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In the present study, an accurate, rapid, and simple chiral HPLC-UV method with amylose tris(3-chloro-5-methylphenylcarbamate) as stationary phase was developed and applied for enantiomeric determination of six nonsteroidal anti-inflammatory drugs (NSAIDs) in the commercial pharmaceutical formulations, including (R,S)-ibuprofen, S-ibuprofen, (R,S)-ketoprofen, S-ketoprofen, S-naproxen, and (R,S)-loxoprofen sodium. Experiments on the influence of mobile phase composition, proportion of organic modifier, percentage of acid additives, and column temperature on enantioseparation were conducted to obtain the best separation condition. It was indicated that one mobile phase simply composed of acetonitrile-water (0.1% formic acid, v/v) at the proportion of 50:50 (v/v) with a flow rate of 0.6 ml/min at 22°C could simultaneously provide the excellent enantiomeric resolutions for all selected NSAIDs, which made the enantioseparation process more applicable and operable. The newly developed method was then applied for determination of NSAID enantiomers in pharmaceutical formulations containing racemic mixtures or single stereoisomers. Calibration curve of each enantiomer at the concentration of 5.0-100 ug/ml showed good linearity with the correlation coefficient above 0.9996. Satisfactory recovery (96.54-101.54%), good intra-day precision (RSD 0.52-1.46%), and inter-day precision (RSD 0.13-1.09%) were also obtained. The newly developed method was then applied for determination of NSAID enantiomers in pharmaceutical formulations containing racemic mixtures or single stereoisomers. Quantitative results of the commercial capsules and tablets demonstrated that the difference between the declared and measured values did not exceed 1.52%.

Three phthalide-derived analogues, oxaspiroangelioic acids A–C (1–3), were isolated as minor components of an aqueous extract of the Angelica sinensis root heads (guitou). Oxaspiroangelioic acids A and B were racemates separated into enantiomers by chiral HPLC. Their structures including absolute configurations were determined by spectroscopic data analysis, single crystal X-ray diffraction, exciton chirality method and electronic circular dichroism (ECD) calculation. These compounds share an undescribed carbon skeleton, for which biosynthetic pathways are proposed. Compound 1 and its enantiomers showed almost identical activity inhibiting Tandem of P domains in a weak inwardly rectifying K+ channel 1 (TREK-1).

A new pair of enantiomeric isoprenylated chromone derivatives, (±)-pestaloficiol X [(±)-1], along with a known compound pestaloficiol J (2), were isolated from the plant endophytic fungus Pestalotiopsis sp. The racemic mixture 1 was separated through chiral HPLC. The structures of new compounds (±)-1 were elucidated on the basis of extensive spectroscopic data and their absolute configurations were further configured through computational analysis of their electronic circular dichroism (ECD) spectra. Compound (+)-1 showed significant inhibitory potency against HL-60 and HEP-3B cell lines, with IC50 values of 1.35 ± 0.15 and 3.70 ± 0.33 μM, respectively, while compound (-)-1 showed significant inhibitory potency against HL-60 and HEP-3B cell lines, with IC50 values of 2.39 ± 0.26 and 2.99 ± 0.35 μM, respectively.

Polysaccharide-based chiral stationary phases account for a majority of chiral HPLC separations. Their behavior in normal-phase and reversed-phase modes of separation has been studied extensively. However, much less is known about their behavior in polar-organic mode. In the course of our studies on preparative separation of various cyclic imides, lactams, and acetamides on Chiralcel OD, Chiralcel OJ, Chiralpak AD, and Chiralpak AS stationary phases we sought to determine the void volumes of these columns using commonly used markers, LiNO(3), thiourea, and acetone. We were surprised to notice extensive column- and solvent-dependent deviations from ideal (unretained and unexcluded) behavior. These deviations likely result from multiple types of noncovalent interactions possible for these chiral stationary phases. Therefore, great care should be taken when choosing void volume markers for such separations. Our results indicate that with acetonitrile as a mobile phase, acetone is a suitable void volume marker for all four of the above stationary phases.

