Chiral Compounds Research Articles

Circularly polarized peroxyoxalate chemiluminescence with chiral activators

A series of planar chiral macrocyclic compounds derived from [2.2]-paracyclophane scaffold and helicenes in enantiomers were synthesized and found to be efficient circularly polarized emitters. These chiral macrocyclic compounds and helicenes were used as activators in peroxyoxalate chemiluminescence. Among the blue, green, or yellow chemiluminescent activators, compound 2R containing electron-donating dimethylamino groups with lowest oxidation potential showed the best chemiluminescence quantum yield of 0.21% (higher than 0.17% of 9,10-diphenylanthracene at the concentration of 1.0 × 10−4 mol dm−3). Appreciable circularly polarized chemiluminescence with dissymmetry factors (|gCL|) in the range of 1.4 × 10−3−5.4 × 10−3 have been recorded for these chiral chemiluminescent activators.

Bio-Approach for Obtaining Enantiomerically Pure Clopidogrel with the Use of Ionic Liquids.

Clopidogrel is a chiral compound widely used as an antiplatelet medication that lowers the risk of blood clots, strokes, and heart attacks. The main aim of the study presented herein was to obtain (S)-clopidogrel, which is commercially available in treatments, via the kinetic resolution of racemic clopidogrel carboxylic acid with the use of lipase from Candida rugosa and a two-phase reaction medium containing an ionic liquid. For this purpose, the enantioselective biotransformation of clopidogrel carboxylic acid and chiral chromatographic separation with the use of a UPLC-MS/MS system were optimized. The best kinetic resolution parameters were obtained by using a catalytic system containing lipase from Candida rugosa OF as a biocatalyst, cyclohexane and [EMIM][BF4] as a two-phase reaction medium, and methanol as an acyl acceptor. The enantiomeric excess of the product was eep = 94.21% ± 1.07 and the conversion was c = 49.60% ± 0.57%, whereas the enantioselectivity was E = 113.40 ± 1.29. The performed study proved the possibility of obtaining (S)-clopidogrel with the use of lipase as a biocatalyst and a two-phase reaction medium containing an ionic liquid, which is in parallel with green chemistry methodology and does not require environmentally harmful conditions.

Synthesis and Chiral Separation of Some New Derivatives of Imidazo [1, 2- a] Pyridine

Introduction: Mannich base is the result of the three-part chemical reaction known as the Mannich reaction, which includes the amino alkylation of an acidic proton adjacent to a carbonyl group by formaldehyde and either a primary or secondary amine. Method:: In a 1L flask, dissolve 28.2 g (0.3 mol) of 2-aminopyridine, and 400mL of ethanol, then add 32.6g (0.3 mol) of chloroacetone and put 30 drops of acetic acid. The organic phases are combined and dried with Magnesium sulfate. After solvent evaporation, we have recovered our product which is a 2-methylimidazo [1, 2-a] pyridine product. Result: A C-18 bonded stationary phase provided one significant peak for all of the compounds under examination providing solid proof of the compound purity. This was used to demonstrate the purity of the compounds. Then, the potential enantiomers of these chiral compounds were obtained using the four CSPs. Conclusion: In this study, several novel Mannich bases were prepared. These bases had rendement ranging from 76 to 94.73, and their chiral separation was discussed utilizing four polysaccharide-based CSPs: ChiralpakAS, Chiralcel OD, Chirapak®AS-3R, and Chiralcel OJ.

Synthesis of Functionalized ABAC- and ABCD-Type Inherently Chiral Heteracalix[4]aromatics.

Despite their interesting stereochemistry and potential applications in (supramolecular) chemistry and chiroptical materials, inherently chiral macrocyclic compounds remain rare and are largely unexplored. We report herein a fragment coupling method to construct ABAC- and ABCD-type inherently chiral heteracalix[4]aromatics. The synthesis involves SNAr CuI-catalyzed Ullmann coupling and aliphatic nucleophilic substitution reactions as key steps using readily available starting materials. Postmacrocyclization functionalization reactions enabled the production of amino-substituted and (benzo[d])imidazole-2-(thi)one-bearing heteracalix[4]aromatics. Enantiopure ABCD-type macrocycles were obtained from resolution.

