Differentiation Of Enantiomers Research Articles

Discovery and bioinspired total syntheses of unprecedented sesquiterpenoid dimers unveiled bifurcating [4 + 2] cycloaddition and target differentiation of enantiomers.

[4 + 2] cycloaddition has led to diverse polycyclic chiral architectures, serving as novel sources for organic synthesis and biological exploration. Here, an unprecedented class of cadinane sesquiterpene [4 + 2] dimers, henryinins A-E (1-5), with a unique 6/6/6/6/6-fused pentacyclic system, were isolated from Schisandra henryi. The divergent total syntheses of compounds 1-5 and their enantiomers (6-10) were concisely accomplished in eight linear steps using a protection-free approach. Mechanistic studies illustrated the origin of selectivity in the key [4 + 2] cycloaddition as well as the inhibition of reaction pathway bifurcation via desymmetrization. The chemical proteomics results showed that a pair of enantiomers shared common targets (PRDX5 C100 and BLMH C73) and had unique targets (USP45 C588 for 4 and COG7 C419 for 9). This work provides experimental evidence for the discovery of unprecedented cadinane dimers from selective Diels-Alder reaction and a powerful strategy to explore the biological properties of natural products.

Differentiation and identification of enantiomers by nuclear magnetic resonance spectroscopy with support of quantum mechanical computations.

We report nuclear magnetic resonance studies of two chiral building blocks of solifenacin, phenyltetrahydroisoquinoline and quinuclidinol, in which chiral solvating agents, Mosher's acid, and Pirkle's alcohol were used for spectral discrimination between enantiomers of solifenacin constituents. Based on the constraints following from measurements of the nuclear Overhauser effect, structures of phenyltetrahydroisoquinoline and Pirkle's alcohol solvates were found. Next, shifts of nuclear magnetic resonance signals of phenyltetrahydroisoquinoline due to the application of Pirkle's alcohol were computed using density functional theory methods. The computed carbon-13 shifts reproduce those determined experimentally, allowing us to attribute the absolute configuration to phenyltetrahydroisoquinoline enantiomers without the need for the use of empirical rules.

The Phenomenon of Self-Induced Diastereomeric Anisochrony and Its Implications in NMR Spectroscopy.

Nuclear magnetic resonance (NMR) spectroscopy is an analytical technique largely applied in the analysis of discrimination processes involving enantiomeric substrates and chiral agents, which can interact with the analyte either via covalent bonding or via formation of diastereomeric solvates. However, enantiodiscrimination has been observed, in some cases, even in the absence of any additional chiral selector. The reasons behind this phenomenon must be found in the capability of some chiral substrates to interact with themselves by forming diastereomeric solvates in solution that can generate nonequivalences in the NMR spectra of enantiomerically enriched mixtures. As a result, differentiation of enantiomers is observed, thus allowing the quantification of the enantiomeric composition of the mixture under investigation. The tendency of certain substrates to self-aggregate and to generate diastereomeric adducts in solution can be defined as Self-Induced Diastereomeric Anisochrony (SIDA), but other acronyms have been used to refer to this phenomenon. In the present work, an overview of SIDA processes investigated via NMR spectroscopy will be provided, with a particular emphasis on the nature of the substrates involved, on the interaction mechanisms at the basis of the phenomenon, and on theoretical treatments proposed in the literature to explain them.

Assigning the Absolute Configuration of Inositol Poly- and Pyrophosphates by NMR Using a Single Chiral Solvating Agent.

Inositol phosphates constitute a family of highly charged messenger molecules that play diverse roles in cellular processes. The various phosphorylation patterns they exhibit give rise to a vast array of different compounds. To fully comprehend the biological interconnections, the precise molecular identification of each compound is crucial. Since the myo-inositol scaffold possesses an internal mirror plane, enantiomeric pairs can be formed. Most commonly employed methods for analyzing InsPs have been geared towards resolving regioisomers, but they have not been capable of resolving enantiomers. In this study, we present a general approach for enantiomer assignment using NMR measurements. To achieve this goal, we used 31P-NMR in the presence of L-arginine amide as a chiral solvating agent, which enables the differentiation of enantiomers. Using chemically synthesized standard compounds allows for an unambiguous assignment of the enantiomers. This method was applied to highly phosphorylated inositol pyrophosphates, as well as to lowly phosphorylated inositol phosphates and bisphosphonate analogs. Our method will facilitate the assignment of biologically relevant isomers when isolating naturally occurring compounds from biological specimens.

Dynamic Covalent Reactions and Chirality Sensing with Diphenylethene Derived Hemiaminals.