Inorganic mesoporous silica gel spheres, which possess sufficient mechanical strength, thermal stability, and mobile phase endurance, are the most important and widely used materials for column packing in high performance liquid chromatography (HPLC). However, amorphous silica gel is generally reported as an inorganic chiral silica gel, and spherical all-inorganic chiral silica gel has not been reportedly used as the chiral stationary phase for HPLC. In this paper, inorganic spherical mesoporous silica gel was used in the method of polymerization-induced colloid aggregation (PICA), with silica sol as the raw material and L-glutamic acid (L-Glu) as the chiral monomer, to obtain mixed spheres of urea-formaldehyde resin and colloidal silica in a chiral environment. After high-temperature calcination (at 550 ℃) to remove the resin, inorganic mesoporous silica gel spheres based on L-Glu were prepared. Elemental analysis revealed that the prepared L-Glu chiral silica gel spheres were calcined completely, indicating that there were no organic constituents. Scanning electron microscopy (SEM) images of the silica gel spheres showed that the surface of the silica gel spheres was not smooth, with a uniform particle size of 3.0-4.5 μm. Transmission electron microscopy (TEM) images showed that the pore size distribution of the synthetic silica gel spheres was uniform due to the accumulation of pores. Nitrogen adsorption tests revealed that the specific surface area of L-Glu chiral silica gel spheres was 117.844 m2/g, the pore volume was 0.411 cm3/g, and the average pore size was 12.312 nm. All the characterizations indicated that the inorganic chiral mesoporous silicon had a regular spherical shape. The silica gel spheres possess frameworks and pore structures, providing a chiral microenvironment that is suitable as a chiral stationary phase for separating racemic compounds by HPLC. Because of the chiral pore structure and frameworks, the enantiomers were retained to different degrees and separation was achieved. The porous structure also increased the contact surface between the racemates and the active sites of the inner wall and improved the separation efficiency. Hydrogen bonding between the chiral stationary phase and the racemates, dipole interactions, and van der Waals forces were also involved in enantiomer resolution. An HPLC column was prepared with L-Glu chiral silica gel as the stationary phase and n-hexane-isopropanol (9∶1, v/v) as the mobile phase. Fifteen racemic compounds were successfully separated on the chiral HPLC column, including seven racemic compounds for baseline separation, at a flow rate of 0.1 mL/min using 254 nm as the detection wavelength at 25 ℃. The separation of 10 benzene position isomers was successfully achieved, and eight of the benzene position isomers reached baseline separation. Experimental results showed that the chiral silica gel spheres possess sufficient mechanical strength and thermal stability, along with good chiral recognition ability and the ability to separate positional isomers. Compared with ordinary silica gel, these chiral silica gel spheres afforded better chiral separation and better separation of benzene position isomers, without further modification. The preparation of this chiral stationary phase also has the advantages of being cheap, convenient, and feasible.

Ketamine is a widely used dissociative drug, whose quantification in plasma and urine can be of pharmacological, toxicological, and clinical interest. Although tandem mass spectrometry allows the reliable determination of ketamine and its metabolites in biological matrices, the structural similarity between norketamine (main active metabolite) and dehydronorketamine (a less relevant metabolite) can represent a critical aspect. These compounds differ exclusively in two hydrogen atoms, but the consequent two‐unit difference in their mass/charge ratio is partially nullified by the isotopic abundance of the chlorine atom present in their structure. This, along with their similar fragmentation pattern, can result in the incorrect identification of the enantiomers of these ketamine metabolites even with triple quadrupole instruments, if shared transitions are monitored after chiral chromatography. The key to prevent norketamine overestimation is therefore observing analyte‐specific MS/MS transitions. Here, we describe in detail how we investigated this issue, during the development of an analytical method for ketamine and norketamine enantiomer determination in plasma.

A new concept for the regioselective synthesis of [3 : 2 : 1] hexakis‐adducts of fullerene C60 was developed. Based on sequential tether‐directed remote functionalizations, chiral [3 : 2] pentakis‐adducts with an incomplete octahedral addition pattern were synthesized via stepwise cyclopropanation of C60 with suitable macrocyclic tri‐ and bifunctional cyclomalonate tethers. The four resulting stereoisomers were isolated using chiral HPLC. The corresponding pairs of enantiomers show mirror image behavior in their CD‐spectra. The pentakis‐adducts served as suitable building blocks for the spatially controlled synthesis of mixed hexakis‐adducts. Implementation of functional group‐bearing monomalonates afforded octahedral [3 : 2 : 1] hexakis‐adducts suitable for the construction of larger molecular and supramolecular fullerene architectures in excellent yield., A new concept for the regioselective synthesis of [3 : 2 : 1] hexakis‐adducts of fullerene C60 is presented. Based on sequential tether‐directed remote functionalizations, chiral [3 : 2] pentakis‐adducts with an incomplete octahedral addition pattern were synthesized and isolated. The pentakis‐adducts served as universal building blocks for the spatially controlled synthesis of octahedral [3 : 2 : 1] hexakis‐adducts suitable for the construction of larger molecular and supramolecular fullerene architectures in excellent yield.

The possibility for separating enantiomers of a number of practically significant 2-aryloxycarboxylic acids was studied by normal- and reversed-phase HPLC on popular chiral stationary phases. The best separation parameters were achieved on the chiral phases with the polysaccharide base Chiralcel OD-H and Chiralpack AD under the normal-phase HPLC conditions. The (S)- and (R)-enantiomers of 2-(1-naphthyloxy)- and 2-(2-iodophenoxy)propionic acids with enantiomeric excess ee >99% were isolated using preparative chiral HPLC.

A couple of enantiomers of 2, 6-diaminotriptycene ( R, R - 1 and S, S - 1 ) are split by chiral HPLC and their absolute configurations are identified by single-crystal X-ray diffraction technology. Using the enantiomers as monomers, a couple of chiral porous polyimides ( R - FTPI and S - FTPI ) are prepared by polycondensation reactions and display good heat stability, high BET surface area and good solubility in organic solvents. Moreover, both of R - FTPI and S - FTPI can be cast into robust, free-standing films suitable for enantioselective separation with symmetrical chiral selectivity.

