Polysaccharide Derivatives as Unique Chiral Selectors for Enantioselective Chromatography.

From the beginning of the 1980s, the life science industry increasingly recognized the importance of chirality in biological interaction processes, but the methods for preparing optically pure drugs were still limited. Most of the syntheses of chiral compounds were performed starting from optically active building blocks (chiral pool), mainly from natural sources, or by resolution of the enantiomers via formation of diastereomers. In this context, there was a growing interest for enantioselective processes, such as synthetic methodologies and separation techniques for accessing optically pure substances in an effective manner. Among the separation approaches, enantioselective chromatography looked very promising and a project aiming to explore this option was started in the Central Research Laboratories of former Ciba-Geigy. This article reviews the story of this development which culminated in the discovery of highly efficient polysaccharide-based chiral stationary phases which have now become the gold standard in the world of enantioselective chromatography. It shows also how the technique of enantioselective chromatography has evolved from an analytical tool to a practical preparative technology, up to production scale.

High-Performance Liquid Chromatographic Resolution of Neutral and Cationic Hetero[6]Helicenes.

Cationic hetero[6]helicenes 1+, 2+ and 3+ have been recently disclosed. Herein we report on their enantiomeric separation using high-performance liquid chromatography. Separation of the antipodes can be achieved in preparative scale on neutral adducts with Chiralcel OD-I or Chiralpak ID CSP. Selectivity factors of 1.90, 1.67, and 1.96 were obtained for 1-H, 2-H, and 3-H, respectively. Separation can also be performed on the carbenium ions on regular Chiralpak IA CSP using water-containing eluents, thus allowing for enantiomeric purity determinations in aqueous environments. Resolution of neutral and cationic helicenes is also achieved on more recently developed LARIHC columns. The versatility of the cyclofructan phases allows for baseline separations for both cases and their loading capabilities are demonstrated. Finally, the configurational stability of 1+, 2+, and 3+ was measured. For each replacement of an oxygen atom by an amino group, the racemization barrier increases significantly (ΔG‡ = 29.8, 36.3 and >37 kcal mol(-1) for 1+, 2+, and 3+ respectively).

Real-time assessment of enantiomeric purity via a polarimetric/absorption detector response function.

The development of methodology appropriate for the rapid and precise assessment of enantiomeric purity is a critical need in the life sciences with impact in a number of areas including biomedical research, biotechnology, and pharmaceutical science. Real-time assessment of enantiomeric purity is critical to decisions related to possible product purity and/or the need for, and the type of additional processing. Recently, we have shown that laser-based polarimetric detection, in combination with ultraviolet detection, can be used to assess enantiomeric purity in real-time as an adjunct to the separation process. A mass-independent response function is obtained from the ratio of the normalized polarimetric signal relative to the normalized UV signal. This response ratio will be shown to be equivalent to the enantiomeric excess and independent of concentration and chromatographic resolution. The methodology will be evaluated as a function of injected mass, enantiomeric excess, chromatographic resolution, and peak asymmetry.