Semi-continuous and continuous processes for enantiomeric separation

Abstract

This review covers continuous preferential crystallization, membrane separation, chromatography, and other techniques identifying the environmental impact and highlighting what should be considered in future development.

Enhancement of separation performance for ofloxacin enantiomers by a biphasic recognition chiral extraction system

“…Therefore, the optical purity of chiral drugs is of great significance in their production 1,2 . The methods to obtain chiral drugs mainly include chiral pool synthesis, asymmetric synthesis, and chiral resolution 3–5 . Theoretically, synthesis methods could produce various enantiomeric drugs with high purity, but their high cost and long development periods limit their large‐scale industrial applications to some extent 6–8 .…”

“…1,2 The methods to obtain chiral drugs mainly include chiral pool synthesis, asymmetric synthesis, and chiral resolution. [3][4][5] Theoretically, synthesis methods could produce various enantiomeric drugs with high purity, but their high cost and long development periods limit their large-scale industrial applications to some extent. [6][7][8] In comparison, chiral resolution is more potential for industrialization and usually exists as a post-treatment process of synthesis.…”

Case of Chiral Resolution through Converting Two Racemic Compounds into a Conglomerate

“…Among the general methods of chiral resolution, crystallization-based enantioseparation, including classical resolution, preferential crystallization, and so on, is the most flexible and productive way that is easy to be applied on an industrial scale . In classical resolution, a racemic compound (∼90% racemates) is usually resolved by a chiral enantiomerical resolving agent to form diastereomeric salts. , However, only conglomerates (5–10% racemates) and some of the low-component eutectic point racemic compounds (to avoid excessive consumption of pure enantiomers) can be separated into enantiopure components by directly adding the seeds of preferential crystallization …”

“…7,8 However, only conglomerates (5−10% racemates) and some of the low-component eutectic point racemic compounds (to avoid excessive consumption of pure enantiomers) can be separated into enantiopure components by directly adding the seeds of preferential crystallization. 9 Fortunately, in recent years it has been found that a crystalline supramolecular assembly with two or more molecules, i.e., multicomponent crystals (salts, cocrystals, or solvates), has the potential to accomplish the chiral separation of two racemic compounds simultaneously. 10,11 Assuming that a couple of racemic compounds can interact with each other (Scheme 1), there are three possible distinct solid-phase compositions in heterogeneous equilibria.…”

Gating ion and fluid transport with chiral solvent

“…Chirality plays a fundamental role in life. There have been signicant efforts made to develop technologies to separate racemic mixtures to create enantiomerically pure samples [1][2][3] and to perform asymmetric synthesis 4 to provide enantiomerically pure product. Biological channels [5][6][7] and articial nanopores 8,9 have been used to create systems that can distinguish between enantiomeric analytes and to prepare ltration systems capable of transporting a single enantiomer with high selectivity.…”