Mechanism of chiral asymmetry generation by chiral autocatalysis in the preparation of chiral octahedral cobalt complex

Chiral asymmetry generation, the predominant production of one enantiomer in a non-chiral environment, could occur in the production of the chiral complex cis-[CoBr(NH₃)(en)₂]Br₂ by the reaction of [Co(H₂O)₂{(OH)₂Co(en)₂}₂](SO₄)₂ with ammonium bromide in an aqueous medium. The main kinetic steps in the reaction system have been determined. During the reaction, the product crystallizes at an early stage. When a very small amount of crystalline enantiomer was added to the reaction system at an early stage, the same enantiomer was produced preferentially; in addition, the enantiomeric excess of the product increased with increasing the stirring rate. Thus, it seems that each enantiomer generates chiral crystals that could self-replicate through secondary nucleation when the solution is stirred; these crystals in turn enhance the production of the same enantiomer. With a computer code that simulates such a kinetic mechanism, it is shown that enantiomeric excess observed in the experiments could be reproduced. Chirality 10:343–348, 1998. © 1998 Wiley-Liss, Inc.     

A Validated Normal Phase LC Method for Enantiomeric Separation of Rasagiline Mesylate and Its (S)‐Enantiomer on Cellulose Derivative‐Based Chiral Stationary Phase

A simple, sensitive, and robust normal‐phase isocratic HPLC‐UV method was developed and validated for the enantiomeric separation of rasagiline mesylate and its (S)‐enantiomer. The rasagiline and its (S)‐enantiomer were resolved on a Chiralcel‐OJ‐H (4‐methylbenzoate cellulose coated on silica) column using a mobile phase consisting of n‐hexane:isopropyl alcohol:ethanol:diethyl amine (96:2:2:0.01) at a flow rate of 1.0 ml/min. The column temperature was maintained at 27 °C and elution was monitored at 215 nm. The resolution (R_s) between the enantiomers was found to be more than 2.0. The limit of detection and the limit of quantification of the (S)‐enantiomer were found to be 0.35 and 1.05 µg/ml, respectively. The developed method was validated as per ICH guidelines with respect to linearity, limit of detection and quantification, accuracy, precision, and robustness—and satisfactory results were obtained. The sample solution and mobile phase were found to be stable up to 48 h. The method is useful for routine evaluation of the quality of rasagiline mesylate in bulk drug‐manufacturing units. Chirality 25:324–327, 2013. © 2013 Wiley Periodicals, Inc.     

A validated enantiospecific method for determination and purity assay of clopridogrel

A new and accurate HPLC method using β‐cyclodextrin chemically bonded to spherical silica particles as chiral stationary phase (CSP) was developed and validated for determination of S‐clopidogrel and its impurities R‐enantiomer and S‐acid as a hydrolytic product. The effects of acetonitrile and methanol content in the mobile phase and temperature on the resolution and retention of enantiomers were investigated. A satisfactory resolution of S‐clopidogrel active form and its impurities was achieved on ChiraDex® column (5 μm, 4 × 250 mm) at a flow rate of 1.0 ml/min and 17°C using acetonitrile, methanol and 0.01 M potassium dihydrogen phosphate solution (15:5:80 v/v/v) as mobile phase. The detection wavelength was set at 220 nm. The method was validated in terms of accuracy, precision, linearity, and robustness. The limit of detection for R‐enantiomer and S‐acid were 0.75 and 0.09 μg/ml, respectively, injection volume being 20 μl. Finally, the molecular modeling of the inclusion complexes between the analytes and β‐cyclodextrin was performed to investigate the mechanism of the enantiorecognition and to study the quantitative structure–retention relationships. Chirality, 2009. © 2008 Wiley‐Liss, Inc.     

HPLC‐method for determination of permethrin enantiomers using chiral β‐cyclodextrin‐based stationary phase

The liquid chromatographic separation of permethrin enantiomers on chiral β‐cyclodextrin‐based stationary phase has been investigated. All four enantiomers are obtained by using simple methanol and water mobile phase, under gradient mode. The method was optimized and validated. The relationship between temperature and chromatographic parameters: k′ (capacity factor), α (separation factor) and Rs (resolution factor) was studied. Van't Hoff's curves for each enantiomer were plotted for temperature range 288–318 K. It was noticed that the response factor ratio of permethrin isomers differ and calculated value is found to be 1.66 (cis/trans, for n = 5). This method has been used for determining permethrin enantiomer ratio for a few samples of working standards and one formulation. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