Treatment of 11,12-bis(1,1'-biphenyl-3-yl or 6-phenylpyridin-2-yl)-substituted 11,​12-​dihydro-indolo[2,​3-​ a ]​carbazole with an oxidizing system of Pd(II)/Ag(I) induced effective double dehydrogenative cyclization to afford the corresponding π-extended azahelicenes. The optical resolutions were readily achieved by a preparative chiral HPLC. It was found the pyridopyrrolo-carbazole-based azahelicene that contains four nitrogen atoms exhibits ca. 6 times larger dissymmetry factors both in circularly dichroism (CD) and circularly polarized luminescence (CPL), | g CD | and | g CPL | values being 1.1 × 10 -2 and 4.4 × 10 -3 , respectively, as compared with the parent indolocarbazole-based azahelicene. Theoretical calculations at the RI-CC2 level were employed to rationalize the observed enhanced chiroptical responses. The (chir)optical properties of the former helicene was further tuned by a protonation leading to remarkable red-shift with a considerable enhancement of the | g CPL | value.

The deboronation of enantiomers of planar-chiral benzyl (3-formamido-1,2-dicarba-closo-dodecaboran-1-yl)acetate gave the individual (RP)- and (SP)-enantiomers (ee > 98%) of a new amino acid containing a nido-carborane fragment, (3-ammonio-7,8-dicarba-nido-undecaboran-7-yl)acetic acid. Chiral HPLC methods for the analysis of enantiomeric purity of this compound was developed.

An HPLC method that separates four Non-Steroidal Anti-Inflammatory Drugs (Ketoprofen, Naproxen, Ibuprofen, and Flurbiprofen) and three of the four pairs of enantiomers in one run is reported. The NSAID samples were prepared with 1 mg/mL of Ketoprofen, Naproxen, Ibuprofen and Flurbiprofen, and 0.5 mg/mL thiourea as a t0 marker in a sample solvent consisting of 1: 1 acetonitrile and 0.2% formic acid. The separation of the enantiomers of the NSAIDs was investigated using a chiral column in two different lengths (5-cm, 10-cm) packed with Amylose tris(3,5-dimethylphenylcarbamate) coated on silica gel and using a tandem column that consists of a biphenyl column connected by a zero dead volume connector to a 5-cm chiral column packed with amylose tris(3,5-dimethylphenylcarbamate) coated on silica gel. Both isocratic and step-gradient methods were investigated, and the results of the different methods were compared to determine the benefits and drawbacks of each approach, with an emphasis on the resolution and analysis time.

We report the synthesis of a quadruple helicene with a rubicene core R1 by a Scholl reaction. Among the 10 stereoisomers including 4 pairs of enantiomers and 2 meso isomers, only 2 pairs of enantiomers and 1 meso isomer have been isolated. The sample structures were unambiguously determined by X-ray crystallography to be (P,P)6-(P,P)5/(M,M)6-(M,M)5-R1-A, which has a propeller-shaped structure, and (M,M)6-(P,P)5/(P,P)6-(M,M)5-R1-B and (M,P)6-(P,M)5-R1-C, which have saddle-shaped structures. The chiral resolutions of R1 were carried out by chiral HPLC, revealing two pairs of chiral stereoisomers (P,P)6-(P,P)5/(P,P)6-(M,M)5, (M,M)6-(P,P)5/(M,M)6-(M,M)5 as well as a meso isomer (M,P)6-(P,M)5, which were further characterized by CD spectroscopy and time-dependent density functional theory (TD-DFT) calculations. Surprisingly, the UV-vis absorption and emission spectra of these resolved stereoisomers and unresolved R1 were almost identical. In addition, the chemical oxidation of R1 led to the formation of radical cations and dications at room temperature.

ortho-Substituted and unsymmetrical 9-phospha-triptycenes were synthesizedviatwo synthetic approaches involving densely functionalizedortho-halogenated triarylmethane or phosphine precursors.ortho-Substituents imposed a considerable steric shielding due to the tricyclic cage-shaped structure with the aryl rings p-systems orthogonal to the phosphorus electron pair. A series of Au(i) and Rh(i) complexes were analysed in the solid state to determine Tolman electronic parameters, cone angles and buried volumes of these unprecedented functionalized phosphines. Quantum chemical calculations of electronic and steric descriptors revealed that these cage-shaped phosphines are electron-poor and that single methyl substituent is enough to provide the largest effect on steric shielding reported so far in triarylphosphines. An unsymmetrically substituted 9-phosphatriptycene was resolved by chiral HPLC, opening the avenue towards stableP-chirogenic triarylphosphines with unlimited configurational stability for new catalyst development in asymmetric transition-metal catalysis.

