Enantioselective resolution of 4‐chloromandelic acid by liquid–liquid extraction using 2‐chloro‐N‐carbobenzyloxy‐L‐amino acid

A liquid–liquid extraction resolution of 4‐chloro‐mandelic acid (4‐ClMA) was studied by using 2‐chloro‐N‐carbobenzyloxy‐L‐amino acid (2‐Cl‐Z‐AA) as a chiral extractant. Important factors affecting the extraction efficiency were investigated, including the type of chiral extractant, pH value of aqueous phase, initial concentration of chiral extractant in organic phase, initial concentration of 4‐ClMA in aqueous phase, and resolution temperature. It was observed that the concentration of (R)‐4‐ClMA was much higher than that of (S)‐4‐ClMA in organic phase due to a higher stability of the complex formed between (R)‐4‐ClMA and 2‐Cl‐Z‐AA. A separation factor (α) of 3.05 was obtained at 0.02 mol/L 2‐Cl‐Z‐Valine dissolved in dichloromethane, pH of 2.0, concentration of 4‐ClMA of 0.11 mmol/Land T of 296.7K.     

Studies on Enantioselective Liquid–Liquid Extraction of Amino‐(4‐nitro‐phenyl)‐acetic Acid Enantiomers: Modeling and Optimization

BINAP‐metal complexes were prepared as extractant for enantioselective liquid–liquid extraction (ELLE) of amino‐(4‐nitro‐phenyl)‐acetic acid (NPA) enantiomers. The influence of process variables, including types of organic solvents and metal precursor, concentration of ligand, pH, and temperature on the efficiency of the extraction, were investigated experimentally. An interfacial reaction model was established for insightful understanding of the chiral extraction process. Important parameters required for the model were determined. The experimental data were compared with model predictions to verify the model prediction, It was found that the interfacial reaction model predicted the experimental results accurately. By modeling and experiment, an optimal extraction condition with pH of 7 and host (extractant) concentration of 1 mmol/L was obtained and high enantioselectivity (α_op) of 3.86 and performance factor (pf) of 0.1949 were achieved. Chirality 26:79–87, 2014. © 2013 Wiley Periodicals, Inc.     

Enantioselective liquid‐liquid extraction of DL‐mandelic acid using chiral diphosphine ligands as extractants

In order to expand the application range of chiral diphosphine ligands, (S)‐BINAP, (S)‐SEGPHOS, and (S)‐MeO‐BIPHEP were employed as extractants to recognize DL‐mandelic acid. The results indicated that (S)‐SEGPHOS‐Cu exhibited considerable ability to recognize DL‐mandelic acid with operational enantioselectivity (α) of 2.677. The process of extraction of DL‐mandelic acid using (S)‐SEGPHOS‐Cu as extractant was systematically investigated. Performance factor (pf) was adopted to comprehensively evaluate the extraction. After optimization by response surface methodology (RSM), the optimal extraction condition is temperature of 5.5°C, (S)‐SEGPHOS‐Cu concentration of 3.0 mmol/L, and pH of 8.0. And the predicted and experimental maximum values of pf were 0.26374 and 0.26839, respectively.     

Experimental and Model Studies on Continuous Separation of 2‐Phenylpropionic Acid Enantiomers by Enantioselective Liquid–Liquid Extraction in Centrifugal Contactor Separators

