Polysaccharide Derivatives as Unique Chiral Selectors for Enantioselective Chromatography

Abstract

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.

Comparative enantioseparation of chiral 4,4’-bipyridine derivatives on coated and immobilized amylose-based chiral stationary phases

“…Versatility, robustness and the highest loading capability among all other chiral supports make amylose and cellulose phenylcarbamate-based chiral stationary phases (CSPs) the most used for HPLC enantioseparation of chiral compounds [1]. These advantageous features are due to the structural peculiarities of these chiral supports where the polysaccharide derivative is coated or immobilized on the silica surface with high density of chiral selector molecules per unit surface [2,3]. The polysaccharide phenylcarbamate is arranged in a high-ordered secondary structure forming grooves and ravines containing both polar and hydrophobic regions which accommodate and discriminate enantiomers through an elevated number of noncovalent interaction options (Fig.…”

“…1a) [4][5][6]. The supramolecular structure of polysaccharide-based selectors impacts their chiral recognition ability, and for this rea son, the preparation of the CSP is a critical step [1,3]. In this regard, several studies published over time reported differences in chiral recognition ability of coated and covalently immobilized polysaccharide-based selectors [7][8][9][10][11][12].…”

“…Indeed, some covalent immobilization technologies require the use of under-derivatized polysaccharides in order to attach the selector to the silica surface. Actually, all the immobilization conditions produce chemical and/or physical alteration of the selector [3,12]. The study of properties, function, and mechanisms of chiral chromatographic systems involves expertise at the interface of analytical, physical and organic chemistry.…”

Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View

“…Recent examples include the separation of stable enantio-enriched POCOP-based planar chiral pincer complexes by crystallization [33] and the enantioseparation of metalaxyl racemate by SMB chromatography [34]. Among the separation approaches, enantioselective LC is a very promising technique that has attracted great attention from the pharmaceutical industry for the production scale of enantiomerically pure drugs [35][36][37].…”

“…If all these requirements are being met, the chromatographic preparative separation will afford the desired isolated enantiomers. Among the different types of CSPs, polysaccharide-based are the most used due to their versatility, high-loading capability, and enantiodiscrimination performance [36,40,41,51,52]. Despite the solvent limitation in mobile phase composition, the polysaccharide-based CSPs are compatible with normal, reversed, polar organic and polar ionic elution modes.…”