A series of chiral Au13 nanoclusters were synthesized via the direct reduction of achiral dinuclear Au(I) halide complexes ligated by ortho-xylyl-linked bis-N-heterocyclic carbene (NHC) ligands. A broad range of functional groups are tolerated as wingtip substituents, allowing for the synthesis of a variety of functionalized chiral Au13 nanoclusters. Single crystal X-ray crystallography confirmed the molecular formula to be [Au13(bisNHC)5Cl2]Cl3, with a chiral helical arrangement of the five bidentate NHC ligands around the icosahedral Au13 core. This Au13 nanocluster is highly luminescent, with a quantum yield of 23%. The two enantiomers of the Au13 clusters can be separated by chiral HPLC, and the isolated enantiomers were characterized by circular dichroism spectroscopy. The clusters show remarkable stability, including configurational stability, opening the door to further investigation of the effect of chirality on these clusters.

The presence and fate of antifungal agents in the environment have hardly been investigated. This is despite the increased usage of antifungal agents and higher prevalence of antifungal resistance. Stereochemistry of antifungal agents has been largely overlooked due to lack of analytical methods enabling studies at the enantiomeric level. This paper introduces a new analytical method for combined separation of achiral and chiral antifungal agents and their metabolites with the utilization of chiral chromatography coupled with triple quadrupole tandem mass spectrometry to enable comprehensive profiling of wide-ranging antifungal agents and their metabolites in environmental matrices. The method showed very good linearity and range (r2 > 0.997), method accuracy (61–143%) and precision (3–31%) as well as low (ng L−1) MQLs for most analytes. The method was applied in selected environmental samples. The following analytes were quantified: fluconazole, terbinafine, N-desmethyl-carboxyterbinafine, tebuconazole, epoxiconazole, propiconazole and N-deacetyl ketoconazole. They were predominantly present in the aqueous environment (as opposed to wastewater) with sources linked with animal and plant protection rather than usage in humans. Interestingly, chiral fungicides quantified in river water were enriched with one enantiomer. This might have consequences in terms of their ecological effects which warrants further study.

BackgroundTo explore the release behavior of ketoprofen enantiomers from alginate-metal-complexes. Five mathematical models of drug release kinetics were investigated.ResultsBeads of alginate-metal complexes, loaded with racemic ketoprofen, were prepared by the ionotropic method. Divalent (Ca, Ba, Zn) and trivalent (Fe, Al) metals were used in the preparation of single-metal and mixed-metal alginate complexes. In vitro release experiments were carried out in an aqueous phosphate buffer medium at pH = 7.4. The concentrations of ketoprofen released enantiomers were determined using chiral HPLC technique. The obtained data were used to simulate the release kinetic of ketoprofen enantiomers using various mathematical models. The Korsmeyer-Peppas model was the best fit for Ca, Al, and Fe beads. Moreover, alginate-iron beads tend to release the drug faster than all other cases. In contrast, the drug release for alginate-barium complex was the slowest. The presence of barium in alginate mixed-metal complexes reduced ketoprofen release in the case of Fe and Zn, while it increased the release in the case of Al complex.ConclusionIn all the studied cases, ketoprofen showed very slow release for both enantiomers over a period exceeded 5 h (10 days in some cases). The release rate modification is possible using different multivalent metals, and it is also feasible by using two different metals for congealing either consecutively or simultaneously.

Novel ortho-linked tetraphenol strands with electron-deficient naphthalene (NDI) and perylene (PDI) diimide linkers in the middle formed double-stranded homo-helicates bridged by spiroborate groups in the presence of NaBH4. The reaction of an electron-rich porphyrin-linked tetraphenol strand with the NDI-strand quantitatively afforded the double-stranded hetero-helicate assisted by donor–acceptor interactions between the porphyrin and NDI units with a similar molecular length to each other, while that with the longer PDI strand gave a mixture of the corresponding homo- and hetero-helicates. The two isolated homo- and hetero-helicates were successfully resolved into enantiomers by chiral HPLC.

A study is performed of mechanisms of the retention and separation of enantiomers of a series of chiral oxazolopyrroloquinolones on a stationary phase with grafted macrocyclic antibiotic ristocetin A under the conditions of high-performance liquid chromatography using water–acetonitrile mobile phases. It is found that the dependence of the retention factor on the concentration of CH3CN in the mobile phase has a U-shape. An explanation of this phenomenon is given. The thermodynamics of the oxazolopyrroloquinolone adsorption in different parts of this dependence is studied. It is assumed that the adsorption complex forms through inclusion of the oxazole moiety of the adsorbate molecule in the chiral cavity of the grafted selector. The effect the nature of the substituent on the chiral carbon atom in oxazolopyrroloquinolones on enantioseparation is discussed.

Chiral phosphoric acid (CPA) catalyzed asymmetric kinetic resolution polymerization (AKRP) of 6-methyl-e-caprolactone (6-MeCL) has been developed to synthesize stereogradient polycaprolactones. When using (R)-CPA as the catalyst, (R)-6-MeCL monomers were preferentially consumed, which was determined by chiral HPLC analysis and kinetic experiments. The AKRP process delivered polycaprolactones (PCLs) with high chain-end fidelity, controlled molecular weights and narrow molar mass dispersity. Moreover, the thermal properties, viscoelasticity and degradation characteristics of the resulting PCLs were also investigated.