Multistage enantioselective liquid–liquid extraction (ELLE) of 2‐phenylpropionic acid (2‐PPA) enantiomers using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as extractant was studied experimentally in a counter‐current cascade of centrifugal contactor separators (CCSs). Performance of the process was evaluated by purity (enantiomeric excess, ee) and yield (Y). A multistage equilibrium model was established on the basis of single‐stage model for chiral extraction of 2‐PPA enantiomers and the law of mass conservation. A series of experiments on the extract phase/washing phase ratio (W/O ratio), extractant concentration, the pH value of aqueous phase, and the number of stages was conducted to verify the multistage equilibrium model. It was found that model predictions were in good agreement with the experimental results. The model was applied to predict and optimize the symmetrical separation of 2‐PPA enantiomers. The optimal conditions for symmetric separation involves a W/O ratio of 0.6, pH of 2.5, and HP‐β‐CD concentration of 0.1 mol L^?1 at a temperature of 278 K, where ee_eq (equal enantiomeric excess) can reach up to 37% and Y_eq (equal yield) to 69%. By simulation and optimization, the minimum number of stages was evaluated at 98 and 106 for ee_eq > 95% and ee_eq > 97%. Chirality 28:235–244, 2016. © 2016 Wiley Periodicals, Inc. Research highlights are as follows:

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Enantioseparation of Racemic Flurbiprofen by Aqueous Two‐Phase Extraction With Binary Chiral Selectors of L‐dioctyl Tartrate and L‐tryptophan

A novel method for chiral separation of flurbiprofen enantiomers was developed using aqueous two‐phase extraction (ATPE) coupled with biphasic recognition chiral extraction (BRCE). An aqueous two‐phase system (ATPS) was used as an extracting solvent which was composed of ethanol (35.0% w/w) and ammonium sulfate (18.0% w/w). The chiral selectors in ATPS for BRCE consideration were L‐dioctyl tartrate and L‐tryptophan, which were screened from amino acids, β‐cyclodextrin derivatives, and L‐tartrate esters. Factors such as the amounts of L‐dioctyl tartrate and L‐tryptophan, pH, flurbiprofen concentration, and the operation temperature were investigated in terms of chiral separation of flurbiprofen enantiomers. The optimum conditions were as follows: L‐dioctyl tartrate, 80 mg; L‐tryptophan, 40 mg; pH, 4.0; flurbiprofen concentration, 0.10 mmol/L; and temperature, 25 °C. The maximum separation factor α for flurbiprofen enantiomers could reach 2.34. The mechanism of chiral separation of flurbiprofen enantiomers is discussed and studied. The results showed that synergistic extraction has been established by L‐dioctyl tartrate and L‐tryptophan, which enantioselectively recognized R‐ and S‐enantiomers in top and bottom phases, respectively. Compared to conventional liquid–liquid extraction, ATPE coupled with BRCE possessed higher separation efficiency and enantioselectivity without the use of any other organic solvents. The proposed method is a potential and powerful alternative to conventional extraction for separation of various enantiomers. Chirality 27:650–657, 2015. © 2015 Wiley Periodicals, Inc.     

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.     

Preparative Enantioseparation of β‐Substituted‐2‐Phenylpropionic Acids by Countercurrent Chromatography With Substituted β‐Cyclodextrin as Chiral Selectors

Preparative enantioseparation of four β‐substituted‐2‐phenylpropionic acids was performed by countercurrent chromatography with substituted β‐cyclodextrin as chiral selectors. The two‐phase solvent system was composed of n‐hexane‐ethyl acetate‐0.10 mol L‐1 of phosphate buffer solution at pH 2.67 containing 0.10 mol L^‐1 of hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) or sulfobutylether‐β‐cyclodextrin (SBE‐β‐CD). The influence factors, including the type of substituted β‐cyclodextrin, composition of organic phase, concentration of chiral selector, pH value of the aqueous phase, and equilibrium temperature were optimized by enantioselective liquid–liquid extraction. Under the optimum separation conditions, 100 mg of 2‐phenylbutyric acid, 100 mg of tropic acid, and 50 mg of 2,3‐diphenylpropionic acid were successfully enantioseparated by high‐speed countercurrent chromatography, and the recovery of the (±)‐enantiomers was in the range of 90–91% for (±)‐2‐phenylbutyric acid, 91–92% for (±)‐tropic acid, 85–87% for (±)‐2,3‐diphenylpropionic acid with purity of over 97%, 96%, and 98%, respectively. The formation of 1:1 stoichiometric inclusion complex of β‐substituted‐2‐phenylpropionic acids with HP‐β‐CD was determined by UV spectrophotometry and the inclusion constants were calculated by a modified Benesi‐Hildebrand equation. The results showed that different enantioselectivities among different racemates were mainly caused by different enantiorecognition between each enantiomer and HP‐β‐CD, while it might be partially caused by different inclusion capacity between racemic solutes and HP‐β‐CD. Chirality 27:795–801, 2015. © 2015 Wiley Periodicals, Inc.     