Universal and divergent P-stereogenic building with camphor-derived 2,3-diols

The access to P-stereogenic motifs has always been considered a very challenging and high attractive mission in modern organic synthesis. While several chiral auxiliaries employed by the practical Jugé-Stephan-like methodology have been developed, new type of readily accessible bifunctional ligands toward P-stereogenic building still remain much desirable. Herein, we present a powerful chiral template, camphor-derived 2,3-diols named CAMDOL, which were designed and synthesized from the commercially cheap camphorquinone in high yields at 50 grams scale with a column-free purification. Diverse P(III)-chiral compounds and their borane forms including phosphinous acids, phosphinites, and phosphines, as well as the corresponding P(V)-chiral compounds including phosphinates, phosphine oxides, phosphinothioates, phosphine sulfides, and secondary phosphine oxides were afforded in high yields and ee values through the optimal 2,3-diphenyl CAMDOL platform. An unusual C3-OP bond cleavage following the first P-OC2 bond breaking was observed during the ring-opening process when quenching by NH4Cl solution, which generates a unique but valuable camphor-epoxide scaffold as by-product.

Chiral Phosphoric Acid-Catalyzed Enantioselective Synthesis of Axially Chiral Compounds Involving Indole Derivatives.

Indoles are one of the most ubiquitous subclass of N-heterocycles and are increasingly incorporated to design new axially chiral scaffolds. The rich profile of reactivity and N-H functionality allow chemical derivatization for enhanced medicinal, material and catalytic properties. Although asymmetric C-C coupling of two arenes gives the most direct access of axially chiral biaryl scaffolds, this chemistry has been the remit of metal catalysis and works efficiently on limited substrates. Our group has devoted special interest in devising novel organocatalytic arylation reactions to fabricate biaryl atropisomers. In this realm, indoles and derivatives have been reliably used as the arylation partners in combination with azoarenes, nitrosonapthalenes and quinone derivatives. Their efficient interaction with chiral phosphoric acid catalyst as well as the tunability of electronics and sterics have enabled excellent control of stereo-, chemo- and regioselectivity to furnish diverse scaffolds. In addition, indoles could act as nucleophiles in desymmetrization of 1,2,4-triazole-3,5-diones. This account provides a succinct illustration of these developments.

Homochiral organic molecular cage RCC3-R-modified silica as a new multimodal and multifunctional stationary phase for high-performance liquid chromatography.

In this work, homochiral reduced imine cage was covalently bonded to the surface of the silica to prepare a novel high-performance liquid chromatography stationary phase, which was applied for the multiple separation modes such as normal phase, reversed-phase, ion exchange, and hydrophilic interaction chromatography. The successful preparation of the homochiral reduced imine cage bonded silica stationary phase was confirmed by performing a series of methods including X-ray photoelectron spectroscopy, thermogravimetric analysis, and infrared spectroscopy. From the extracted results of the chiral resolution in normal phase and reversed-phase modes, it was demonstrated that seven chiral compounds were successfully separated, among which the resolution of 1-phenylethanol reached the value of 3.97. Moreover, the multifunctional chromatographic performance of the new molecular cage stationary phase was systematically investigated in the modes of reversed-phase, ion exchange, and hydrophilic interaction chromatography for the separation and analysis of a total of 59 compounds in eight classes. This work demonstrated that the homochiral reduced imine cage not only achieved multiseparation modes and multiseparation functions performance with high stability, but also expanded the application of the organic molecular cage in the field of liquid chromatography.

Asymmetric Access to Boryl-Substituted Vicinal Aminoalcohols through Cu-Catalyzed Reductive Coupling.

Herein, we report the development of a Cu-catalyzed enantioselective borylative aminoallylation of aldehydes using a N-substituted allene to access boryl-substituted 1,2-aminoalcohol synthons for diversification to chiral heteroatom-rich organic compounds. The reported reaction provides access to several different substitution patterns of chiral 1,2-aminoalcohol products from the same readily available starting materials with high diastereo- and enantioselectivity.

