Chirality最新文献

Isatins are extensively researched compounds with diverse applications, particularly as synthetic precursors in pharmaceutical developments. However, their use as optical probes for enantioselective sensing of chiral amines has not been explored to date. Herein, we present a novel chiroptical assay with an optimized isatin that generates strong, red-shifted circular dichroism (CD) signals at approximately 380 nm upon ketimine formation with chiral amines. The intensity of the induced CD signal increases linearly with the enantiomeric excess of the analyte and thus allows quantitative chirality analysis. The general usefulness of this approach is demonstrated with a broad range of aliphatic and aromatic chiral amines, and by accurate determination of the enantiomeric composition of 10 samples.

Chiral phenylalanine derivatives are important raw materials and building blocks for the synthesis of peptides and drug molecules. Enantiomerically pure D/L-3-pyridyl- and phenylalanine has shown wide application potential in the synthesis of various drug intermediates. This article focuses on two synthetic routes from different feedstocks. The first approach is an Erlenmeyer–Plöchl route study using N-acetylglycine as starting material, whereas the second is an alkylation route study using diethyl acetamidomalonate as starting material. The key step is the resolution of N-acetamido-alanine esters using different quantities of fairly inexpensive Protamex proteinase to obtain pure enantiomeric D/L-3-pyridyl- and substituted phenylalanine or its derivative, with the ee value and purity of all products exceeding 99%. The different chiral arylalanine derivatives that can be prepared using the above two methods have good versatility.

To describe the optical activities of crystals, gyration tensors are necessary for all wavelengths of incident light. To date, few studies on direct calculations of gyration tensors from Bloch states have been conducted. Herein, a practical procedure to obtain gyration tensors of organic crystals is presented using the crystal orbital method. The extended Hückel method was adopted to evaluate the gyration tensors, epitomizing the one-electron formulation. To confirm the validity of the formulation, the optical rotatory power of alanine and γ-glycine was examined. The reproduced profiles of the optical rotatory power were consistent with the results of recent experiments. This is a general formulation of the one-electron theory of optical activities for three-dimensional crystals. In principle, the optical rotatory strength tensor is not invariant with translation. For systems with small unit cells, however, the formalism is quasi-invariant with respect to translation. The quasi origin-independent formalism is sufficiently substantial to be applicable to modern crystal optics.

Chirality in 1,4-Dihydropyrimidines influences their pharmacological properties and synthetic strategies. Enantiomers of chiral drugs often exhibit different pharmacokinetic profiles. Therefore, separating and studying individual enantiomers is crucial to optimize drug efficacy and safety. Enantiomeric separation of ±4-(4-chlorophenyl)-6-methyl-2-oxo-N-(O-toyl)-1,2,3,4-tetrahydropyrimidine-5-carboxamide (DP-1), which is a 1,4-Dihydropyrimidine derivative is achieved on CHIRALCEL® OD-H column (particle size: 5 μm, inner diameter: 4.6 mm, length:150 mm), following by investigating the kinetic properties of (R) and (S) enantiomers. The separation was achieved with a mobile phase composed of 70% (v/v) isopropyl alcohol and 30% (v/v) n-hexane. For the bioanalytical study, acetonitrile was used to precipitate the rat plasma samples and validated the method according to USFDA guidelines. The validated bioanalytical method was then successfully applied to determine the pharmacokinetic parameters of the drug in biological samples. Molecular modeling techniques, specifically docking simulations, were employed to predict the elution order of DP-1 enantiomers. The docking results revealed moderate binding interactions between the enantiomers and the chiral stationary phase (CSP), which aligns with the theoretical expectation that stronger interactions lead to longer retention times on the column.

The aim of this study was to establish a simple, fast, and sensitive method with liquid chromatography–tandem mass spectrometry (LC–MS/MS) for simultaneously determining ibuprofen enantiomers using mouse blood in very small volumes. LC–MS/MS equipped with an electrospray ionization (ESI) source was used in negative ion mode and multiple-reaction monitoring mode. Enantiomer chromatographic separation was carried out on a Lux® 5 μm Cellulose-3 (250 × 4.6 mm, 5 μm) column at a flow rate of 0.6 mL/min. Samples were pretreated by extracting only 5 μL of blood with 40 μL of acetonitrile (containing 1.3% formic acid) so that a concentration-time profile could be completed using a single mouse. 2-(4-Propylphenyl) propanoic acid was used as an internal standard. Standard curves for each enantiomer were linear from 0.04 to 80.00 μg/mL, demonstrating a lower limit of quantitation (LLOQ) than all previously reported methods. This method was completely validated and successfully executed to investigate the pharmacokinetics of ibuprofen enantiomers after intravenous administration of racemic ibuprofen, (S)-(+)-ibuprofen, and (R)-(−)-ibuprofen in Kunming mice, respectively. The results showed that the pharmacokinetic profiles of the (R)-(−)-ibuprofen and (S)-(+)-ibuprofen were significantly different, indicating the unidirectional inversion of R-(−)-ibuprofen to (S)-(+)-ibuprofen.