Chromatographic profiles of tryptophan and kynurenine enantiomers derivatized with (S)‐4‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐7‐(N,N‐dimethylaminosulfonyl)‐2,1,3‐benzoxadiazole using LC–MS/MS on a triazole‐bonded column

d ‐ and l ‐Tryptophan (Trp) and d ‐ and l ‐kynurenine (KYN) were derivatized with a chiral reagent, (S )‐4‐(3‐isothiocyanatopyrrolidin‐1‐yl)‐7‐(N,N‐dimethylaminosulfonyl)‐2,1,3‐benzoxadiazole (DBD‐PyNCS), and were separated enantiomerically by high‐performance liquid chromatography (HPLC) equipped with a triazole‐bonded column (Cosmosil HILIC) using tandem mass spectrometric (MS/MS) detection. Effects of column temperature, salt (HCO₂NH₄) concentration, and pH of the mobile phase in the enantiomeric separation, followed by MS detection of (S )‐DBD‐PyNCS‐d ,l ‐Trp and ‐d ,l ‐KYN, were investigated. The mobile phase consisting of CH₃CN/10 mM ammonium formate in H₂O (pH 5.0) (90/10) with a column temperature of 50–60 °C gave satisfactory resolution (R s) and mass‐spectrometric detection. The enantiomeric separation of d ,l ‐Trp and d ,l ‐KYN produced R s values of 2.22 and 2.13, and separation factors (α) of 1.08 and 1.08, for the Trp and KYN enantiomers, respectively. The proposed LC–MS/MS method provided excellent detection sensitivity of both enantiomers of Trp and KYN (5.1–19 nM).     

Fractional Reactive Extraction for Symmetrical Separation of 4‐Nitro‐D,L‐Phenylalanine in Centrifugal Contactor Separators: Experiments and Modeling

The enantioselective liquid–liquid extraction of 4‐nitro‐D,L‐phenylalanine (D,L‐Nphy) using PdCl₂{(s)‐BINAP} as extractant in dichloroethane was studied experimentally in a countercurrent cascade of 10 centrifugal contactor separators (CCSs) at 5°C, involving flow ratio, extractant concentration, and Cl^? concentration. The steady‐state enantiomeric excess (ee) in both stream exits was 90.86% at a 93.29% yield. The predicted value was modeled using an equilibrium stage approach. The correlation between model and experiment was satisfactory. The model was applied to optimize the production of both enantiomers in >97% ee and >99% ee. 14 stages and 16 stages are required for 97% ee and 99% ee for both enantiomers, respectively. Chirality 27:75–81, 2015. © 2014 Wiley Periodicals, Inc.     

Enantioselective synthesis and antioxidant activity of 3‐(3,4‐dihydroxyphenyl)‐glyceric acid—Basic monomeric moiety of a biologically active polyether from Symphytum asperum and S. caucasicum