SYNTHESIS AND POLYMERIZATION OF N,N-DI(β-CHLOR)ALLYLAMINO- ETHANIC ACID

Amino acids are chiral compounds that make up proteins and play an important role in biochemical processes in living organisms. They are widely used as building blocks in organic synthesis, components of asymmetric synthesis catalysts, separating agents, etc. To this end, we found that the interaction of 1 mol aminoethanic acid with 2 mol of (β-chlor)allyl chloride in an aqueous solution of sodium hydroxide leads to the formation of a new monomer – N,N-di(β-chlor)allylamino ethanic acid (BEA) with a yield of ~45%. When carrying out the polymerization of BEA in an aqueous solution in the presence of ammonium persulfate with an initiator concentration of 4·10-4–5·10-3 mol/l , water-soluble polymers with sufficiently high values of reduced viscosity ([η] = 0.16–0.18 dl/q) for the indicated amino acid were obtained. It was found that polymerization proceeds along the double bonds of diallyl groups according to the cyclolinear mechanism with a pyrrolidine structure

Catalytic Atroposelective Aerobic Oxidation Approaches to Axially Chiral Molecules.

A copper and chiral nitroxide co-catalyzed aerobic enantioselective oxidation process has been developed that allows access to axially chiral molecules. Two complementary atroposelective approaches, oxidative kinetic resolution (OKR) and desymmetrization, were studied using ambient air as the stoichiometric terminal oxidant. OKR of rac-N-arylpyrrole alcohols and rac-biaryl alcohols affords the optically pure compounds with er up to 3.5:96.5 and 5.5:94.5, respectively. Desymmetrization of prochiral diols provides axially chiral biaryl compounds with er up to 99:1.

Chiral Recognition by Supramolecular Porphyrin–Hemicucurbit[8]uril-Functionalized Gravimetric Sensors

Enantiorecognition of a chiral analyte usually requires the ability to respond with high specificity to one of the two enantiomers of a chiral compound. However, in most cases, chiral sensors have chemical sensitivity toward both enantiomers, showing differences only in the intensity of responses. Furthermore, specific chiral receptors are obtained with high synthetic efforts and have limited structural versatility. These facts hinder the implementation of chiral sensors in many potential applications. Here, we utilize the presence of both enantiomers of each receptor to introduce a novel normalization that allows the enantio-recognition of compounds even when single sensors are not specific for one enantiomer of a target analyte. For this purpose, a novel protocol that permits the fabrication of a large set of enantiomeric receptor pairs with low synthetic efforts by combining metalloporphyrins with (R,R)- and (S,S)-cyclohexanohemicucurbit[8]uril is developed. The potentialities of this approach are investigated by an array of four pairs of enantiomeric sensors fabricated using quartz microbalances since gravimetric sensors are intrinsically non-selective toward the mechanism of interaction of analytes and receptors. Albeit the weak enantioselectivity of single sensors toward limonene and 1-phenylethylamine, the normalization allows the correct identification of these enantiomers in the vapor phase indifferent to their concentration. Remarkably, the achiral metalloporphyrin choice influences the enantioselective properties, opening the way to easily obtain a large library of chiral receptors that can be implemented in actual sensor arrays. These enantioselective electronic noses and tongues may have a potential striking impact in many medical, agrochemical, and environmental fields.

Atropselective Organocatalytic Synthesis of Chiral Compounds Containing Nitrogen along the Axis of Chirality

Atropisomers, i.e., stereoisomers that are distinct because their free rotation about a single bond is hindered by steric interactions between nearby bulky groups or by electrostatics, may interact with their surroundings in different ways, and may also exhibit different properties. They may be found as natural products, as pharmaceutical or agricultural active ingredients, as chiral ligands and organocatalysts, and in functional materials. Our ability to synthesize them stereoselectively and in a sustainable way, using achiral materials and simply with the aid of an organocatalyst and mild conditions, has become a hot topic in research. This review provides an overview of recent achievements in the synthesis of atropisomers containing C-N and N-N axes of chirality.

Investigation of the Influence of Pressure on the Physical Properties and Superconducting Transition Temperature of Chiral Noncentrosymmetric TaRh2B2 and NbRh2B2.