Direct high-performance liquid chromatographic separation of penbutolol enantiomers on a cellulose tris-3,5-dimethylphenyl carbamate chiral stationary phase

Penbutolol is a β-adrenoceptor blocking agent, and it contains the clinically relevant (?)-S-enantiomer. It was reported that the (+)-R-enantiomer of penbutolol is pharmacologically 50 times less active than the (?)-S-isomer in β-sympatholysis and without intrinsic sympathomimetic activity and refractory period in the heart muscle. Furthermore, the (+)-R-enantiomer does possess mutagenic activity. A high-performance liquid chromatographic (HPLC) method is described for direct identification, stereochemical separation, and quantitation of (+)-R-enantiomer in the clinically used (?)-S-isomer. The method involves the use of cellulose tris-3,5-dimethylphenyl carbamate chiral stationary phase coated on silica gel (OD-Chiralcel column). The capacity factors (k′) for the first eluted enantiomer and stereochemical separation factor (α) obtained were 1.32 and 1.98, respectively. The maximum stereochemical resolution factor (R) was 5.05. The method could be applied for optical purity determination of (?)-(S)-penbutolol in pharmaceutical formulation to detect for the presence of the undesirable (+)-R-enantiomer.     

Chiral HPLC determination and stereoselective pharmacokinetics of tetrahydroberberine enantiomers in rats

Tetrahydroberberine (THB), a racemic mixture of (+)‐ and (?)‐enantiomer, is a biologically active ingredient isolated from a traditional Chinese herb Rhizoma corydalis (yanhusuo). A chiral high performance liquid chromatography method has been developed for the determination of THB enantiomers in rat plasma. The enantioseparation was carried out on a Chiral®‐AD column using methanol:ethanol (80:20, v/v) as the mobile phase at the flow rate 0.4 ml/min. The ultraviolet detection was set at 230 nm. The calibration curves were linear over the range of 0.01–2.5 μg/ml for (+)‐THB and 0.01‐5.0 μg/ml for (?)‐THB, respectively. The lower limit of quantification was 0.01 μg/ml for both (+)‐THB and (?)‐THB. The stereoselective pharmacokinetics of THB enantiomers in rats was studied after oral and intravenous administration at a dose of 50 and 10 mg/kg racemic THB (rac‐THB). The mean plasma levels of (?)‐THB were higher at almost all time points than those of (+)‐THB. (?)‐THB also exhibited greater C_max, and AUC_0–∞, smaller CL and V_d, than its antipode. The (?)/(+)‐enantiomer ratio of AUC_0–∞ after oral and intravenous administration were 2.17 and 1.43, respectively. These results indicated substantial stereoselectivity in the pharmacokinetics of THB enantiomers in rats. Chirality, 2012. © 2012 Wiley Periodicals, Inc.     

Simultaneous LC/ESI‐MS Separation Method for the Enantioseparation of Some New Anticonvulsant Drugs

A sensitive and specific method for the simultaneous determination of the enantiomeric purity of 2,6‐dimethylphenoxyacetyl derivatives as trans or cis racemic and enantiomeric forms with 2‐ or 4‐aminocyclohexanol moiety ( 1 , 2 , 3 , 6 ) and their amine analogs ( 8 , 9 ) was developed. The compounds studied are known for their anticonvulsant activity and the most interesting pharmacological results were those for (±)‐trans‐2‐(2,6‐dimethylphenoxy)‐N‐(2‐hydroxycyclohexyl)acetamide ( 1 ) as well as (±)‐trans‐2‐[(2,6‐dimethylphenoxy)ethyl]aminocyclohexanol ( 8 ). The analytical method for determining the enantiomeric purity of the compounds studied is based on direct separation of the analytes using a chiral stationary phase (Chiralpak AS column). The mass spectrometric analysis was done on a coupled liquid chromatograph–mass spectrometer system with an electrospray ionization source (LC/ESI‐MS). For the compounds 1 , 8 , and 9 , the method allows an excellent separation of enantiomers, with a resolution higher than 3.2, and a tailing factor of less than 1.67 with a final enantiomer purity better than 97.5%. Chirality 26:144–149, 2014. © 2014 Wiley Periodicals, Inc.     