The racemic and enantioselective synthesis of a novel glyceric acid derivative, namely, 2,3‐dihydroxy‐3‐(3,4‐dihydroxyphenyl)‐propionic acid as well as the antioxidant activities is described. The virtually pure enantiomers, (+)‐(2R,3S)‐2,3‐dihydroxy‐3‐(3,4‐dihydroxyphenyl)‐propionic acid and (?)‐(2S,3R)‐2,3‐dihydroxy‐3‐(3,4‐dihydroxyphenyl)‐propionic acid were synthesized for the first time via Sharpless asymmetric dihydroxylation of trans‐caffeic acid derivatives using the enantiocomplementary catalysts, (DHQD)₂‐PHAL and (DHQ)₂‐PHAL. The determination of enantiomeric purity of the novel chiral glyceric acid derivatives was performed by high‐performance liquid chromatographic techniques on the stage of their alkylated precursors. The novel glyceric acid derivatives show strong antioxidant activity against hypochlorite and N,N‐diphenyl‐N‐picryl‐hydrazyl free radical. Their antioxidant activity is about 40‐fold higher than that of the corresponding natural polyether and three‐fold higher of trans‐caffeic acid itself. Chirality, 2010. © 2010 Wiley‐Liss, Inc.     

Optical resolution and mechanism using enantioselective cellulose,sodium alginate and hydroxypropyl‐β‐cyclodextrin membranes

Chiral solid membranes of cellulose, sodium alginate, and hydroxypropyl‐β‐cyclodextrin were prepared for chiral dialysis separations. After optimizing the membrane material concentrations, the membrane preparation conditions and the feed concentrations, enantiomeric excesses of 89.1%, 42.6%, and 59.1% were obtained for mandelic acid on the cellulose membrane, p ‐hydroxy phenylglycine on the sodium alginate membrane, and p ‐hydroxy phenylglycine on the hydroxypropyl‐β‐cyclodextrin membrane, respectively. To study the optical resolution mechanism, chiral discrimination by membrane adsorption, solid phase extraction, membrane chromatography, high‐pressure liquid chromatography ultrafiltration were performed. All of the experimental results showed that the first adsorbed enantiomer was not the enantiomer that first permeated the membrane. The crystal structures of mandelic acid and p ‐hydroxy phenylglycine are the racematic compounds. We suggest that the chiral separation mechanism of the solid membrane is “adsorption – association – diffusion,” which is able to explain the optical resolution of the enantioselective membrane. This is also the first report in which solid membranes of sodium alginate and hydroxypropyl‐β‐cyclodextrin were used in the chiral separation of p ‐hydroxy phenylglycine.     

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.     

Scale‐up and intensification of (S)‐1‐(2‐chlorophenyl)ethanol bioproduction: Economic evaluation of whole cell‐catalyzed reduction of o‐Chloroacetophenone

Escherichia coli cells co‐expressing genes coding for Candida tenuis xylose reductase and Candida boidinii formate dehydrogenase were used for the bioreduction of o‐chloroacetophenone with in situ coenzyme recycling. The product, (S)‐1‐(2‐chlorophenyl)ethanol, is a key chiral intermediate in the synthesis of polo‐like kinase 1 inhibitors, a new class of chemotherapeutic drugs. Production of the alcohol in multi‐gram scale requires intensification and scale‐up of the biocatalyst production, biotransformation, and downstream processing. Cell cultivation in a 6.9‐L bioreactor led to a more than tenfold increase in cell concentration compared to shaken flask cultivation. The resultant cells were used in conversions of 300 mM substrate to (S)‐1‐(2‐chlorophenyl)ethanol (e.e. >99.9%) in high yield (96%). Results obtained in a reaction volume of 500 mL were identical to biotransformations carried out in 1 mL (analytical) and 15 mL (preparative) scale. Optimization of product isolation based on hexane extraction yielded 86% isolated product. Biotransformation and extraction were accomplished in a stirred tank reactor equipped with pH and temperature control. The developed process lowered production costs by 80% and enabled (S)‐1‐(2‐chlorophenyl)ethanol production within previously defined economic boundaries. A simple and efficient way to synthesize (S)‐1‐(2‐chlorophenyl)ethanol in an isolated amount of 20 g product per reaction batch was demonstrated. Biotechnol. Bioeng. 2013; 110: 2311–2315. © 2013 Wiley Periodicals, Inc.     

