perchloric acid was used as a mobile phase, valacyclovir and its analogs were resolved quite well on the two CSPs with the separation factors (α) in the range of 2.49 ~ 6.35 and resolutions (R_S) in the range of 2.95 ~ 12.21. Between the two CSPs, the CSP containing residual silanol protecting n‐octyl groups on the silica surface was found to be better than the CSP containing residual silanol groups. Chirality 27:268–273, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis and Application of C2 and C3 Symmetric (R)‐Phenylglycinol‐Derived Chiral Stationary Phases

A C3 symmetric (R)‐phenylglycinol N‐1,3,5‐benzenetricarboxylic acid‐derived chiral stationary phase (CSP) and three C2 symmetric (R)‐phenylglycinol CSPs were newly synthesized using o‐, m‐, and p‐phthaloyl dichlorides. © 2016 Wiley Periodicals, Inc. These CSPs were used to compare the resolution of 25 chiral samples using a previously reported 3,5‐dinitrobenzoyl (R)‐phenylglycinol‐derived CSP. Even though all CSPs have the same chiral moiety, the C3 symmetric CSP showed the best resolution. Chirality 28:186–191, 2016.© 2016 Wiley Periodicals, Inc.     

Comparative studies between covalently immobilized and coated chiral stationary phases based on polysaccharide derivatives for enantiomer separation of N‐protected α‐amino acids and their ester derivatives

Liquid chromatographic enantiomer separation of several N‐benzyloxycarbonyl (CBZ) and N‐tert‐butoxycarbonyl (BOC) α‐amino acids and their corresponding ethyl esters was performed on covalently immobilized chiral stationary phases (CSPs) (Chiralpak IA and Chiralpak IB) and coated‐type CSPs (Chiralpak AD and Chiralcel OD) based on polysaccharide derivatives. The solvent versatility of the covalently immobilized CSPs in enantiomer separation of N‐CBZ and BOC‐α‐amino acids and their ester derivatives was shown and the chromatographic parameters of their enantioselectivities and resolution factors were greatly influenced by the nature of the mobile phase. In general, standard mobile phases using 2‐propanol and hexane on Chiralpak IA showed fairly good enantioselectivities for resolution of N‐CBZ and BOC‐α‐amino acids and their esters. However, 50% MTBE/hexane (v/v) for resolution of N‐CBZ‐α‐amino acids ethyl esters and 20% THF/hexane (v/v) for resolution of N‐BOC‐α‐amino acids ethyl esters afforded the greatest enantioselectivities on Chiralpak IA. Also, liquid chromatographic comparisons of the enantiomer resolution of these analytes were made on amylose tris(3,5‐dimethylphenylcarbamate)‐derived CSPs (Chiralpak IA and Chiralpak AD) and cellulose tris(3,5‐dimethylphenylcarbamate)‐derived CSPs (Chiralpak IB and Chiralcel OD). Chiralpak AD and/or Chiralcel OD showed the highest enantioselectivities for resolution of N‐CBZ‐α‐amino acids and esters, while Chiralpak AD or Chiralpak IA showed the highest resolution of N‐BOC‐α‐amino acids and esters. Chirality 2009. © 2008 Wiley‐Liss, Inc.     

Synthesis of dendrimer‐type chiral stationary phases based on the selector of (1S,2R)‐(+)‐2‐Amino‐1,2‐diphenylethanol derivate and their enantioseparation evaluation by HPLC

In our recent work, a series of dendritic chiral stationary phases (CSPs) were synthesized, in which the chiral selector was L‐2‐(p‐toluenesulfonamido)‐3‐phenylpropionyl chloride (selector I), and the CSP derived from three‐generation dendrimer showed the best separation ability. To further investigate the influence of the structures of dendrimer and chiral selector on enantioseparation ability, in this work, another series CSPs ( CSPs 1‐4 ) were prepared by immobilizing (1S,2R)‐1,2‐diphenyl‐2‐(3‐phenylureido)ethyl 4‐isocyanatophenylcarbamate (selector II) on one‐ to four‐generation dendrimers that were prepared in previous work. CSPs 1 and 4 demonstrated the equivalent enantioseparation ability. CSPs 2 and 3 showed the best and poorest enantioseparation ability respectively. Basically, these two series of CSPs exhibited the equivalent enantioseparation ability although the chiral selectors were different. Considering the enantioseparation ability of the CSP derived from aminated silica gel and selector II is much better than that of the one derived from aminated silica gel and selector I, it is believed that the dendrimer conformation essentially impacts enantioseparation. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Chiral Recognition of N‐Phthaloyl,N‐Tetrachlorophthaloyl,and N‐Naphthaloyl α‐Amino Acids and Their Esters on Polysaccharide‐Derived Chiral Stationary Phases

Enantiomeric separations of N‐phthaloyl (N‐PHT), N‐tetrachlorophthaloyl (N‐TCPHT), and N‐naphthaloyl (N‐NPHT) α‐amino acids and their esters were examined on several kinds of polysaccharide‐derived chiral stationary phases (CSPs). Resolution capability of CSPs was greater Chiralcel OF than the others for N‐PHT and N‐NPHT α‐amino acids and their esters. In N‐TCPHT α‐amino acids and their esters, good enantioselectivities showed Chiralcel OG for N‐TCPHT α‐amino acids, Chiralpak AD for N‐TCPHT α‐amino acid methyl esters, and Chiralcel OD for N‐TCPHT α‐amino acid ethyl esters, respectively. From the results of liquid chromatography and computational chemistry, it is concluded that l ‐form is preferred and more retained with electrostatic interaction in case of interaction between N‐PHT α‐amino acid derivatives and Chiralcel OF, N‐TCPHT α‐amino acid derivatives and Chiralcel OD, and N‐NPHT α‐amino acid derivatives and Chiracel OF. On the other hand, d ‐form is preferred and more retained with van der Waals interaction in case of interaction between N‐TCPHT α‐amino acid ester derivatives and Chiralcel OG and Chiralpak AD. Chirality 24:1037–1046, 2012. © 2012 Wiley Periodicals, Inc.     