The differentiation of enantiomers is of significance in synthetic chemistry and pharmaceutical chemistry. Herein, we report a facile method for chirality sensing of monoalcohols, a challenging target due to the poor reactivity, by combining dynamic covalent chemistry with helical chirality. Four diphenylethene (DPE) derived cyclic hemiaminals were constructed, and the incorporation of a broad range of alcohols and thiols with high efficiency was achieved. The reversibility was further verified by dynamic component exchange. The helical chirality of the DPE motif was induced through chirality transfer by the central chirality of the analytes, resulting in circular dichroism responses. The chirality differentiation of seven chiral secondary alcohols including both alkyl and aryl alcohols was realized, further allowing the quantification of enantiomeric excess with high accuracy. The results described should lay a foundation for future endeavors in chemical sensing, asymmetric synthesis, and chiroptical materials.

Light-Controlled Lyotropic Liquid Crystallinity of Polyaspartates Exploited as Photo-Switchable Alignment Medium

Two polyaspartates bearing ortho-fluorinated azobenzenes (pFAB) as photo-responsive groups in the side chain were synthesized: PpFABLA (1) and co-polyaspartate PpFABLA-co-PBLA [11, 75%(n/n) PpFABLA content]. As a consequence of the E/Z-isomerization of the side chain, PpFABLA (1) undergoes a visible-light-induced reversible coil-helix transition in solution: Green light (525 nm) affords the coil, and violet light (400 nm) affords the helix. pFAB significantly increases the thermal stability of the Z-isomer at 20 °C (t1/2 = 66 d for the Z-isomer) and effectively counters the favored back formation of the helix. At 20%(w/w) polymer concentration, the helical polymer forms a lyotropic liquid crystal (LLC) that further orients unidirectionally inside a magnetic field, while the coil polymer results in an isotropic solution. The high viscosity of the polymer solution stabilizes the coexistence of liquid crystalline and isotropic domains, which were obtained with spatial control by partial light irradiation. When used as an alignment medium, PpFABLA (1) enables (i) the measurement of dipolar couplings without the need for a separate isotropic reference and (ii) the differentiation of enantiomers. PpFABLA-co-PBLA (11) preserves the helical structure, by intention, independently of the E/Z-isomerization of the side chain: Both photo-isomers of PpFABLA-co-PBLA (11) form a helix that─at a concentration of 16%(w/w)─form an LLC. Despite the absence of a change in the secondary structure, the E/Z-isomerization of the side chain changes the morphology of the liquid crystal and leads to different sets of dipolar coupling for the same probe molecule.

NMR Discrimination of d- and l-α-Amino Acids at Submicromolar Concentration via Parahydrogen-Induced Hyperpolarization

Differentiation of enantiomers represents an important research area for pharmaceutical, chemical, and food industries. However, enantiomer separation is a laborious task that demands complex analytical techniques, specialized equipment, and expert personnel. In this respect, discrimination and quantification of d- and l-α-amino acids is no exception, generally requiring extensive sample manipulation, including isolation, functionalization, and chiral separation. This complex sample treatment results in high time costs and potential biases in the quantitative determination. Here, we present an approach based on the combination of non-hydrogenative parahydrogen-induced hyperpolarization and nuclear magnetic resonance that allows detection, discrimination, and quantification of d- and l-α-amino acids in complex mixtures such as biofluids and food extracts down to submicromolar concentrations. Importantly, this method can be directly applied to the system under investigation without any prior isolation, fractionation, or functionalization step.

Identification and differentiation of aldose enantiomers in trace natural glycosides by ultra-performance liquid chromatography with diode array detector coupled to quadrupole/time-of-flight mass spectrometry combined with one-pot derivatized protocol

Trace natural products usually possess great biological activity, but the identification of the absolute configuration of monosaccharides in trace natural glycosides is still a challenge. The methods available are not suitable to distinguish enantiomers of monosaccharides in trace natural products when the amount of natural products is less than 1.0 mg. Therefore, this study explored an ultra-performance liquid chromatography with diode array detector coupled to quadrupole/time-of-flight mass spectrometry (UPLC-DAD-Q-TOF/MS) combined with modified one-pot monosaccharide derivatized protocol to distinguish enantiomers of monosaccharides in trace natural products. The experimental parameters were optimized to achieve multiple objectives, and detailed approaches were proposed to improve the sensitivity and resolution of the protonated ion and adduct ion of the monosaccharide derivatives. The retention time of the extracted ion chromatogram and the relative abundance ratio of the characteristic fragment ions were considered for the characterization of the absolute configuration of monosaccharides to distinguish the enantiomers of the monosaccharides of natural products. This strategy was successfully applied to distinguishing 8 pairs of aldose enantiomers, and was verified using trace D-lactose and trace narirutin, which are reference substances commercially available. Moreover, the absolute configuration of the monosaccharide of one trace new compound isolated from the seeds of Moringa oleifera Lam. was successfully identified using this procedure.

Differentiation of Epoxide Enantiomers in the Confined Spaces of an Homochiral Cu(II) Metal-Organic Framework by Kinetic Resolution.