Enantioseparation of flurbiprofen enantiomers using chiral ionic liquids by liquid‐liquid extraction

Flurbiprofen is a kind of nonsteroidal anti‐inflammatory drug, which has been widely used in clinic for treatment of rheumatoid arthritis and osteoarthritis. It has been reported that S‐flurbiprofen shows good performance on clinic anti‐inflammatory treatment, while R‐enantiomer almost has no pharmacological activities. It has important practical values to obtain optically pure S‐flurbiprofen. In this work, chiral ionic liquids, which have good structural designability and chiral recognize ability, were selected as the extraction selector by the assistance of quantum chemistry calculations. The distribution behaviors of flurbiprofen enantiomers were investigated in the extraction system, which was composed of organic solvent and aqueous phase containing chiral ionic liquid. The results show that maximum enantioselectivity up to 1.20 was attained at pH 2.0, 25°C using 1,2‐dichloroethane as organic solvent, 1‐butyl‐3‐methylimidazole L‐tryptophan ([Bmim][L‐trp]) as chiral selector. The racemic flurbiprofen initial concentration was 0.2 mmol L^?1, and [Bmim][L‐trp] concentration was 0.02 mol L^?1. Furthermore, the recycle of chiral ionic liquids has been achieved by reverse extraction process of the aqueous phase with chiral selector, which is significant for industrial application of chiral ionic liquids and scale‐up of the extraction process.     

Green synthesis of enantiopure (S)‐1‐(benzofuran‐2‐yl)ethanol by whole‐cell biocatalyst

Optically active aromatic alcohols are valuable chiral building blocks of many natural products and chiral drugs. Lactobacillus paracasei BD87E6, which was isolated from a cereal‐based fermented beverage, was shown as a biocatalyst for the bioreduction of 1‐(benzofuran‐2‐yl) ethanone to (S)‐1‐(benzofuran‐2‐yl) ethanol with highly stereoselectivity. The bioreduction conditions were optimized using L. paracasei BD87E6 to obtain high enantiomeric excess (ee) and conversion. After optimization of the bioreduction conditions, it was shown that the bioreduction of 1‐(benzofuran‐2‐yl)ethanone was performed in mild reaction conditions. The asymmetric bioreduction of the 1‐(benzofuran‐2‐yl)ethanone had reached 92% yield with ee of higher than 99.9% at 6.73 g of substrate. Our study gave the first example for enantiopure production of (S)‐1‐(benzofuran‐2‐yl)ethanol by a biological green method. This process is also scalable and has potential in application. In this study, a basic and novel whole‐cell mediated biocatalytic method was performed for the enantiopure production of (S)‐1‐(benzofuran‐2‐yl)ethanol in the aqueous medium, which empowered the synthesis of a precious chiral intermediary process to be converted into a sophisticated molecule for drug production.     

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.     

Preparation and enantioseparation of a mixed selector chiral stationary phase derived from benzoylated tartaric acid and 1,2‐diphenylethylenediamine

L ‐Dibenzoyl tartaric acid was mono‐esterified with benzyl alcohol, and then chlorinated with SOCl₂ to give (2S,3S)‐1‐(benzyloxy)‐4‐chloro‐1,4‐dioxobutane‐2,3‐diyl dibenzoate (Selector 1 ). (1R,2R)‐1,2‐Diphenylethylenediamine was mono‐functionalized with phenyl isocyanate and phenylene diisocyanate in sequence to give (1R,2R)‐1,2‐diphenyl‐2‐(3‐phenylureido)ethyl 4‐ isocyanatophenylurea (Selector 2 ). Two brush‐type chiral stationary phases (CSPs) of single selector were prepared by separately immobilizing selectors 1 and 2 on aminated silica gel. Selectors 1 and 2 were simultaneously immobilized on aminated silica gel to give a mixed selector CSP. The enantioseparation ability of these CSPs was studied. The CSP of selector 1 has strongest separation ability, while the enantioseparation ability of the mixed selector CSP is relatively lower. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

