Chirality最新文献

(S)-Bepotastine is a highly selective histamine H1-receptor antagonist in the treatment of allergic rhinitis and other allergic diseases. We achieved a facile and convenient synthesis of (S)-bepotastine by resolving an early stage synthetic precursor. We devised a new class of resolving agent, BINOL-3,3′-dicarboxylic acid which could be considered as an axial version of tartaric acid. As the first example, we successfully resolved racemic piperidinyl ether by (S)-BINOL-3,3′-dicarboxylic acid with high optical purity. The final installation is quite straightforward and readily accomplished without any chiral loss.

As one of the most widely used fungicides in global agriculture, chiral triazole fungicides play a crucial role in crop protection due to their broad-spectrum efficacy. However, the environmental problems caused by their widespread use are becoming increasingly prominent. These problems not only cause ecological pollution but also pose potential risks to human health and the safety of ecosystems. In response to these problems, developing optically pure monomer pesticides that are highly efficient yet low in toxicity has become a key strategy. This reduces both the dosage required and the impact on nontarget organisms. In recent years, the research focus on chiral triazole fungicides has expanded from evaluating a single biological activity to assessing stereoselective toxicity, environmental behavior, and metabolic fate in a multidimensional way. Despite growing academic interest in the stereoselective toxicological effects and metabolic differences of nontarget organisms (particularly mammals), most available reviews have focused on biological activity and environmental fate. Furthermore, there is a lack of reviews that systematically evaluate the stereoselective behavior of these pesticides in mammals, which restricts our overall understanding of the safety of this class of pesticides. Based on this, this paper not only lists the stereoselective bioactivities and toxicological differences of chiral triazole fungicides but also, for the first time, focuses on the mammalian system, providing a comprehensive elucidation of their stereoselective behaviors from the perspectives of metabolism in rat liver microsomes, toxicokinetic characteristics, metabolomics, and gut microbiota. The aim of this review is to address the shortcomings of existing reviews and to serve as a reference for the development of optically pure, environmentally friendly, low-toxicity, and efficient monomer pesticides.

Molecular homochirality — the uniformity of chirality in biological molecules — is a fundamental feature of life, yet its origins remain unresolved. The correspondence between the chirality of biological monomers on Earth and that observed in ancient meteorites implies a systematic selection of chirality sign in prebiotic chemistry, rather than a stochastic process. While classical theories attribute symmetry breaking to chiral autocatalysis, such self-amplifying processes are rare and have not been empirically demonstrated in the synthesis of amino acids and carbohydrates. In contrast, chiral cross-catalysis between amino acids and carbohydrates — a mechanism consistent with known chemical behavior — could similarly amplify chiral purity. However, cross-catalysis alone cannot determine the chirality sign due to its inherent symmetry, leaving the origin of the initial bias unexplained. Although weak interactions have been proposed as a potential source of this bias, their effects are theoretically negligible, raising questions about their sufficiency. Our kinetic analysis of cross-catalytic systems reveals that even an infinitesimal preference for left-handed amino acids and right-handed carbohydrates could be sufficient to establish the homochirality observed in life. This mechanism provides a plausible link between prebiotic chemistry and the homochirality of the biosphere, offering a potential resolution to this longstanding enigma.

This study represents a special, time-dependent resolution strategy of an atropisomeric, bifunctional 1-phenylpyrrole derivative, using the nonactive enantiomer of the key amine intermediate Apremilast as an efficient resolving agent. Among the solvents investigated, ethyl acetate was identified as the optimal solvent, allowing rapid crystallization and high enantiomeric purity (> 99% ee). A detailed study of kinetic behavior revealed that early-stage crystallization and timely separation of diastereomeric salt are critical to achieving high enantiopurity and avoiding recrystallization to lead to a racemic product. Time-dependent studies suggest that solvate formation of enantiomers and ethyl acetate plays a crucial role in the resolution mechanism. This resolution process enables the direct separation of racemic 2-(2-carbamoyl-1H-pyrrol-1-yl)-3-(trifluoromethyl) benzoic acid suitable for further applications, such as resolving agents for amine-type compounds. Significantly, this approach recycles an amine-type drug intermediate that is typically discarded during the large-scale production of Apremilast, thus being in line with green chemistry principles by minimizing waste and enabling resource recovery.

A recent publication by Kopec et al., “The effect of enantiomers of thalidomide on colon cells-Raman spectroscopy studies”, reported to “demonstrate that Raman spectroscopy reveals distinct spectral differences between the enantiomers of thalidomide” and provided both experimental and computational evidence. However, the theory of Raman spectroscopy inherently establishes that two enantiomers must exhibit identical Raman frequencies and intensities. While the slightly different experimental Raman spectra for the two enantiomers of thalidomide can be traced back to samples with different chemical and/or optical purities, the significant discrepancies observed in the computed Raman spectra arise from a computational artifact related to methodological shortcomings.

The enantiomeric purity of Finerenone (FIN), a novel therapeutic for chronic kidney disease (CKD), is a critical quality attribute for ensuring patient safety. This study reports the first chiral HPLC method for the simultaneous determination of FIN and its enantiomer, developed and validated using a rigorous analytical quality by design (AQbD) framework. The method employs a CHIRALPAK AD-H column with an isocratic mobile phase of n-hexane: ethanol (62:38, v/v). Optimized conditions provide excellent baseline resolution (Rₛ = 3.5) in under 10 min. The method was validated using accuracy profiles, demonstrating high performance with limits of quantification established at 340 μg mL⁻¹ for FIN and 0.40 μg mL⁻¹ for its 4R enantiomer. The AQbD approach successfully defined a robust method operable design region (MODR) to ensure consistent performance. Furthermore, a multimetric sustainability evaluation confirmed the method's favorable eco-profile, achieving a Grade Index (BAGI) score of 77.5 and Red-Green-Blue 12 (RGB12) score of 80.8. This work provides a reliable, robust, and eco-conscious analytical tool essential for the quality control of FIN formulations.

