(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.

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.

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.

L-3,4-dihydroxyphenylalanine (L-DOPA or Levodopa) is widely used to treat Parkinson's disease, but its large-scale chemical synthesis is costly and environmentally challenging. This study investigates the enzymatic conversion of L-tyrosine to L-Dopa to enhance efficiency and yield without any potential racemization. Tyrosinase, extracted from button mushrooms, was immobilized as cross-linked enzyme aggregates (TY CLEAs), achieving an activity of 31.32 units/g. Commercially available skim milk served as a protein feeder and demonstrated antioxidant properties, helping prevent the formation of L-dopachrome as a byproduct by inhibiting the sequential oxidation of L-dopaquinone, along with ascorbic acid as a reducing agent. We evaluated the stability of TY CLEAs under varying temperatures, pH levels, and organic solvents. High productivity of 1210.95 mgL-1 h-1 was achieved using 10 units of enzyme at a substrate concentration of 15 mM with the use of a surfactant.

Dibenzoyl-L-tartaric acid (L-DBTA) is a crucial compound in the synthesis of chiral molecules, particularly within the pharmaceutical industry. Ensuring the enantiomeric purity of L-DBTA is essential for regulatory compliance, quality control, and process optimization. To achieve this, a high-performance liquid chromatography (HPLC) method was developed and validated for determining the D-DBTA content in L-DBTA. The method validation adhered to ICH Q2(R2) guidelines, covering parameters such as system suitability, solution stability, robustness, linearity, range, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision. HPLC separation was performed using a Chiral PAK IA column (250 × 4.6 mm, 5.0 μm) with an isocratic mobile phase consisting of n-heptane, isopropanol (IPA), and trifluoroacetic acid (900:100:1 v/v/v). The column temperature was maintained at 40°C, and the sample cooler was kept at ambient conditions. Detection was carried out at 230 nm, achieving a resolution greater than 1.5 between L-DBTA and D-DBTA. The method demonstrated excellent linearity over a range of 30%-200% of the specification limit, with accuracy and range established from the LOQ level to 200%. Solution stability was confirmed for 1 day at room temperature, and precision was validated at both the LOQ and 100% levels. All validation parameters met the acceptance criteria, confirming the method's suitability for routine testing and batch release at quality control sites. This HPLC method is both sensitive and selective, ensuring the reliable determination of chiral purity in L-DBTA and its impurities.

No abstract is available for this article.

Magnetic circularly polarized luminescence (MCPL) spectroscopy is widely used to evaluate the luminescence dissymmetry factor (gMCPL) for compounds. However, even for the same instrument and operating conditions, the measured gMCPL is affected by errors associated with sources such as baseline drift and spectral noise, and so the range of variation of gMCPL must be considered when comparing values, which requires multiple measurements for the same sample. Also, because many samples undergo photodegradation under excitation light, it is difficult to accumulate and average spectra for samples with weak MCPL signals to improve the signal-to-noise ratio. Single measurements must therefore be performed on multiple samples and the results averaged. Furthermore, for samples with a small Stokes shift, spectral correction is required to compensate for the intensity reduction due to the inner-filter effect (IFE). Such measurements are generally performed manually and are therefore time consuming and prone to human error. Here, we demonstrate the use of a newly developed high-throughput MCPL system to automatically measure MCPL and fluorescence spectra of multiple samples of phthalocyanine complexes with high efficiency and reduced human errors. This system allows the incorporation of effective countermeasures to the issues of gMCPL variation, sample photodegradation, extremely weak MCPL signals, and the IFE.