TaRh2B2 and NbRh2B2 compounds exhibit noncentrosymmetric superconductivity with a chiral structure. Density functional theory-based ab-initio calculations have been executed to analyze the structural properties, mechanical stability, ductility/brittleness behaviors, Debye temperature, melting temperature, optical response to incident photon energy, electronic characteristics, and superconducting transition temperature of chiral TaRh2B2 and NbRh2B2 compounds under pressure up to 16 GPa. Both the chiral phases are mechanically stable and exhibit ductile nature under the studied pressure. The maximum value of the Pugh ratio (an indicator of ductile/brittle behaviors) is observed to be 2.55 (for NbRh2B2) and 2.52 (for TaRh2B2) at 16 GPa. The lowest value of the Pugh ratio is noticed at 0 GPa for both these chiral compounds. The analysis of reflectivity spectra suggests that both the chiral compounds can be used as efficient reflecting materials in the visible energy region. At 0 GPa, the calculated densities of states (DOSs) at the Fermi level are found to be 1.59 and 2.13 states eV-1 per formula unit for TaRh2B2 and NbRh2B2, respectively. The DOS values of both the chiral phases do not alter significantly with applied pressure. The shape of the DOS curve of both compounds remains almost invariant with applied pressure. The pressure-induced variation of Debye temperatures of both compounds is observed, which may cause the alternation of the superconducting transition temperature, Tc, with applied pressure. The probable changing of Tc with pressure has been analyzed from the McMillan equation.

Synthesis of Thiophene-Based Derivatives and the Effects of Their Molecular Structure on the Mesomorphic Behavior and Temperature Range of Liquid-Crystalline Blue Phases

The development of blue-phase liquid crystal (BPLC) materials with a wide temperature range is of great significance for practical applications in the optoelectronic field. In the study, bent-core derivatives with a 3-hexyl-2,5-disubstituted thiophene central ring in the λ-shaped molecular structure were designed and synthesized. Their mesomorphic behavior and effect on the blue-phase (BP) temperature range were investigated. Interestingly, a BP was achieved both during the heating and cooling processes by doping with a proper concentration of chiral compound into the thiophene bent-shaped molecule with high rigidity, while derivatives with fluorine atom substitution only exhibited cholesteric phase no matter how many chiral compounds were added. This result proved that BP is highly sensitive to the molecular structures of bent-shaped molecules. Moreover, the BP temperature range was broadened when adding these molecules into a BPLC host, which thus improved the BP temperature range from the initial value, no more than 4 °C, to as much as 24 °C. The experimental phenomena were reasonably explained through molecular simulation calculations. The study may provide some experimental basis and theoretical guidance for the design of novel bent-shaped molecules and BPLC material with a wide temperature range.

Biochemical and structural insight into the chemical resistance and cofactor specificity of the formate dehydrogenase from Starkeya novella.

Formate dehydrogenases (Fdhs) mediate the oxidation of formate to carbon dioxide and concomitant reduction of nicotinamide adenine dinucleotide (NAD+ ). The low cost of the substrate formate and importance of the product NADH as a cellular source of reducing power make this reaction attractive for biotechnological applications. However, the majority of Fdhs are sensitive to inactivation by thiol-modifying reagents. In this study, we report a chemically resistant Fdh (FdhSNO ) from the soil bacterium Starkeya novella strictly specific for NAD+ . We present its recombinant overproduction, purification and biochemical characterization. The mechanistic basis of chemical resistance was found to be a valine in position 255 (rather than a cysteine as in other Fdhs) preventing the inactivation by thiol-modifying compounds. To further improve the usefulness of FdhSNO as for generating reducing power, we rationally engineered the protein to reduce the coenzyme nicotinamide adenine dinucleotide phosphate (NADP+ ) with better catalytic efficiency than NAD+ . The single mutation D221Q enabled the reduction of NADP+ with a catalytic efficiency kCAT /KM of 0.4 s-1 ·mm-1 at 200 mm formate, while a quadruple mutant (A198G/D221Q/H379K/S380V) resulted in a fivefold increase in catalytic efficiency for NADP+ compared with the single mutant. We determined the cofactor-bound structure of the quadruple mutant to gain mechanistic evidence behind the improved specificity for NADP+ . Our efforts to unravel the key residues for the chemical resistance and cofactor specificity of FdhSNO may lead to wider use of this enzymatic group in a more sustainable (bio)manufacture of value-added chemicals, as for instance the biosynthesis of chiral compounds.

Chiral covalent organic framework-based open tubular capillary electrochromatography column for enantioseparation of selected amino acids and pesticides.