Ketoprofen, also known as (RS)-2-(3-benzoylphenyl)-propionic acid, has the molecular formula C₁₆H₁₄O₃ and is classified as a non-steroidal anti-inflammatory medication. R-ketoprofen has stronger analgesic effects than S-K, and as a result, there is a growing interest in enantio-recognition research, which may be accomplished through supramolecular interactions, particularly host-guest reactions. A 1:1 molar ratio was used to produce the combination of separate RK and SK and a 0.01 M stock solution of HP-β-CD to get the final concentration of 6 × 10⁻⁴ M. Ethanol was used to make stock solutions of ketoprofen enantiomers (1 mM). Researchers combined a specific volume of ketoprofen with 2-hydroxypropyl-beta-cyclodextrin (HPβ-CD) and then used spectroscopic methods to study how the S-ketoprofen (SK) and R-ketoprofen (RK) enantiomers interact with HPβ-CD to form inclusion complexes in an aqueous solution. The Benesi–Hildebrand plot was used to determine the inclusion complexes' stoichiometry ratio and binding constant; both enantiomers displayed a 1:1 stoichiometry ratio inclusion complex with HP-β-CD. Compared with SK (799 M⁻¹), RK has a higher binding constant (1038 M⁻¹). These results showed that HP-β-CD preferred to form inclusion complexes with RK over SK. At neutral pH, there are significant differences between RK and SK when HP-β-CD is present.

Specific rotations [α] of L-arginine in water and aqueous solutions of glycine, HCl, LiCl, KCl, NaOH, and Na₂SO₄ were measured at 405 nm. The [α] value is 34.7 ± 0.5 deg·mL·dm⁻¹·g⁻¹ in water and increases with the increasing acidity in accordance with the Clough–Lutz–Jirgensons (CLJ) rule. [α] changes little in glycine solutions, implying that the CLJ effect is the result of a proton-amino acid interaction. In the salt solutions, [α] gradually decreases with the increasing concentration, suggesting that binding between a metal ion and L-arginine produces a different structure from that of the protonated amino acid, producing the anti-CLJ effect.

In this work, the silica gel bonded amylose[(S)-α-methylbenzyl carbamate] (CHIRALPAK IH) was chosen as the chiral stationary phase (CSP) for the separation of five quinolone enantiomers by high-performance liquid chromatography (HPLC), namely, ofloxacin, flumequine, nadifloxacin, lomefloxacin, and clinafloxacin. The mobile phase composition, organic modifier, and acid–base additive were systematically investigated for the baseline separation of these five interested quinolones. The optimized mobile phases were n-hexane–ethanol–acetic acid–diethylamine (60:40:0.2:0.2, v/v/v/v) for ofloxacin and nadifloxacin, n-hexane–ethanol–acetic acid–diethylamine (60:40:0.2:0.2, v/v/v/v) for flumequine, n-hexane–isopropanol–acetic acid–diethylamine (60:40:0.3:0.3, v/v/v/v) for lomefloxacin, and n-hexane–ethanol–acetic acid–diethylamine (70:30:0.3:0.3, v/v/v/v) for clinafloxacin. The interaction forces between the amylose CSP and target quinolones were simulated by computerized molecular docking to study their enantiorecognition mechanisms. The results indicated that hydrogen bonding, π–π stacking, and hydrophobic interactions collectively contributed to the stereoselective binding. The differences in these interaction forces between the quinolone enantiomers, particularly the greater contribution of hydrogen bonding in one enantiomer compared to the other, led to a significant difference in binding energy. This differential binding energy ultimately governed the elution order and enabled chiral recognition of the five quinolone enantiomers.

As enantiomers can have different pharmacological and toxicological impacts even though they have the analogous chemical composition, efficient chiral separation is crucial. Chromatography is one of the primary methods for separating enantiomers, and the key to chromatographic separation lies in the chiral stationary phase (CSP). Chiral porous materials have emerged as innovative chiral stationary phases and garnered extensive attention. Zr based MOF materials, have been regarded as one of the most stable metal–organic framework (MOF) materials. In this paper, after grafting with L-proline, UiO-66 was used for the first time for chiral gas chromatography separation. The newly developed CSP provided high resolution for xylenes within only 2–3 min. For substances like linalool, α-pinene, and xylenes, the UiO-66-NH₂-L-Pro–coated capillary column acquired bas3ic resolution and showed outstanding enantiomeric and positional isomer isolation. Comprehensive characterizations, including SEM, XRD, FT-IR, TGA, N₂ adsorption–desorption isotherms, CD spectra, and XPS, were conducted to analyze the material stucture and chiral recognition mechanism. The chiral separation relies on transient diastereomeric complexes formed between L-proline and enantiomers, stabilized by hydrogen bonding, intermolecular forces, and steric constraints within UiO-66's micropores. These interactions enforce enantioselective discrimination via the pore's stereochemical filtering, enabling chiral resolution. This study is expected to provide significant value for both chromatographic chiral separation and large-scale chiral substance separation.