TAMOF‐1, a homochiral metal‐organic framework (MOF) constructed from an amino acid derivative and Cu(II), was investigated as a heterogeneous catalyst in kinetic resolutions involving the ring opening of styrene oxide with a set of anilines. The branched products generated from the ring opening of styrene oxide with anilines and the unreacted epoxide were obtained with moderately high enantiomeric excesses. The linear product arising from the attack on the non‐benzylic position of styrene oxide underwent a second kinetic resolution by reacting with the epoxide, resulting in an amplification of its final enantiomeric excess and a concomitant formation of an array of isomeric aminodiols. Computational studies confirmed the experimental results, providing a deep understanding of the whole process involving the two successive kinetic resolutions. Furthermore, TAMOF‐1 activity was conserved after several catalytic cycles. The ring opening of a meso‐epoxide with aniline catalyzed by TAMOF‐1 was also studied and moderate enantioselectivities were obtained.

Intercepting fleeting cyclic allenes with asymmetric nickel catalysis.

Strained cyclic organic molecules, such as arynes, cyclic alkynes and cyclic allenes, have intrigued chemists for more than a century with their unusual structures and high chemical reactivity1. The considerable ring strain (30-50 kilocalories per mole)2,3 that characterizes these transient intermediates imparts high reactivity in many reactions, including cycloadditions and nucleophilic trappings, often generating structurally complex products4. Although strategies to control absolute stereochemistry in these reactions have been reported using stoichiometric chiral reagents5,6, catalytic asymmetricvariants to generate enantioenriched products have remained difficult to achieve. Here we report the interception of racemic cyclic allene intermediates in a catalytic asymmetric reaction and provide evidence for two distinct mechanisms that control absolute stereochemistry in such transformations: kinetic differentiation of allene enantiomers and desymmetrization of intermediate π-allylnickel complexes. Computational studies implicate a catalytic mechanism involving initial kinetic differentiation of the cyclic allene enantiomers through stereoselective olefin insertion, loss of the resultant stereochemical information, and subsequent introduction of absolute stereochemistry through desymmetrization of an intermediate π-allylnickel complex. These results reveal reactivity that is available to cyclic allenes beyond the traditional cycloadditions and nucleophilic trappings previously reported, thus expanding thetypes of product accessible from this class of intermediates. Additionally, our computational studies suggest two potential strategies for stereocontrol in reactions of cyclic allenes. Combined, these results lay the foundation for the development of catalytic asymmetric reactions involving these classically avoided strained intermediates.

The Impact of Solvent and the Receptor Structure on Chiral Recognition Using Model Acyclic Bisamides Decorated with Glucosamine Pendant Arms.

We investigated the influence of various factors (including solvent mixtures) on chiral recognition of chiral carboxylates, using the titration method under 1H NMR control. We found that strong binding carboxylates (geometrical matching) is not enough for the satisfactory differentiation of enantiomers. Moreover, solvent mixture studies indicate a significant influence of environment on the formation of diastereomeric complexes and variations among them. Our findings offer insights into the complementarity of chiral recognition processes.

Polydopamine/Silver Substrates Stemmed from Chiral Silica for SERS Differentiation of Amino Acid Enantiomers.

Polydopamine (PDA) and silver (Ag) nanoparticles were first generated on chiral silica nanofibers and then detached from silica to form PDA/Ag composites. The as-obtained PDA/Ag showed surface-enhanced Raman scattering (SERS) activity but very weak circular dichroism optical activity. Interestingly, the PDA/Ag substrates could make a pair of tyrosine (or phenylalanine) enantiomers show different Raman scattering signal intensities, where the differences could reach 3 times. In contrast, PDA/Ag prepared by using racemic or achiral silica did not exhibit such discrimination performance. Therefore, this research offered a novel SERS-based enantiomeric differentiation method with the assistance of plasmonic metal-containing substrates stemmed from intrinsically chiral inorganic silica.

Ultrasound-assisted synthesis of chiral cysteine-capped CdSe quantum dots for fluorometric differentiation and quantitation of tryptophan enantiomers.

A room temperature ultrasound-assisted method was applied to synthesize L- and D-cysteine-capped CdSe quantum dots (QDs). The QDs were characterized by XRD, FT-IR, and TEM. They have diameters of 5-7nm and are shown to be viable probes for highly selective chiral recognition of tryptophan (Trp) enantiomers by fluorometry. The green fluorescence of the capped QDs (with excitation/emission maxima at 380/527nm and 380/520nm for L-Cys and D-Cys QDs, respectively) is differently quenched by D- and L-Trp in a high selective manner, with negligible interference by other species. The calibration plots and corresponding Stern-Volmer plots for both Trp enantiomers were investigated by two different approaches: In the first, each individual enantiomer was tested. In the second, each enantiomer was tested in the presence of a 100-folds excess of the other enantiomer. The detection limits for the recognition of L- and D-Trp are 4.2 and 4.7nM, respectively, for the first approach. In the presence of the other enantiomer, the LODs are 4.4 and 4.8nM. The linear range extends from 0.1 to 15μM for both enantiomers. Graphical abstractSchematic representation of tryptophan (Trp) chiral recognition process. The fluorescence (green, ON) of D- and L-Cys (cysteine)-capped CdSe QDs is quenched (black, OFF) through a preferential and selective interaction with L- and D-Trp, respectively.