A novel chiral covalent organic framework (CCOF) was synthesized with an imine covalent organic framework TpBD (synthesized via Schiff-base reaction between phloroglucinol (Tp) and benzidine (BD)) modified using (1S)-(+)-10-camphorsulfonyl chloride as chiral ligand by chemical bonding method for the first time, and was characterized by X-ray diffraction, Fourier-transform infrared spectra, X-ray photoelectron spectroscopy, nitrogen adsorption/desorption, thermogravimetry analysis, and zeta-potential. The results revealed that the CCOF had good crystallinity, high specific surface area and good thermal stability. Then, the CCOF was employed as stationary phase in open-tubular capillary electrochromatography (OT-CEC) column (the CCOF-bonded OT-CEC column) for enantioseparation of 21 single chiral compounds (12 natural amino acids including acidic, neutral and basic, 9 pesticides including herbicides, insecticides and fungicides) and simultaneous enantioseparation of mixture amino acids and pesticides with similar structures or properties. Under the optimized CEC conditions, all the analytes reached the baseline separation with high resolutions of 1.67-25.93 and selectivity factors of 1.06-3.49 in 8min. Finally, the reproducibility and stability of the CCOF-bonded OT-CEC column were measured. Relative standard deviations (RSDs) of retention time and separation efficiency were 0.58-4.57% and 1.85-4.98%, and not obviously changed after 150 runs. These results demonstrate that COFs-modified OT-CEC explore a promising method to separate chiral compounds.

The synergistic effects of five essential oils and eight chiral compounds on deltamethrin-piperonyl butoxide insecticide against Sitophilus zeamais (Coleoptera: Curculionidae)

The synergistic effects of five essential oils and eight chiral compounds on deltamethrin-piperonyl butoxide insecticide against Sitophilus zeamais (Coleoptera: Curculionidae)

Experimental and Theoretical Study of Biosurfactants Functionalized Gold Nanoparticles for Mixture Detection and Chiral Recognition of Tryptophan by UV-VIS Spectroscopy

Background: Tryptophan (Trp) is an essential amino acid and plays important roles in biological processes. The detection of Trp is very important for its biological and chemical study. Moreover, Trp is a chiral compound; due to its importance in biological processes, researchers have been long committed to the chiral recognition and sensing of Trp enantiomers. Methods: Two biosurfactants, sodium cholate and sodium deoxycholate, were used for the preparation of functionalized gold nanoparticles (AuNPs) which were characterized by transmission electron microscope and potentiometer. UV-Vis spectra of functionalized gold nanoparticle solutions with different concentrations of Trp, tyrosine, phenylalanine, D-Trp, and L-Trp were analyzed. Then, the discrimination mechanism was further investigated, and the promotion mechanism of biosurfactants was studied by density functional theory (DFT). Results: Trp could induce the aggregation of unmodified AuNPs in 2 h, while phenylalanine and tyrosine could not. Adding biosurfactants promoted the aggregation process, and D- Trp rather than LTrp was found to be responsible for the aggregation. Therefore, there were interaction differences not only between Trp, phenylalanine, and tyrosine but also between Trp enantiomers. Conclusions: UV-vis spectroscopy could be applied for the direct detection of Trp in mixtures as well as the chiral recognition of Trp enantiomers. DFT calculations proved that the interactions of D-Trp with biosurfactants were the strongest, which contributes to the promotion of aggregation.

Determination of dielectric properties of 5CB nematic liquid crystal doped with new chiral calamitic compounds

Determination of dielectric properties of 5CB nematic liquid crystal doped with new chiral calamitic compounds

Effective enantioselective recognition by steady-state fluorescence spectroscopy: Towards a paradigm shift to optical sensors with unusual chemical architecture.

A series of amino acid-derived 1,2,3-triazoles presenting the amino acid residue and the benzazole fluorophore connected by a triazole-4-carboxylate spacer was studied for enantioselective recognition using only steady-state fluorescence spectroscopy in solution. In this investigation, the optical sensing was performed with D-(-) and L-(+)-Arabinose and (R)-(-) and (S)-(+)-Mandelic acid as chiral analytes. The optical sensors showed specific interactions with each pair of enantiomers, allowing photophysical responses, which were used for their enantioselective recognition. DFT calculations confirm the specific interaction between the fluorophores and the analytes corroborating the observed high enantioselectivity of these compounds with the studied enantiomers. Finally, this study investigated nontrivial sensors for chiral molecules by a mechanism different than turn-on fluorescence and has the potential to broad chiral compounds with fluorophoric units as optical sensors for enantioselective sensing.