International audience; Based on a N-arylthiazoline scaffold, 22 structures with a N-Caryl chiral axis were synthesized exhibiting a huge molecular diversity for the four flanking substituents around the pivotal bond. The determination of their corresponding rotational barriers by thermal kineticexperiments or from the analysis of plateau shape chiral HPLC chromatogram allowed to rank these compounds according to their enantiomeric stability : 4 rotamers, 5 isolable atropisomers (i.e. not enough robust to be handled without risk of racemization) and 13 stable atropisomers. The influence of the flanking substituents was investigated showing that a minor structural modification may result in a drastic change on the value of the rotational barrier. All these results offer a set data on structure-rotational barrier relationships very helpful to design molecules exhibiting chiral axis or to optimize the enantiomeric stability of such structure. To complete this study, the racemization pathways were examined thanks to X-Ray analysis and DFT calculations, highlighting the importance of the aromatic ring distortion during the transition state on the energetic cost of the rotation

The synthesis and structural analyses of corannulene-PAH hybrids 1 with a [4] helicene subunit and 2 with a [7] helicene subunit have been reported. The structures of 1 and 2 were confirmed by single-crystal X-ray diffraction. The experimental data in combination with theoretical calculations revealed that the terminal ring of helicene and the π-surface of the corannulene unit of 2 adopt a convex conformation, which is a more stable conformation. Meanwhile, 2 displays a red-shift in fluorescence emission but a shorter fluorescence lifetime, in comparison with 1. The optical resolution of 2 was successfully carried out by chiral HPLC, offering enantiopure P-2 and M-2, which were further characterized by CD and CPL spectroscopy.

Four types of tris-chelate ruthenium complexes bearing acetylacetonato (acac) and tropolonato (trop) ligands were synthesized and optically resolved into Δ and Λ isomers: [Ru(acac)3] (Ru-0), [Ru(acac)2(trop)] (Ru-1), [Ru(acac)(trop)2] (Ru-2), and [Ru(trop)3] (Ru-3). Chiral HPLC chromatograms, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) of the four ruthenium complexes were systematically investigated. As a result, the absolute configurations of the newly prepared enantiomeric complexes Ru-2 and Ru-3 were determined. For the case of Ru-2, its absolute configuration was also confirmed by single crystal X-ray diffraction analysis. The ECD changes upon chemical oxidation were further investigated for the four complexes. An ECD change in enantiomeric Ru-1 was observed upon oxidation, but the oxidized species soon returned to the neutral state within a few minutes. Enantiomers of Ru-3 also showed explicit ECD changes upon oxidation. Further, the lifetime of the oxidized state was the longest among the four investigated complexes, whereas they racemized in solution at room temperature. In contrast, the enantiomers of heteroleptic complexes (Ru-1 and Ru-2) concurrently exhibited ECD changes, relatively long lifetime of the oxidized state, and nil or quite slow racemization behavior. The coexistence of acac and trop ligands was key to making the competing factors compatible in the resultant ruthenium complexes.

An overview of molecular modelling approaches, related to chiral separations on polysaccharide-based and macrocyclic antibiotic chiral selectors, is presented. Both atomistic calculations and empirical fitting procedures are discussed. Atomistic calculations, such as docking and molecular dynamics can be used to model the interactions between enantiomers and the chiral stationary phase. This may help obtaining information about the chiral recognition mechanism. Conversely, in empirical fitting procedures, mathematical models for relevant separation parameters are fitted to experimental observations. The latter use theoretical molecular descriptors, calculated from the molecular structure, which are combined into a model to predict a given response, for example, retention. Such relationships, when used in chiral separations, are often called quantitative structure enantioselective retention relationships (QSERR) and an increased interest in them can be observed in the literature. Different regression models are discussed, such as multiple linear regression and partial least squares.

Starting from methyl cycloheptatrienyl-1-carboxylate, 6-acylation was successfully achieved employing glutaryl chloride in the presence of AlCl3 under controlled reaction conditions to furnish keto carboxylic acid product. After protection of this keto carboxylic acid as tert-butyl ester, reagent-controlled enantioselective reductions delivered configuration-defined methyl-6-hydroxylalkyl cycloheptatriene-1-carboxylates with up to 80% ee. Whereas simple NaBH4 reduction of the keto carboxylic acid and subsequent lactonization afforded a methyl-6-tetrahydropyranonyl cycloheptatriene-1-carboxylate. Resolution using chiral HPLC delivered the product enantiomers with up to >99% ee Finally, ECD analyses enabled structure elucidation. The products are used as key intermediates in enantioselective 6,11-methylene-lipoxin B4 syntheses.

Many inorganic materials can form crystals, but little is known about their enantioselective crystallization. Herein, we report on the enantioselective crystallization of ϵ-Zn(OH)2 (Wulfingite) chiral crystals by using amino acids. Crystals of ϵ-Zn(OH)2 were crystallized from supersaturated sodium hydroxide and zinc nitrate aqueous solutions in the presence of l- or d-arginine. All of the chiral measurements, such as selective chiral adsorption by circular dichroism (CD), chiral chromatography, and polarimetry measurements, clearly show chiral discrimination during the crystallization of ϵ-Zn(OH)2 . In addition, a new method has been developed for identifying chirality in crystals by using electron paramagnetic resonance (EPR). Although the values of chiral induction of the ϵ-Zn(OH)2 crystals obtained are somewhat low, these values are still significant because they demonstrate that enantioselectivity during the crystallization of chiral inorganic crystals with chiral additives can be achieved. The method can be applied to many chiral inorganic systems. Understanding and controlling the crystallization of chiral inorganic crystals is important for gaining knowledge on the interaction of chiral molecules with inorganic surfaces. This knowledge can lead to an understanding of basic scientific questions such as the evolution of homochirality in biomolecules and the development of chiral inorganic crystals for a variety of purposes such as asymmetric catalysis and optical applications.