Chiral separation on various modified amino alcohol‐derived HPLC chiral stationary phases

3,5‐Dinitrobenzoyl chloride was previously used for the preparation of (R)‐phenylglycinol‐ and (S)‐leucinol‐derived chiral stationary phases. In this study, 3,5‐bis(trifluoromethyl)benzoyl chloride, 2‐furoyl chloride, 2‐theonyl chloride, 10,11‐dihydro‐5H‐dibenzo[b,f]azepine‐5‐carbonyl chloride, diphenylcarbamoyl chloride, and 1‐adamantanecarbonyl chloride were used to prepare six new phenylglycinol‐derived chiral stationary phases (CSPs) and five new leucinol‐derived CSPs. Using these 11 CSPs, chiral separation of nine π‐acidic amino acid derivatives and five π‐basic compounds was performed, and the separation results were compared. An adamantyl‐derived CSP showed good separation. Chirality 28:276–281, 2016. © 2016 Wiley Periodicals, Inc.     

Simple Resolution of Enantiomeric NMR Signals of α‐Amino Acids by Using Samarium(III) Nitrate With L‐Tartarate

Readily available L‐tartaric acid, which is a bidentate ligand with two chiral centers forming a seven‐membered chelate ring, was applied to the chiral ligand for the chiral nuclear magnetic resonance (NMR) shift reagent of samarium(III) formed in situ. This simple method does not cause serious signal broadening in the high magnetic field. Enantiomeric ¹³C and ¹H NMR signals and enantiotopic ¹H NMR signals of α‐amino acids were successfully resolved at pH 8.0 and the 1:3 molar ratio of Sm(NO₃)₃:L‐tartaric acid. It is elucidated that the enantiomeric signal resolution is attributed to the anisotropic magnetic environment for the enantiomers induced by the chiral L‐tartarato samarium(III) complex rather than differences in stability of the diastereomeric substrate adducts. The present ¹³C NMR signal resolution was also effective for the practical simultaneous analysis of plural kinds of DL‐amino acids. Chirality 27:353–357, 2015.© 2015 Wiley Periodicals, Inc.     

Guest-dependent conformation of 18-crown-6 tetracarboxylic acid: relation to chiral separation of racemic amino acids

(+)-18-crown-6 tetracarboxylic acid (18C6H(4)) has been used as a chiral selector for various amines and amino acids. To further clarify the structural scaffold of 18C6H(4) for chiral separation, single crystal X-ray analysis of its glycine(+) (1), H3O+ (2), H5O2+ (3), NH4+ (4), and 2CH3NH3+ (5) complexes was performed and the guest-dependent conformation of 18C6H(4) was investigated. The crown ether ring of 18C6H4 in 3, 4, and 5 took a symmetrical C2 or C2-like conformation, whereas that in 1 and 2 took an asymmetric C1 conformation, which is commonly observed in complexes with various optically active amino acids. The overall survey of the present and related complexes suggests that the molecular conformation of 18C6H4 is freely changeable within an allowable range, depending on the molecular shape and interaction mode with the cationic guest. On the basis of the present results, we propose the allowable conformational variation of 18C6H4 and a possible transition pathway from its primary conformation to the conformation suitable for chiral separation of racemic amines and amino acids.     

Chiral Pool‐Based Synthesis of Naphtho‐Fused Isocoumarins

A variety of chiral derivatives of benzo[d]naphtho[1,2‐b]pyran‐6‐one were prepared in a single step by Et₃N‐mediated condensation of homophthalic anhydride with different derivatives of (S)‐amino acid chlorides at –5 °C by employing a chiral pool methodology. Chirality 27:951–957, 2015. © 2015 Wiley Periodicals, Inc.     

Comparative HPLC Enantioseparation of Thirty‐Six Aromatic Compounds on Four Columns of the Lux® Series: Impact of Substituents,Shapes and Electronic Properties

With the aim to define a combined computational/chromatographic empirical approach useful for the high‐performance liquid chromatography (HPLC) method development of new chiral compounds, 36 racemic aromatic compounds with different chemical structures were used as test probes on four polysaccharide‐based chiral stationary phases (CSPs) of the Lux series, namely Lux Cellulose‐1, Lux Cellulose‐2, Lux Cellulose‐4, and Lux Amylose‐2, using classical n‐hexane/2‐propanol mixtures as mobile phase. Electrostatic potential surfaces (EPSs) determined using Density Functional Theory (DFT) calculations were used to derive size, shape, and electronic properties of each analyte. Then a comparative HPLC screening was carried out in order to evaluate the impact of substituents, shapes, and electronic properties of the analytes on the chromatographic behavior as the column changes. The four CSPs showed good complementary recognition ability. The elution sequence was determined in 30 cases out of 36. The success rate to afford baseline separations (R_s ≥ 1.5) was estimated: 29 compounds out of 36 showed baseline enantioseparation on at least one of the four selected CSPs. The combined computational‐chromatographic screening furnished useful collective structure‐chromatographic behavior relationships and a map of the chiral discrimination abilities of the considered CSPs towards the analytes. On this basis, the chromatographic behavior of new analytes on a set of polysaccharide‐based CSPs can be mapped through the qualitative correlation of chromatographic parameters (k, α, R_s) to computed molecular properties of the analytes. Chirality 25:709–718, 2013. © 2013 Wiley Periodicals, Inc.