Advancement of Chiral Resolution and Separations: Techniques and Applications

Abstract

Chirality, a ubiquitous phenomenon in nature, denotes the incapability of an entity to superimpose onto its mirror image. This property is inherently manifested in biological systems, where critical biomolecules such as DNA, enzymes, and proteins exist as chiral substances. Notably, proteins often demonstrate enantioselectivity towards their interacting partners, underscoring the critical role of chirality in drug-protein interactions. Consequently, the chirality of pharmaceutical agents significantly influences their efficacy and interaction with targeted proteins, necessitating a profound understanding and ability in chiral separation science to address challenges about chiral drug availability. Despite the complexity of enantiomer separation, the past few decades have witnessed substantial advancements in chiral resolution techniques. This article elucidates several pivotal methods: crystallization-based techniques, chromatographic separation, kinetic resolution, membrane-based separation, etc. Furthermore, the author spotlighted the application of chiral resolution methodologies at various drug research and development junctures, exemplified by a detailed case study on Sotorasib. This discourse aims to accentuate the burgeoning significance and the strides achieved in chiral resolution, paving the way for future innovative developments in this vital scientific domain.