Enantioseparation of racecadotril using polysaccharide‐type chiral stationary phases in polar organic mode

Enantioseparation of the antidiarrheal drug, racecadotril, was investigated by liquid chromatography using polysaccharide‐type chiral stationary phases in polar organic mode. The enantiodiscrimininating properties of 4 different chiral columns (Chiralpak AD, Chiralcel OD, Chiralpak AS, Chiralcel OJ) with 5 different solvents (methanol, ethanol, 1‐propanol, 2‐propanol, and acetonitrile) at 5 different temperatures (5–40 °C) were investigated. Apart from Chiralpak AS column the other 3 columns showed significant enantioseparation capabilities. Among the tested mobile phases, alcohol type solvents were superior over acetonitrile, and significant differences in enantioselective performance of the selector were observed depending on the type of alcohol employed. Van't Hoff analysis was used for calculation of thermodynamic parameters which revealed that enantioseparation is mainly enthalpy controlled; however, enthropic control was also observed. Enantiopure standard was used to determine the enantiomer elution order, revealing chiral selector—and mobile‐phase dependent reversal of enantiomer elution order. Using the optimized method (Chiralcel OJ stationary phase, thermostated at 10 °C, 100% methanol, flow rate: 0.6 mL/min) baseline separation of racecadotril enantiomers (resolution = 3.00 ± 0.02) was achieved, with the R‐enantiomer eluting first. The method was validated according to the ICH guidelines, and its application was tested on capsule and granules containing the racemic mixture of the drug.     

Enantioresolution of Chiral Derivatives of Xanthones on (S,S)‐Whelk‐O1 and l‐Phenylglycine Stationary Phases and Chiral Recognition Mechanism by Docking Approach for (S,S)‐Whelk‐O1

The resolution of seven enantiomeric pairs of chiral derivatives of xanthones (CDXs) on (S,S)‐Whelk‐O1 and l ‐phenylglycine chiral stationary phases (CSPs) was systematically investigated using multimodal elution conditions (normal‐phase, polar‐organic, and reversed‐phase). The (S,S)‐Whelk‐O1 CSP, under polar‐organic conditions, demonstrated a very good power of resolution for the CDXs possessing an aromatic moiety linked to the stereogenic center with separation factor and resolution factor ranging from 1.91 to 7.55 and from 6.71 to 24.16, respectively. The chiral recognition mechanisms were also investigated for (S,S)‐Whelk‐O1 CSP by molecular docking technique. Data regarding the CSP–CDX molecular conformations and interactions were retrieved. These results were in accordance with the experimental chromatographic parameters regarding enantioselectivity and enantiomer elution order. The results of the present study fulfilled the initial objectives of enantioselective studies of CDXs and elucidation of intermolecular CSP–CDX interactions. Chirality 25:89–100, 2013. © 2012 Wiley Periodicals, Inc.     

Distribution of enantiomers of volatile organic compounds in selected fruit distillates

The enantiomer ratios of chiral volatile organic compounds in fruit distillates were determined by multidimensional gas chromatography using solid‐phase microextraction (SPME) as a sample treatment procedure. Linalool and its oxides, limonene, α‐terpineol, and nerolidol, were present at the highest concentration levels, while significantly lower amounts of β‐citronellol and lactones were found in the studied samples. However, almost all terpenoids mainly occur as a racemic or near‐racemic mixture; enantiomer distribution of some chiral organic compounds in fruit distillates correlated to a botanical origin. In particular, a significant enantiomeric excess of (R)‐linalool and (S)‐α‐terpineol was found only for pear brandy, and likewise the dominance (R)‐limonene and the second eluted enantiomer of nerolidol for Sorbus domestica and strawberry, respectively. The distribution of γ‐lactones stereoisomers was more nonspecific, with a general excess of the R‐enantiomer.     

Detection of Xeljanz Enantiomers in Diethyl Amine Active Pharmaceutical Ingredients and Tablets

A high‐performance liquid chromatography (HPLC) method was established to detect Xeljanz enantiomers in active pharmaceutical ingredients (APIs) and tablets. The separation was achieved on a Chiralpak IC column using a mobile phase of hexane‐ethanol‐diethylamine (65:35:0.1, v/v). The detection wavelength was 289 nm. The peak areas and the enantiomer concentrations in the range of 0.15–2.25 μg?mL^?1 were in high linearity, with correlation coefficients higher than 0.999. The recoveries were 86.44% at the concentrations of 7.5, 18.75, and 37.5 μg?mL^?1. The limit of detection (LOD) and limit of quantification (LOQ) were 0.042 and 0.14 μg?mL^?1, respectively. This HPLC method is suitable for detecting the enantiomers of Xeljanz in its APIs and tablets. Chirality 27:235–238, 2015. © 2014 Wiley Periodicals, Inc.     

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.     