Accessible Superchiral Near-Fields Driven by Tailored Electric and Magnetic Resonances in All-Dielectric Nanostructures

Detection and differentiation of enantiomers in small quantities are crucially important in many scientific fields, including biology, chemistry, and pharmacy. Chiral molecules manifest their hande...

Enantioselective Dynamic Self-Assembly of Histidine Droplets on Pillar[5]arene-Modified Interfaces.

The self-assembly of macroscopic droplets on interfaces has attracted much attention and shown promising potential in the field of materials as a sensing or delivery system. Herein, we reported a new strategy to construct a d-tartaric acid-functionalized pillar[5]arene (d-TP5) interface for macroscopic differentiation of histidine enantiomers. At the molecular level, it has been proved that d-TP5 has the ability to distinguish between l-Histidine and d-Histidine ( KL/ KD = 4.6). Furthermore, a functional d-TP5 surface was constructed by a click reaction and characterized by contact angle measurements and attenuated total reflection-Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy analyses. The d-TP5 surface exhibited the selective dynamic adhesion of l-His droplets on the tilted interface. It means that a d-TP5 surface can distinguish histidine enantiomers at a macrolevel. The amount of d/l-His absorbed by a d-TP5 surface and the morphology of His particles formed by removing the solvent have been investigated to prove that the self-assembly of His occurs on the d-TP5 surface. The possible mechanism has been discussed from host-guest interaction and chiral recognition. The proposed chiral material displays rapidly remarkable selectivity and is convenient to be utilized, which should be suitable for comprehending chiral recognition processing and applied to chiral recognition detection of histidine in a living body.

Sensing Chirality with Rotational Spectroscopy.

Chiroptical spectroscopy techniques for the differentiation of enantiomers in the condensed phase are based on an established paradigm that relies on symmetry breaking using circularly polarized light. We review a novel approach for the study of chiral molecules in the gas phase using broadband rotational spectroscopy, namely microwave three-wave mixing, which is a coherent, nonlinear, and resonant process. This technique can be used to generate a coherent molecular rotational signal that can be detected in a manner similar to that in conventional Fourier transform microwave spectroscopy. The structure (and thermal distribution of conformations), handedness, and enantiomeric excess of gas-phase samples can be determined unambiguously by employing tailored microwave fields. We discuss the theoretical and experimental aspects of the method, the significance of the first demonstrations of the technique for enantiomer differentiation, and the method's rapid advance into a robust choice to study molecular chirality in the gas phase. Very recently, the microwave three-wave mixing approach was extended to enantiomer-selective population transfer, an important step toward spatial enantiomer separation on the fly.

「鏡の家」のミルクの味 : 鏡像異性体を区別する(化学への招待)

「鏡の家」のミルクの味 : 鏡像異性体を区別する(化学への招待)

ChemInform Abstract: Enantioselective Gas Chromatography in Search of the Origin of Biomolecular Asymmetry in Outer Space

AbstractReview: [67 refs.

Enantioselective Gas Chromatography in Search of the Origin of Biomolecular Asymmetry in Outer Space

AbstractSince the pioneering work of Emanuel Gil‐Av and his associates at the Weizmann Institute of Science the direct gas chromatographic resolution of enantiomers has found its application in different fields of natural sciences, even expanding to space research and astrobiology. In these domains the resolution of chiral molecules of prebiotic relevance is of particular interest, since the determination of ratios between l‐ and d‐enantiomers within non‐terrestrial samples is assumed to shed light on the origin of biomolecular homochirality and the beginnings of life itself. According to an astrophysical scenario, the first molecular symmetry breaking event occurred upon irradiation of chiral organic molecules with circularly polarized light present in the interstellar medium. To examine this hypothesis, among others, chiral gas chromatographic stationary phases have been widely used to provide the differentiation of enantiomers in extracts of meteorites, samples of simulated interstellar ices and Mars soil analogues. Moreover several chiral capillary columns have been selected for in situ analyses of extraterrestrial organic matter by Mars missions and the cometary Rosetta mission. This review will highlight current advances of enantioselective gas chromatography applied to space science.

ChemInform Abstract: Chiral NMR Solvating Additives for Differentiation of Enantiomers

AbstractReview: 276 refs.