Triglycerides (TG) not only provide energy for infants but have important physiological functions. Understanding the composition and structure of TG in human milk is conducive to the development of infant formulas. In this study, TG species in human milk from 3 provincial capitals (Zhengzhou, Wuhan, and Harbin) in different regions of China were determined through C18 HPLC electrospray ionization tandem mass spectrometry (MS). The results showed that in human milk from these 3 regions, oleoyl-palmitoyl-linoleoylglycerol (OPL; 16.55, 19.20, and 18.67%, respectively) was more abundant than oleoyl-palmitoyl-oleoylglycerol (OPO; 10.08, 10.22, and 12.03%, respectively). Subsequently, regioisomeric and enantiomeric analysis of main TG in the human milk were performed on silver ion and chiral HPLC atmospheric pressure chemical ionization mass spectrometry (APCI)-MS, respectively. The results showed that rac-OPL (above 85%), rac-OPO (above 85%), rac-palmitoyl-oleoyl-oleoylglycerol (PPO; above 90%), and rac-OLaO (above 70%) were the main regioisomers of OPL, OPO, PPO, and lauroyl-oleoyl-oleoylglycerol (LaOO), respectively. The relative ratios of enantiomer pairs of rac-OPL (rac-OPL1 and rac-OPL2) were about 37 and 63%, respectively.

Abstract Ten neolignans or norlignans (1–10) including eight new compounds were isolated from the whole bodies of Polyphaga plancyi Bolivar. Their structures were identified by spectroscopic data. Compounds 3, 4, 8, and 9 are racemates indicated by chiral HPLC analysis. Chiral separation followed by ECD calculations allowed to clarify the absolute configurations of all the antipodes. All the new compounds were evaluated for their biological properties toward extracellular matrix in rat renal proximal tubular cells, human cancer cells (K562, A549, and Huh7), EV71, ROCK2, JAK3, DDR1, and coagulation. Graphic Abstract

Four enantiomeric forms of natural prostaglandins, ent-PGF2&alpha, ((&minus, )-1), ent-PGE2 ((+)-2) ent-PGF1&alpha, )-3), and ent-PGE1 ((+)-4) have been synthetized in gram scale by Corey synthesis used in the prostaglandin plants of CHINOIN, Budapest. Chiral HPLC methods have been developed to separate the enantiomeric pairs. Enantiomers of natural prostaglandins can be used as analytical standards to verify the enantiopurity of synthetic prostaglandins, or as biomarkers to study oxidation processes in vivo.

Currently, effective control of optical purity by chiral separation of (S) and (R) enantiomers remains a relevant and highlighted task when designing new chiral organic materials in general, especi...

The chiral separation by counter-current chromatography has made great progress in the past three decades. It has become increasingly popular in the field of chiral separation, and many applications have been introduced during the last years. This review mainly focuses on the current topics, applications, and trends in chiral separation by counter-current chromatography. It contains the development of modern counter-current chromatography apparatus, theory of counter-current chromatography, overview of applications of chiral counter-current chromatography enantioseparation, its current situation, and challenges. At last, some conclusions and perspectives also have been discussed in this review.

This manuscript presents the development, validation and application of a multi-residue supercritical fluid chromatography coupled with tandem mass spectrometry method for the analysis of 140 chiral and non-chiral chemicals of emerging concern in environmental samples, with 81 compounds being fully quantitative, 14 semi-quantitative and 45 qualitative, validated according to European Medicine Agency (EMA) guidelines (European Medicines Agency 2019). One unified LC-MS method was used to analyse all analytes, which were split into three injection methods to ensure sufficient peak resolution. The unified method provided an average of 113% accuracy and 4.5% precision across the analyte range. Limits of detection were in the range of 35 pg L−1–0.7 μg L−1, in both river water and wastewater, with an average LOD of 33 ng L−1. The method was combined with solid-phase extraction and applied in environmental samples, showing very good accuracy and precision, as well as excellent chromatographic resolution of a range of chiral enantiomers including beta-blockers, benzodiazepines and antidepressants. The method resulted in quantification of 75% of analytes in at least two matrices, and 56% in the trio of environmental matrices of river water, effluent wastewater and influent wastewater, enabling its use in monitoring compounds of environmental concern, from their sources of origin through to their discharge into the environment. Electronic supplementary material The online version of this article (10.1007/s00216-020-02780-9) contains supplementary material, which is available to authorized users.