Retention model for the resolved enantiomers of felodipine on chiral-AGP using micellar mobile phases

A retention model for the chiral separation of an uncharged solute, felodipine, on CHIRAL-AGP, using a micellar mobile phase is proposed. The model assumes the presence of two stereoselective sites and each enantiomer was found to interact with different sites. Addition of a chiral aliphatic alcohol, (+)-(S)-2-octanol, preferentially interacted with the binding site for (?)-(S)-felodipine. The monomeric form of the micellar agent (Tween® 20) competed with the enantiomers for the adsorption sites, and the formation of a 1:1 complex between the enantiomers and the micelles was assumed. The retention of the solutes was effectively controlled by adding small quantities (<1.63 × 10^?3 M) of the nonionic detergent Tween 20 to the mobile phase. Baseline separation was achieved by addition of 1.0 mM n-octylamine to the mobile phase; 8.14 × 10^?4 M Tween 20 in phosphate buffer pH 7.0. The separation factor (α = 1.74) was unaffected by the detergent concentration in the presence of 1.0 mM n-octylamine. © 1995 Wiley-Liss, 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.     

Effects of metalaxyl enantiomers stress on root activity and leaf antioxidant enzyme activities in tobacco seedlings

The objective of this experiment was to study the effects of metalaxyl enantiomers on the activity of roots and antioxidative enzymes in tobacco seedlings. Water culture experiment was conducted to analyze the effects of different concentrations of metalaxyl enantiomers (30 and 10 mg L^?1) on root activity and leaf superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities and malondialdehyde (MDA) content of tobacco seedlings. The results showed that metalaxyl significantly inhibited root activity and significantly improved leaf SOD, POD, and CAT activities and MDA content. A better physiological response in tobacco seedlings was observed at 30 mg L^?1 than at 10 mg L^?1 metalaxyl. The stereoselectivity for different enantiomers had no obvious effect on root activity and the leaf POD activity, but it affected significantly the SOD and CAT activities and MDA content. The SOD activity was promoted more by R‐enantiomer than by S‐enantiomer at 30 mg L^?1 metalaxyl, and the same effect was observed on CAT activity from the beginning to the end of the stress period. The MDA content under the stress by R‐enantiomer was higher than that under the stress by S‐enantiomer at 10 mg L^?1 metalaxyl.     

Allosteric modulation by single enantiomers of a C3-chiral 1,4-benzodiazepine of the gamma aminobutyric acid type A receptor channel expressed in Xenopus oocytes

Xenopus laevis oocytes injected with Poly(A)⁺-RNA isolated from neuronal tissue express membrane proteins peculiar to the origin of mRNA. The translation of gamma aminobutyric acid type A (GABA_A) receptors has been shown by dose/ response behavior of GABA and the reversible blockade of the GABA-induced current by picrotoxin. This current was analyzed quantitatively under two electrode voltage-clamp conditions. This methodology has been applied for the first time to study the functional properties of the receptor as a function of the stereochemistry of the ligands. The (+)-S and (-)-R enantiomers of a water-soluble benzodiazepine derivative, 7-chloro-1,3-dihydro-3-hemisuccinyloxy-5-phenyl-1,4-benzodiazepin-2-one (OXHEM), obtained by preparative high performance liquid chromatographic (HPLC) resolution on chiral stationary phase, act as agonists in the in vitro modulation of the chloride channel. The (+)-S-OXHEM enantiomer was the more active. Chirality 9:286–290, 1997. © 1997 Wiley-Liss, Inc.     

Enantioseparation of Four Organophosphonate Derivatives on N‐(3,5‐Dinitrobenzoyl)‐ l‐leucine–n‐Propylamide Stationary Phase by Molecular Modeling

Four groups of organophosphonate derivatives enantiomers were separated on N‐(3,5‐dinitrobenzoyl)‐S‐leucine chiral stationary phase. The three‐dimensional structures of the complexes between the single enantiotopic chiral compounds and chiral stationary phase have been studied using molecular model and molecular dynamics simulation. Detailed results regarding the conformation, auto‐docking, and thermodynamic estimation are presented. The elution order of the enantiomer could be determined from the energy. The predicted chiral discrimination was obtained by computational results. Chirality 25:101–106, 2013. © 2012 Wiley Periodicals, Inc.     

