A new chiral stationary phase based on noscapine: Synthesis, enantioseparation, and docking study

Noscapine is an isolated compound from the opium poppy, with distinctive chiral structure and chemistry, interacts with other compounds due to having multiple pi-acceptors, hydrogen bond acceptors, and ionic sites. Therefore, it has promising applicability for the enantioselective separation of a wide range of polar, acidic, basic, and neutral compounds. A new noscapine derivative chiral stationary phase (ND-CSP) has been synthesized by consecutive N-demethylation, reduction, and N-propargylation of noscapine followed by attachment of a solid epoxy-functionalized silica bed through the 1,3-dipolar Huisgen cycloaddition. The noscapine derivative-based stationary phase provides a considerable surface coverage, which is greater than some commercial CSPs and can validate better enantioresolution performance. The major advantages inherent to this chiral selector are stability, reproducibility after more than 200 tests, and substantial loading capacity. The characterization by Fourier transform infrared (FTIR) spectroscopy and elemental analysis indicated successful functionalization of the silica surface. Chromatographic method conditions like flow rate and mobile phase composition for enantioseparation of various compounds such as warfarin, propranolol, mandelic acid, and a sulfanilamide derivative were optimized. Comparing the experimental results with docking data revealed a clear correlation between the calculated binding energy of ND-CSP and each enantiomer with the resolution of enantiomer peaks.

Automated summary

Noscapine, a compound derived from opium poppy, shows potential for enantioselective separation of various compounds due to its distinctive chiral structure and chemistry. Researchers have synthesized a new noscapine derivative chiral stationary phase (ND-CSP) with better enantioresolution performance, stability, reproducibility, and loading capacity. This stationary phase provides a considerable surface coverage and has been successfully used for the enantioseparation of different compounds.