Localized partitioning of amorphous enantioenriched aryl benzyl sulfoxides in the solid state can lead to substantial variation in enantiopurities, even for sulfoxides which do not show detectable levels of self-disproportionation of enantiomers (SDE) during chromatography on an achiral stationary phase. The importance of preparation of representative samples of enantioenriched sulfoxides for chiral HPLC to enable reproducible results is clear.

Chiral separations are one of the important analytical tasks, since there are increasing demands for production of enantiomerically pure compounds. The separation and determination of enantiomers find applications in pharmaceutical and food analysis, and it is necessary to pay attention to the development and improvement of chiral analytical methods. High performance liquid chromatography (HPLC) with chiral stationary phase (CSP) based on molecularly imprinted polymers (MIPs) is perspective way. One of the main advantage of these stationary phases is the possibility of predetermining the elution order of enantiomers. The presented work is focused on the methods of preparation and the applications of selective sorption materials (MIPs) in the field of HPLC separation of biologically active substances, amino acids. This review contains comprehensive informations about MIP-amino acid synthesis: compositions of polymerization mixture (monomer, template, cross-linker, porogen), type of polymerization and polymerization conditions, what can affect final efficiency of enantioseparation. The most used porogen was toluene, crosslinker ethylene glycol dimethacrylate (EDMA) and initiator azoisobutyronitrile (AIBN). MIP CSP prepared for derivatized amino acids show better results (higher resolution) than MIP prepared for underivatized amino acids. MIP are very promising material to be used as stationary phase in HPLC, although further developments and new approaches are necessary to fully exploit their potential.

Antimicrobial screening of an in-house library containing both natural products and synthetic compounds identified a bisindole molecule as a selective antibacterial hit. Further evaluation and structural modification afforded a series of dimeric indole derivatives, most of which showed moderate to good antibacterial activity against two Gram-positive strains Staphylococcus aureus and Bacillus subtilis. Chiral HPLC was employed to separate these racemates and the bioactive differences between the enantiomeric pairs were also assessed and discussed. Three dihalogenaged analogues also showed mild growth inhibition against a drug-resistant S. aureus strain.

In the hexahedral hydrocarbon cubane, replacing hydrogen with other atoms at three positions within any one of the internal tetrahedrons can conceptually lead to the formation of a unique class of chiral molecules. In pursuit of this endeavor, we prepared 1,3-dibromo-4-deuteriocubane-N,N-diisopropylcarboxamide, which upon treatment with zincates affords 1,3,5-trisubstituted cubanes via simultaneous two-position substitution reactions. The proposed chiral attributes of this stereogeometric class were confirmed by enantiomeric resolution of a p-bromobenzyl derivative using chiral HPLC.

International audience; Placobranchus ocellatus, regarded as a “solar-powered” sacoglossan mollusk, is well known to produce diverse and complex γ-pyrone polypropionates. Unexpectedly, in this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery of ocellatusones AD, a series of racemic non-γ-pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane (1, 2), a bicyclo[3.3.1]nonane (3) or a mesitylene-substituted dimethylfuran-3(2H)-one core (4). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X-ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 14 after chiral HPLC resolution. An important array of new and diversity-generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co-occurring γ-pyrones (510). Furthermore, the successful biomimetic synthesis of ocellatusone A (1) from its γ-pyrone precursor (5) confirmed the biosynthetic relationship of these two compounds and the proposed rearrangement through an unprecedented acid promoted cascade reaction. Besides, an initially untargeted semisynthetic product, polycyclic lactone 11 with another novel carbocyclic skeleton was proved to be naturally occurring in the mollusk by comparative LC-MS/MS analysis, which provides a strategy to fish a vast number of novel trace components in Nature.

Professor William H. Pirkle (1934-2018) made a profound impact on modern chemistry by inventing and popularizing widely used techniques for the analysis and purification of enantiomers, contributions that paved the way for the subsequent advances in the discovery, development, and manufacture of enantiopure pharmaceuticals, agrochemicals, and specialty chemicals. Pirkle's pioneering 1966 demonstration of the use of chiral solvating agents for the nuclear magnetic resonance determination of enantiopurity led to a lifelong interest in understanding the supramolecular interactions responsible for enantiodifferentiation. Ongoing research into the chromatographic resolution of stereoisomers throughout the 1970s led in 1981 to the very first commercialization of a chiral stationary phase for the high-performance liquid chromatography (HPLC) separation of enantiomers. The availability of this and subsequent "Pirkle columns" had a deep and lasting impact, becoming widely embraced by the chemical sciences research community worldwide and spearheading the wholesale changeover to HPLC as the preferred technique for measuring enantiopurity. Doc Pirkle was a highly creative, independent, and fun-loving collaborator whose circle of friends extends around the globe. His research group at the University of Illinois, often referred to as The Pirkle Zoo, became a refuge for an interesting assembly of characters who flourished under his mentorship and guidance.

The enantiomers of carboline-based cryptates were successfully resolved by chiral HPLC. These complexes show high configurational stability under harsh conditions and their absolute configuration was determined by comparing theoretical and experimental electronic circular dichroism spectra. The enantiopure cryptates exhibit strong circularly polarized luminescence with a maximum dissymmetry factor glum = 0.25 for the f-f transition 5D0→7F1 (λ = 594 nm) under visible light excitation at λex = 400 nm.