Direct Enantioseparation of Nitrogen‐Heterocyclic Pesticides on Cellulose‐Based Chiral Column by High‐Performance Liquid Chromatography

The enantiomeric separation of eight pesticides including bitertanol ( 1 ), diclobutrazol ( 2 ), fenbuconazole ( 3 ), triticonazole ( 4 ), imazalil ( 5 ), triapenthenol ( 6 ), ancymidol ( 7 ), and carfentrazone‐ethyl ( 8 ) was achieved, using normal‐phase high‐performance liquid chromatography on two cellulosed‐based chiral columns. The effects of isopropanol composition from 2% to 30% in the mobile phase and column temperature from 5 to 40 °C were investigated. Satisfactory resolutions were obtained for bitertanol ( 1 ), triticonazole ( 4 ), imazalil ( 5 ) with the (+)‐enantiomer eluted first and fenbuconazole ( 3 ) with the (—)‐enantiomer eluted first on Lux Cellulose‐2 and Lux Cellulose‐3. (+)‐Enantiomers of diclobutrazol ( 2 ) and triapenthenol ( 6 ) were first eluted on Lux Cellulose‐2. (—)‐Carfentrazone‐ethyl ( 8 ) were eluted first on Lux Cellulose‐2 and Lux Cellulose‐3 with incomplete separation. Reversed elution orders were obtained for ancymidol (7). (+)‐Ancymidol was first eluted on Lux Cellulose‐2 while on Lux Cellulose‐3 (—)‐ancymidol was first eluted. The results of the elution order at different column temperatures suggested that column temperature did not affect the optical signals of the enantiomers. These results will be helpful to prepare and analyze individual enantiomers of chiral pesticides. Chirality 27:32–38, 2015. © 2014 Wiley Periodicals, Inc.     

Enantiomeric conservation of the male‐produced sex pheromone facilitates monitoring of threatened European hermit beetles (Osmoderma spp.)

Hermit beetles of the genus Osmoderma (Coleoptera: Scarabaeidae: Cetoniinae) are known for their fruity odour, which is released in large amounts by males. Two species of the genus occur in Europe, the eastern Osmoderma barnabita (Motschulsky) and the western Osmoderma eremita (Scopoli). Previous studies on Swedish populations of O. eremita showed that the compound responsible for the characteristic scent, γ‐decalactone, functions as a sex pheromone for the attraction of conspecific females. Male O. eremita only release the (R)‐enantiomer of the lactone, and both sexes are anosmic to the opposite enantiomer. As the distribution areas of the two hermit beetle species partly overlap, it may be expected that they use different enantiomeric compositions of γ‐decalactone as pheromones to promote species discrimination. This paper reports on the identification of the sex pheromone of O. barnabita. Surprisingly, males from a Polish population produce only the (R)‐enantiomer of γ‐decalactone, and conspecific females show equal attraction to the (R)‐enantiomer and a racemic mixture of the compound, indicating that O. barnabita is anosmic to the (S)‐enantiomer, similarly to what was observed for O. eremita. A mtDNA sequence analysis of the cytochrome oxidase subunit I gene of Polish and Swedish beetles confirmed their taxonomical status as O. barnabita and O. eremita, respectively, with an average sequence divergence of 10.5% between beetles from the two studied areas. Although genetic data suggest that these species diverged several million years ago, they still rely on the same enantiomer of γ‐decalactone for mate finding. Thus, the male‐produced pheromone in Osmoderma spp. may be regarded as a territorial signal being exploited by females, rather than a cue for determining species identity. Our data show that the same compound can be used to facilitate monitoring of both beetle species, which are considered indicator species of the species‐rich fauna of saproxylic insects in Europe.     

Resolution,determination of enantiomeric purity and chiral recognition mechanism of new xanthone derivatives on (S,S)‐whelk‐O1 stationary phase

The enantioresolution and determination of the enantiomeric purity of 32 new xanthone derivatives, synthesized in enantiomerically pure form, were investigated on (S ,S )‐Whelk‐O1 chiral stationary phase (CSP). Enantioselectivity and resolution (α and R_S) with values ranging from 1.41–6.25 and from 1.29–17.20, respectively, were achieved. The elution was in polar organic mode with acetonitrile/methanol (50:50 v/v ) as mobile phase and, generally, the (R )‐enantiomer was the first to elute. The enantiomeric excess (ee ) for all synthesized xanthone derivatives was higher than 99%. All the enantiomeric pairs were enantioseparated, even those without an aromatic moiety linked to the stereogenic center. Computational studies for molecular docking were carried out to perform a qualitative analysis of the enantioresolution and to explore the chiral recognition mechanisms. The in silico results were consistent with the chromatographic parameters and elution orders. The interactions between the CSP and the xanthone derivatives involved in the chromatographic enantioseparation were elucidated.