Selector Screening for Enantioseparation of dl‐α‐Methyl Phenylglycine Amide by Liquid–Liquid Extraction

Enantioseparation through liquid extraction technology is an emerging field, e.g., enantioseparations of amino acids (and derivatives thereof), amino alcohols, amines, and carboxylic acids have been reported. Often, when a new selector is developed, the versatility of substrate scope is investigated. From an industrial point of view, the problem is typically approached the other way around, and for a target racemate, a selector needs to be found in order to accomplish the desired enantioseparation. This study presents such a screening approach for the separation of the enantiomers of dl ‐α‐methyl phenylglycine amide (dl ‐α‐MPGA), a model amide racemate with high industrial relevance. Chiral selectors that were reported for other classes of racemates were investigated, i.e., several macrocyclic selectors and Pd‐BINAP complexes. It appeared very challenging to obtain both high extraction yields and good enantioselectivity for most selectors, but Pd‐BINAP‐based selectors performed well, with enantioselectivities up to 7.4 with an extraction yield of the desired enantiomer of 95.8%. These high enantioselectivities were obtained using dichloromethane as solvent. Using less volatile chlorobenzene or 1‐chloropentane, reasonable selectivities of up to 1.7 were measured, making these the best alternative solvents for dichloromethane. Chirality 27:123–130, 2015. © 2014 Wiley Periodicals, Inc.     

Enantioselective Degradation of (2RS, 3RS)‐Paclobutrazol in Rat Liver Microsomes

Paclobutrazol, with two stereogenic centers, but gives only (2R, 3R) and (2S, 3S)‐enantiomers because of steric‐hindrance effects, is an important plant growth regulator in agriculture and horticulture. Enantioselective degradation of paclobutrazol was investigated in rat liver microsomes in vitro. The degradation kinetics and the enantiomer fraction were determined using a Lux Cellulose‐1 chiral column on a reverse‐phase liquid chromatography–tandem mass spectrometry system. The t_1/2 of (2R, 3R)‐paclobutrazol is 18.60 min, while the t_1/2 of (2S, 3S)‐paclobutrazol is 10.93 min. Such consequences clearly indicated that the degradation of paclobutrazol in rat liver microsomes was stereoselective and the degradation rate of (2S, 3S)‐paclobutrazol was much faster than (2R, 3R)‐paclobutrazol. In addition, significant differences between the two enantiomers were also observed in enzyme kinetic parameters. The V_max of (2S, 3S)‐paclobutrazol was more than 2‐fold of (2R, 3R)‐paclobutrazol and the Cl_int of (2S, 3S)‐paclobutrazol was higher than that of (2R, 3R)‐paclobutrazol after incubation in rat liver microsomes. These results may have potential implications for better environmental and ecological risk assessment for paclobutrazol. Chirality 27:344–348, 2015. © 2015 Wiley Periodicals, Inc.     

Estimation of Enantiomeric Impurity in Piperidin‐3‐Amine by Chiral HPLC With Precolumn Derivatization

A simple, precise, accurate, robust chiral high‐performance liquid chromatographic (chiral HPLC) method was developed for estimation of (S)‐piperidin‐3‐amine (S‐isomer) in (R)‐piperidin‐3‐amine dihydrochloride (R‐AMP). As AMP is a high‐melting solid and nonchromophoric compound, development of a suitable chiral method is a challenging task. The proposed chiral HPLC‐UV method involves a precolumn derivatization technique with para toluene sulphonyl chloride (PTSC) in the presence of a base to introduce chromophore into analytes. It utilizes chiralpak AD‐H column with a simple mobile phase of 0.1% diethyl amine in ethanol with a 0.5 mL/min flow rate. Analytes were monitored by using a UV detector at 228 nm. The resolution between the two enantiomers was more than 4.0. The developed method was validated as per current International Conference on Harmonization (ICH) guidelines. Chirality 26:775–779, 2014. © 2014 Wiley Periodicals, Inc.