We report a one-step enantioselective synthesis of mechanically planar chiral [2]rotaxanes. Previous studies of such molecules have generally involved the separation of enantiomers from racemic mixtures or the preparation and separation of diastereomeric intermediates followed by post-assembly modification to remove other sources of chirality. Here, we demonstrate a simple asymmetric metal-free active template rotaxane synthesis using a primary amine, an activated ester with a chiral leaving group, and an achiral crown ether lacking rotational symmetry. Mechanically planar chiral rotaxanes are obtained directly in up to 50% enantiomeric excess. The rotaxanes were characterized by NMR spectroscopy, high-resolution mass spectrometry, chiral HPLC, single crystal X-ray diffraction, and circular dichroism. Either rotaxane enantiomer could be prepared selectively by incorporating pseudoenantiomeric cinchona alkaloids into the chiral leaving group.

R-Lacosamide (RLC) is a new approved antiepileptic drug for adjunctive use and monotherapy for partial-onset seizures in some countries. RLC use in other epilepsies and diseases is under study. Research is also going on the activities exhibited by the S-enantiomer (SLC). Taking into consideration further perspectives, the development of direct chiral method that can selectively estimate R-isomer in the presence of S-isomer from human plasma is needed. Plasma samples were spiked with RLC, deuterated internal standard, and SLC. Deuterated RLC as the internal standard enabled us to precisely measure the concentration of RLC by minimizing variations associated with the extraction, ionization, and separation. Target compounds were recovered by liquid-liquid extraction from human plasma using methyl tert-butyl ether. The percentage recovery was found to be 68%.The isomers were resolved completely using DIACEL-IC3 column in the reverse phase mode. The retention times of R- and S-isomers were found to be 6.20 ± 0.5 and 8.00 ± 0.5 min, respectively. The proposed method was found to be linear in a concentration range from 1.00 × 102 to 1.50 × 104 ng/mL. Direct chiral HPLC tandem mass spectrometric method that can quantify R-lacosamide in the presence of S-isomer from human plasma without any carry-over and matrix effects was successfully developed. This method is very simple, fast, economic, sensitive, and validated as per EMA guidelines.

The synthesis of conjugated Möbius molecules remains elusive since twisted and macrocyclic structures are low-entropy species sporting their own synthetic challenges. Here we report the synthesis of a Möbius macrocycle in 84% yield via alkyne metathesis of 2,13-bis(propynyl)[5]helicene. MALDI-MS, NMR spectroscopy, and X-ray diffraction indicated a trimeric product of twofold symmetry with

In our continuing search for secondary metabolites from plants, we investigated the chemical constituents of various Okinawan plants. From the stems and leaves of Croton cascarilloides (Euphorbiaceae), a great number of rare diterpenoids: crotofolanes; crotocascarins A-Q, and new diterpenoids; rearranged nor-crotofolanes: crotocascarins α-γ; a rearranged crotofolane: neocrotocascarin; and a new skeletal diterpenoid: isocrotofolane glucoside were isolated. Their structures were mainly elucidated from NMR spectroscopic evidence. In addition, absolute configurations of crotocascarins A, B, K and O, crotocascarin α and neocrotocascarin were determined by X-ray crystallographic analyses, chiral HPLC analyses of 2-methylbutyric acid in their molecules, application of the circular dichroism rule for the α,β-unsaturated γ-lactone ring, and the modified Mosher's method. The absolute structures of crotofolanes were reported for the first time, and a biosynthetic mechanism for the formation of crotocascarin α and neocrotocascarin from crotocascarin B was proposed. Other interesting compounds, namely diosmarioside H: a dimeric ent-kaurane glycoside from the leaves of Diospyros maritima, and melionosides A-C: megastigmane glucosides with a spiro-ring structure from the leaves of Meliosma lepidota ssp. squamulata were also isolated.

Objectives Ketotifen (K) and its active metabolite norketotifen (N) exist as optically active atropisomers. They both have antihistaminic and anti-inflammatory properties but the S-atropisomer of N (SN) causes less sedation than K and RN in rodents. This study investigated whether this could be related to a lower concentration of SN in brain or a lower affinity of SN for rat brain H1 receptors. Methods Ketotifen and norketotifen atropisomers were quantified using a validated chiral HPLC assay. RBE4 and Caco-2 cell monolayers were used in uptake and permeability studies, respectively. Free and total brain-to-plasma (B/P) ratios were determined after injecting racemic K and N into rat tail veins. Affinity for rat brain H1 receptors (KI) was determined using the [3H]mepyramine binding assay. Key findings Uptake and permeation studies indicate no stereoselective transport for K or N. B/P ratios reveal the brain concentration of N is lower than K with no stereoselective transport into brain. Finally, the [3H]mepyramine binding assay shows SN has the lowest affinity for rat brain H1 receptors. Conclusion The lower sedative effect of SN in rodents is probably due to a combination of a lower uptake of N than K into the brain and less affinity of SN for CNS H1 receptors.