Spontaneous Resolution in Racemic Solutions of N-trifluoroacetylated α-aminoalcohols

The spontaneous resolution was observed in the racemic solution of N-trifluoroacetylated α-aminoalcohol (TFAAA-6) in CCl4. In against other cases of the conglomerates formation, the TFAAA-6 forms highly anisometric crystalline structures (strings). Herewith, the spontaneous resolution was not observed in the racemic solution of TFAAA-5 in heptane, where the isometric precipitate was formed. The latter was also observed in the TFAAA-5 solutions in heptane with small enantiomeric excess (EE), down to 2 %. With that, the homochiral strings formed in the TFAAA-5 solutions in heptane with larger EEs. In this case, the strings formed from the excess of one of the enantiomers remained in solution after precipitation of the racemic residual. This process leads to the enhancement of chiral polarization in systems close to racemic and can explain the chiral purity of the living cell.

Development and Validation of a Reversed-Phase Chiral HPLC Method to Determine the Chiral Purity of Bulk Batches of (S)-Enantiomer in Afoxolaner

Afoxolaner is a new antiparasitic molecule from the isoxazoline family that acts on insect acarine g-aminobutyric acid and glutamate receptors. Afoxolaner is a racemic mixture, which has a chiral center at the isoxazoline ring. A reversed-phase chiral HPLC method has been developed to determine the chiral purity of bulk batches of (S)-enantiomer in afoxolaner for the first time. This method can also be used to verifythat afoxolaner is a racemic mixture, which was demonstrated by specific rotation. ChromSword, an artificial intelligence method development tool, was used for initial method development. The column selected for the final method was CHIRALPAK AD-RH (150 × 4.6 mm, 5 μm particle size), maintained at 45°C, and isocratic elution using water–isopropanol–acetonitrile (40 + 50 + 10, v/v/v) as the mobile phasewith a detection wavelength of 312 nm. The run time for the method was 11 min. The resolution and selectivity factors of the two enantiomers were 2.3 and 1.24, respectively. LOQ and LOD of the method were 1.6 and 0.8 μg/mL, respectively. This method was appropriately validated according to International Conference on Harmonization guidelines for its intended use.